KLF4对内毒素所致炎症介质基因表达的调控及机制研究
|
摘要
脓毒症(sepsis)是由感染引起的全身炎症反应综合征(systemicinflammatory response syndrome,SIRS)。虽然其发生机制尚未完全阐明,但是革兰氏阴性细菌胞壁上的脂多糖(lipopolysacchride,LPS)即内毒素启动体内免疫系统在脓毒症发病中的重要性已受到广泛关注。LPS进入细胞内可激活多条信号转导通路,通过直接或间接的方式激活炎症相关转录因子,从而导致大量下游炎症介质基因的过度表达。
Kruppel样因子4(Kruppel-like factor 4,KLF4)是Sp1/KLF锌指转录因子家族的成员之一。KLF4能够与下游基因启动子区的GC盒,CACCC盒和基础转录元件(basic transcription elements)三种结合元件相结合,从而直接调控这些基因的表达。通过对下游基因表达的调控,KLF4在正常细胞的增殖和分化、胚胎发育以及肿瘤的发生发展过程中发挥重要作用。但是在LPS作用下KLF4呈何种表达模式,KLF4是否对LPS所致的炎症介质基因表达具有调控作用,以及KLF4如何发挥调控作用等问题,目前仍不清楚。本实验室近年采用cDNA微阵列检测了内毒素休克小鼠肺组织基因表达谱的变化,发现KLF4基因在注射内毒素2小时的小鼠肺组织中表达上调;在注射内毒素20小时后,表达水平进一步增高,达正常水平的10倍以上。以上结果提示,KLF4可能是一个在炎症反应中起重要作用的转录因子,它的表达改变可能参与了LPS诱导的炎症介质基因的表达调控。阐明KLF4在调控LPS所致的全身炎症反应中的生物学功能,对于揭示脓毒症的发生机制,进一步探讨其有效防治措施,可能具有重要意义。
为了观察KLF4在LPS作用下的表达模式,本研究第一部分采用人THP-1单核细胞、人U937单核巨噬细胞和小鼠RAW264.7巨噬细胞作为研究对象,采用RT-PCR和Western blot分别于mRNA和蛋白质水平检测KLF4在内毒素反应中的表达,发现LPS导致多种单核巨噬细胞中KLF4的表达显著增加,并呈时间与剂量依赖模式;在RAW264.7巨噬细胞中KLF4的表达在LPS刺激的早期(1-2 h)即明显增加,并且持续至晚期(24 h以后)。
为了观察KLF4是否对炎症介质基因具有调控作用,本研究第二部分首先构建了KLF4过表达的RAW264.7细胞株,并采用反义寡核苷酸技术建立了内源性KLF4表达抑制的模型;根据生物信息学对炎症介质基因启动子区的分析及RT-PCR的筛选结果,选取了两个具有代表性的早期炎症介质基因IL-1β和IL-10,观察了KLF4对这两个基因表达及释放的影响,并对其调控机制进行了探讨,获得了以下实验结果:(1)KLF4对LPS刺激下IL-1β和IL-10 mRNA表达水平的影响。正常状态下,细胞的IL-1βmRNA表达水平较低;LPS刺激之后,IL-1β的mRNA表达明显升高并在2 h时达到高峰,而KLF4过表达明显抑制了LPS诱导的IL-1βmRNA的表达;KLF4的过表达使IL-10 mRNA的基础表达增高,而LPS刺激之后,IL-10 mRNA的诱导表达显著高于空载体组。(2)KLF4对LPS刺激下IL-1β和IL-10蛋白质表达水平的影响。KLF4过表达能够抑制LPS诱导的IL-1β释放,促进IL-10的释放;而KLF4内源性抑制则促进IL-1β的释放,抑制IL-10的诱导释放。(3)LPS促进KLF4与IL-1β和IL-10基因启动子区的结合活性。在正常状态下KLF4能够与IL-1β基因启动子区-35～-6bp和IL-10基因启动子区-244～-215bp结合,LPS能够促进此结合活性的增强。(4)KLF4对LPS刺激下IL-1β和IL-10基因启动子转录活性的影响。KLF4能够抑制正常状态下IL-1β基因启动子的转录活性,并明显抑制LPS所致的IL-1β基因启动子转录活性的增强;KLF4能够激活正常状态下IL-10基因启动子的转录活性,促进LPS所致的IL-10基因启动子转录活性的增强。
由于KLF4的表达水平在LPS刺激的晚期(24 h以后)仍然升高明显,这提示KLF4可能对晚期炎症介质也具有调控作用。本文第三部分选取了晚期炎症介质HMGB1进行研究。结果发现:(1)KLF4能够促进HMGB1的基础表达,并促进LPS刺激下的HMGB1表达、移位及释放。(2)KLF4可以与HMGB1基因启动子区-736～-707bp和-1317～-1304bp结合,LPS能够促进其结合活性。
上述结果表明,KLF4通过抑制早期促炎介质IL-1β的表达与释放及促进早期抗炎介质IL-10的表达与释放可能在LPS所致的SIRS早期发挥抑炎作用;但通过促进晚期促炎介质HMGB1的表达、移位及释放可能在LPS所致的SIRS晚期发挥促炎作用。
综上所述,本研究发现了KLF4的一个新功能,即能够通过与某些炎症基因启动子区的KLF4结合元件相结合来直接调控这些基因的表达,并影响其释放。目前认为脓毒症发病机制的本质是失控性炎症反应,转录因子对各种炎症介质的调控起到了非常重要的作用。KLF4对LPS所致炎症反应的双向调节作用,为揭示脓毒症的发病机制提供了新的实验依据,也为深入探讨KLF4的生物学功能和脓毒症的防治提供了新的线索。
Sepsis is the systemic inflammatory response syndrome(SIRS) induced by infection.It has been emphasized that lipopolysaechride(LPS) plays important role in the pathogenesis of sepsis by initiating the immune system.Many studies have demonstrated that LPS mediates activation of multiple signal-transduction pathways and some inflammation-related transcriptional factors,and then promotes the expression of multiple target inflammatory genes.However,the particular mechanisms of sepsis are still obscure.
Kruppel-like factor 4(KLF4),a member of Sp1/KLF zinc-finger transcriptional factor family,binds to the binding sites including GC box, CACCC box and basic transcription elements on the promoters of target genes,to regulate the expression of target genes directly.By regulating the expression of the target genes,KLF4 plays important roles in cellular proliferation and differentiation,embryogenesis and the development of carcinoma.It is not delineated on the expression pattem of KLF4 under LPS treatment,and the roles and mechanisms of KLF4 in regulating the expression of inflammatory genes.Our previously research from cDNA microarray assays revealed that the expression level of KLF4 was up-regulated in lung tissues at 2 h,and further increased up to more than 10 times of the normal level at 20 h after LPS injection.These results indicate that KLF4 may be an important transcriptional factor participating in the expression regulation of inflammatory mediator genes induced by LPS.
To verify the hypothesis mentioned above,we first investigated the expression pattern of KLF4 in LPS-mediated inflammatory cell models in human THP-1 monoeytes,human U937 monocytes/macrophages and mouse RAW264.7 macrophages by RT-PCR and Western blot.The results showed that the expression of KLF4 was up-regulated obviously in all the three kinds of monoeytes/maerophages in a time and dose-dependent manner after exposure to LPS.Meanwhile,the expression of KLF4 in RAW264.7 maerophages was increased significantly at the early phase (within 1-2 h)and further increased up to the late phase(after 24 h)after LPS stimulation.
In order to understand the roles of KLF4 in regulating the expression of inflammatory mediator genes,we first overexpressed mouse KLF4 cDNA gene(pcDNA3.1-KLF4)into RAW264.7 macrophages by gene transfection and G418 screening,and inhibited the expression of KLF4 gene in RAW264.7 macrophages by transfection of KLF4 antisense oligonucleotides.Then,according to the screening results from bioinformatics and RT-PCR,we selected IL-1βand IL-10,two representative inflammatory mediator genes activated at early phase of inflammation,to investigate the effect of KLF4 on their expression and release under normal condition and LPS treatment.The results showed that,overexpression of KLF4 could inhibit the expression and release of IL-1βinduced by LPS,but promote the expression and release of IL-10 under the normal condition and after LPS stimulation;on the other hand, the inhibition of KLF4 by antisense oligonucleotides could promote the expression and release of IL-1β,and inhibit the expression and release of IL-10 under normal condition and after LPS stimulation.The results from EMSA demonstrated that KLF4 could bind to the KLF4 binding sites on the promoters of IL-1βand IL-10 genes,and the results from luciferase reporter gene assay demonstrated that KLF4 could inhibit the transcriptional activity of IL-1βgene and promote the transcriptional activity of IL- 10 gene.
According to the up-regulation of KLF4 at the late phase after LPS stimulation,we predicted that KLF4 might also regulate the inflammatory mediator gene activated at the late phase.Therefore,we investigated the effect of KLF4 on the expression and release of HMGB1,an important inflammatory mediator gene released at the late phase of inflammation. The results showed that the levels of HMGB1 mRNA and protein were up-regulated under normal condition after KLF4 over-expression;after LPS stimulation,KLF4 overexpression promoted the expression, translocation and release of HMGB1.EMSA showed that KLF4 could bind to the sites at -736～-707 bp and -1317～-1304 bp on the HMGB1 promoter,and the binding activity was promoted by LPS stimulation.
It is indicated that KLF4 plays a bidirectional role in the regulation of inflammation induced by LPS.It may play anti-inflammatory role at the early phase of SIRS induced by LPS by inhibiting the expression and release of early pro-inflammatory mediator IL-1βand promoting the expression and release of early anti-inflammatory mediator IL-10;and may play pro-inflammatory role at the late phase of SIRS induced by LPS by increasing the expression,translocation and release of late pro-inflammatory mediator HMGB1.
Taken together,the present studies suggest a novel function of KLF4, that is,KLF4 can bind to the KLF4 binding sites on the promoters of inflammatory mediator genes including IL-1β,IL-10 and HMGB1 to regulate the expression and release of these genes.The bidirectional regulating effects of KLF4 on early or late inflammatory mediators provide novel insights into the pathogenesis of sepsis,and also new clues and information for the studies on the biological functions of KLF4,and the prevention and treatment of sepsis.
Kruppel样因子4(Kruppel-like factor 4,KLF4)是Sp1/KLF锌指转录因子家族的成员之一。KLF4能够与下游基因启动子区的GC盒,CACCC盒和基础转录元件(basic transcription elements)三种结合元件相结合,从而直接调控这些基因的表达。通过对下游基因表达的调控,KLF4在正常细胞的增殖和分化、胚胎发育以及肿瘤的发生发展过程中发挥重要作用。但是在LPS作用下KLF4呈何种表达模式,KLF4是否对LPS所致的炎症介质基因表达具有调控作用,以及KLF4如何发挥调控作用等问题,目前仍不清楚。本实验室近年采用cDNA微阵列检测了内毒素休克小鼠肺组织基因表达谱的变化,发现KLF4基因在注射内毒素2小时的小鼠肺组织中表达上调;在注射内毒素20小时后,表达水平进一步增高,达正常水平的10倍以上。以上结果提示,KLF4可能是一个在炎症反应中起重要作用的转录因子,它的表达改变可能参与了LPS诱导的炎症介质基因的表达调控。阐明KLF4在调控LPS所致的全身炎症反应中的生物学功能,对于揭示脓毒症的发生机制,进一步探讨其有效防治措施,可能具有重要意义。
为了观察KLF4在LPS作用下的表达模式,本研究第一部分采用人THP-1单核细胞、人U937单核巨噬细胞和小鼠RAW264.7巨噬细胞作为研究对象,采用RT-PCR和Western blot分别于mRNA和蛋白质水平检测KLF4在内毒素反应中的表达,发现LPS导致多种单核巨噬细胞中KLF4的表达显著增加,并呈时间与剂量依赖模式;在RAW264.7巨噬细胞中KLF4的表达在LPS刺激的早期(1-2 h)即明显增加,并且持续至晚期(24 h以后)。
为了观察KLF4是否对炎症介质基因具有调控作用,本研究第二部分首先构建了KLF4过表达的RAW264.7细胞株,并采用反义寡核苷酸技术建立了内源性KLF4表达抑制的模型;根据生物信息学对炎症介质基因启动子区的分析及RT-PCR的筛选结果,选取了两个具有代表性的早期炎症介质基因IL-1β和IL-10,观察了KLF4对这两个基因表达及释放的影响,并对其调控机制进行了探讨,获得了以下实验结果:(1)KLF4对LPS刺激下IL-1β和IL-10 mRNA表达水平的影响。正常状态下,细胞的IL-1βmRNA表达水平较低;LPS刺激之后,IL-1β的mRNA表达明显升高并在2 h时达到高峰,而KLF4过表达明显抑制了LPS诱导的IL-1βmRNA的表达;KLF4的过表达使IL-10 mRNA的基础表达增高,而LPS刺激之后,IL-10 mRNA的诱导表达显著高于空载体组。(2)KLF4对LPS刺激下IL-1β和IL-10蛋白质表达水平的影响。KLF4过表达能够抑制LPS诱导的IL-1β释放,促进IL-10的释放;而KLF4内源性抑制则促进IL-1β的释放,抑制IL-10的诱导释放。(3)LPS促进KLF4与IL-1β和IL-10基因启动子区的结合活性。在正常状态下KLF4能够与IL-1β基因启动子区-35～-6bp和IL-10基因启动子区-244～-215bp结合,LPS能够促进此结合活性的增强。(4)KLF4对LPS刺激下IL-1β和IL-10基因启动子转录活性的影响。KLF4能够抑制正常状态下IL-1β基因启动子的转录活性,并明显抑制LPS所致的IL-1β基因启动子转录活性的增强;KLF4能够激活正常状态下IL-10基因启动子的转录活性,促进LPS所致的IL-10基因启动子转录活性的增强。
由于KLF4的表达水平在LPS刺激的晚期(24 h以后)仍然升高明显,这提示KLF4可能对晚期炎症介质也具有调控作用。本文第三部分选取了晚期炎症介质HMGB1进行研究。结果发现:(1)KLF4能够促进HMGB1的基础表达,并促进LPS刺激下的HMGB1表达、移位及释放。(2)KLF4可以与HMGB1基因启动子区-736～-707bp和-1317～-1304bp结合,LPS能够促进其结合活性。
上述结果表明,KLF4通过抑制早期促炎介质IL-1β的表达与释放及促进早期抗炎介质IL-10的表达与释放可能在LPS所致的SIRS早期发挥抑炎作用;但通过促进晚期促炎介质HMGB1的表达、移位及释放可能在LPS所致的SIRS晚期发挥促炎作用。
综上所述,本研究发现了KLF4的一个新功能,即能够通过与某些炎症基因启动子区的KLF4结合元件相结合来直接调控这些基因的表达,并影响其释放。目前认为脓毒症发病机制的本质是失控性炎症反应,转录因子对各种炎症介质的调控起到了非常重要的作用。KLF4对LPS所致炎症反应的双向调节作用,为揭示脓毒症的发病机制提供了新的实验依据,也为深入探讨KLF4的生物学功能和脓毒症的防治提供了新的线索。
Sepsis is the systemic inflammatory response syndrome(SIRS) induced by infection.It has been emphasized that lipopolysaechride(LPS) plays important role in the pathogenesis of sepsis by initiating the immune system.Many studies have demonstrated that LPS mediates activation of multiple signal-transduction pathways and some inflammation-related transcriptional factors,and then promotes the expression of multiple target inflammatory genes.However,the particular mechanisms of sepsis are still obscure.
Kruppel-like factor 4(KLF4),a member of Sp1/KLF zinc-finger transcriptional factor family,binds to the binding sites including GC box, CACCC box and basic transcription elements on the promoters of target genes,to regulate the expression of target genes directly.By regulating the expression of the target genes,KLF4 plays important roles in cellular proliferation and differentiation,embryogenesis and the development of carcinoma.It is not delineated on the expression pattem of KLF4 under LPS treatment,and the roles and mechanisms of KLF4 in regulating the expression of inflammatory genes.Our previously research from cDNA microarray assays revealed that the expression level of KLF4 was up-regulated in lung tissues at 2 h,and further increased up to more than 10 times of the normal level at 20 h after LPS injection.These results indicate that KLF4 may be an important transcriptional factor participating in the expression regulation of inflammatory mediator genes induced by LPS.
To verify the hypothesis mentioned above,we first investigated the expression pattern of KLF4 in LPS-mediated inflammatory cell models in human THP-1 monoeytes,human U937 monocytes/macrophages and mouse RAW264.7 macrophages by RT-PCR and Western blot.The results showed that the expression of KLF4 was up-regulated obviously in all the three kinds of monoeytes/maerophages in a time and dose-dependent manner after exposure to LPS.Meanwhile,the expression of KLF4 in RAW264.7 maerophages was increased significantly at the early phase (within 1-2 h)and further increased up to the late phase(after 24 h)after LPS stimulation.
In order to understand the roles of KLF4 in regulating the expression of inflammatory mediator genes,we first overexpressed mouse KLF4 cDNA gene(pcDNA3.1-KLF4)into RAW264.7 macrophages by gene transfection and G418 screening,and inhibited the expression of KLF4 gene in RAW264.7 macrophages by transfection of KLF4 antisense oligonucleotides.Then,according to the screening results from bioinformatics and RT-PCR,we selected IL-1βand IL-10,two representative inflammatory mediator genes activated at early phase of inflammation,to investigate the effect of KLF4 on their expression and release under normal condition and LPS treatment.The results showed that,overexpression of KLF4 could inhibit the expression and release of IL-1βinduced by LPS,but promote the expression and release of IL-10 under the normal condition and after LPS stimulation;on the other hand, the inhibition of KLF4 by antisense oligonucleotides could promote the expression and release of IL-1β,and inhibit the expression and release of IL-10 under normal condition and after LPS stimulation.The results from EMSA demonstrated that KLF4 could bind to the KLF4 binding sites on the promoters of IL-1βand IL-10 genes,and the results from luciferase reporter gene assay demonstrated that KLF4 could inhibit the transcriptional activity of IL-1βgene and promote the transcriptional activity of IL- 10 gene.
According to the up-regulation of KLF4 at the late phase after LPS stimulation,we predicted that KLF4 might also regulate the inflammatory mediator gene activated at the late phase.Therefore,we investigated the effect of KLF4 on the expression and release of HMGB1,an important inflammatory mediator gene released at the late phase of inflammation. The results showed that the levels of HMGB1 mRNA and protein were up-regulated under normal condition after KLF4 over-expression;after LPS stimulation,KLF4 overexpression promoted the expression, translocation and release of HMGB1.EMSA showed that KLF4 could bind to the sites at -736～-707 bp and -1317～-1304 bp on the HMGB1 promoter,and the binding activity was promoted by LPS stimulation.
It is indicated that KLF4 plays a bidirectional role in the regulation of inflammation induced by LPS.It may play anti-inflammatory role at the early phase of SIRS induced by LPS by inhibiting the expression and release of early pro-inflammatory mediator IL-1βand promoting the expression and release of early anti-inflammatory mediator IL-10;and may play pro-inflammatory role at the late phase of SIRS induced by LPS by increasing the expression,translocation and release of late pro-inflammatory mediator HMGB1.
Taken together,the present studies suggest a novel function of KLF4, that is,KLF4 can bind to the KLF4 binding sites on the promoters of inflammatory mediator genes including IL-1β,IL-10 and HMGB1 to regulate the expression and release of these genes.The bidirectional regulating effects of KLF4 on early or late inflammatory mediators provide novel insights into the pathogenesis of sepsis,and also new clues and information for the studies on the biological functions of KLF4,and the prevention and treatment of sepsis.
引文
1.Tjardes,T.,Neugebauer,E.Sepsis research in the next millennium:concentrate on the software rather than the hardware.Shock,2002,17(1):1-8
2.Angus,D.C.,Linde-Zwirble,W.T.,Lidicker,J.,Clermont,G.,Carcillo,J.,Pinsky,M.R.Epidemiology of severe sepsis in the United States:analysis of incidence,outcome,and associated costs of care.Crit Care Med,2001,29(7):1303-1310
3.Riedemann,N.C.,Guo,R.F.,Ward,P.A.The enigma of sepsis.J Clin Invest,2003,112(4):460-467
4.Wheeler,A.P.,Bernard,G.R.Treating patients with severe sepsis.N Engl J Med,1999,340(3):207-214
5.Cavaillon,J.M.,Annane,D.Compartmentalization of the inflammatory response in sepsis and SIRS.J Endotoxin Res,2006,12(3):151-170
6.Tracey,K.J.The inflammatory reflex.Nature,2002,420(6917):853-859
7.Martinon,F.,Tschopp,J.Inflammatory caspases and inflammasomes:master switches of inflammation.Cell Death Differ,2007,14(1):10-22
8.Hotchkiss,R.S.,Karl,I.E.The pathophysiology and treatment of sepsis.N Engl J Med,2003,348(2):138-150
9.Opal,S.M.,Gluck,T.Endotoxin as a drug target.Crit Care Med,2003,31(1Suppl):S57-64
10.Alexander,W.S.,Hilton,D.J.The role of suppressors of cytokine signaling(SOCS)proteins in regulation of the immune response.Annu Rev Immunol,2004,22503-529
11.Baeuerle,P.A.,Henkel,T.Function and activation of NF-kappa B in the immune system.Annu Rev Immunol,1994,12 141-179
12.Pahl,H.L.Activators and target genes of Rel/NF-kappaB transcription factors.Oncogene,1999,18(49):6853-6866
13.Guha,M.,Mackman,N.LPS induction of gene expression in human monocytes.Cell Signal,2001,13(2):85-94
14.Ye,X.,Liu,S.F.Lipopolysaccharide regulates constitutive and inducible transcription factor activities differentially in vivo in the rat.Biochem Biophys Res Commun,2001,288(4):927-932
15.Lee,E.G.,Boone,D.L.,Chai,S.,Libby,S.L.,Chien,M.,Lodolce,J.P.,Ma,A.Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.Science,2000,289(5488):2350-2354
16.Clark,R.B.The role of PPARs in inflammation and immunity.J Leukoc Biol,2002,71(3):388-400
17.Xiao,X.,Zuo,X.,Davis,A.A.,McMillan,D.R.,Curry,B.B.,Richardson,J.A.,Benjamin,I.J.HSF1 is required for extra-embryonic development,postnatal growth and protection during inflammatory responses in mice.Embo J,1999,18(21):5943-5952
18.Singh,I.S.,Viscardi,R.M.,Kalvakolanu,I.,Calderwood,S.,Hasday,J.D.Inhibition of tumor necrosis factor-alpha transcription in macrophages exposed to febrile range temperature.A possible role for heat shock factor-1 as a negative transcriptional regulator.J Biol Chem,2000,275(13):9841-9848
19.Xie,Y.,Chen,C.,Stevenson,M.A.,Auron,P.E.,Calderwood,S.K.Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6.J Biol Chem,2002,277(14):11802-11810
20.张华莉,刘瑛,王秋鹏,邓恭华,肖献忠.热休克反应和热休克转录因子1对LPS诱导的TNF-α和IL-15表达的影响.医学临床研究,2004,21(1):18-21
21.王秋鹏,张华莉,袁灿,刘瑛,肖卫民,王慷慨,刘双,于凤秀,肖献忠.热休克因子1对内毒素所致G-CSF基因表达的影响.中国生物化学与分子生物学报,2005,21(3):390-396
22.Bieker,J.J.Kruppel-like factors:three fingers in many pies.J Biol Chem,2001,276(37):34355-34358
23.Dang,D.T.,Pevsner,J.,Yang,V.W.The biology of the mammalian Kruppel-like family of transcription factors.Int J Biochem Cell Biol,2000,32(11-12):1103-1121
24.Lomberk,G.,Urrutia,R.The family feud:turning off Sp1 by Sp1-like KLF proteins.Biochem J,2005,392(Pt 1):1-11
25.Safe,S.,Abdelrahim,M.Sp transcription factor family and its role in cancer.Eur J Cancer,2005,41(16):2438-2448
26.Suzuki,T.,Aizawa,K.,Matsumura,T.,Nagai,R.Vascular implications of the Kruppel-like family of transcription factors.Arterioscler Thromb Vasc Biol,2005,25(6):1135-1141
27.Tone,M.,Powell,M.J.,Tone,Y.,Thompson,S.A.,Waldmann,H.IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3.J Immunol,2000, 165(1):286-291
28.Warke,V.G.,Nambiar,M.P.,Krishnan,S.,Tenbrock.,K.,Geller,D.A.,Koritschoner,N.P.,Atkins,J.L.,Farber,D.L.,Tsokos,G.C.Transcriptional activation of the human inducible nitric-oxide synthase promoter by Kruppel-like factor 6.J Biol Chem,2003,278(17):14812-14819
29.Luo,Q.,Ma,X.,Wahl,S.M.,Bieker,J.J.,Crossley,M.,Montaner,L.J.Activation and repression of interleukin-12 p40 transcription by erythroid Kruppel-like factor in macrophages.J Biol Chem,2004,279(18):18451-18456
30.SenBanerjee,S.,Lin,Z.,Atkins,G.B.,Greif,D.M.,Rao,R.M.,Kumar,A.,Feinberg,M.W.,Chen,Z.,Simon,D.I.,Luscinskas,F.W.,Michel,T.M.,Gimbrone,M.A.,Jr.,Garcia-Cardena,G.,Jain,M.K.KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation.J Exp Med,2004,199(10):1305-1315
31.Wu,J.,Lingrel,J.B.Kruppel-like factor 2,a novel immediate-early transcriptional factor,regulates IL-2 expression in T lymphocyte activation.J Immunol,2005,175(5):3060-3066
32.Das,H.,Kumar,A.,Lin,Z.,Patino,W.D.,Hwang,P.M.,Feinberg,M.W.,Majumder,P.K.,Jain,M.K.Kruppel-like factor 2(KLF2)regulates proinflammatory activation of monocytes.Proc Natl Acad Sci U S A,2006,103(17):6653-6658
33.Chanchevalap,S.,Nandan,M.O.,McConnell,B.B.,Charrier,L.,Merlin,D.,Katz,J.P.,Yang,V.W.Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells.Nucleic Acids Res,2006,34(4):1216-1223
34.Conkright,M.D.,Wani,M.A.,Anderson,K.P.,Lingrel,J.B.A gene encoding an intestinal-enriched member of the Kruppel-like factor family expressed in intestinal epithelial cells.Nucleic Acids Res,1999,27(5):1263-1270
35.Atkins,G.B.,Jain,M.K.Role of Kruppel-like transcription factors in endothelial biology.Circ Res,2007,100(12):1686-1695
36.Cho,Y.G.,Song,J.H.,Kim,C.J.,Nam,S.W.,Yoo,N.J.,Lee,J.Y.,Park,W.S.Genetic and epigenetic analysis of the KLF4 gene in gastric cancer.Apmis,2007,115(7):802-808
37.McConnell,B.B.,Ghaleb,A.M.,Nandan,M.O.,Yang,V.W.The diverse functions of Kruppel-like factors 4 and 5 in epithelial biology and pathobiology.Bioessays,2007,29(6):549-557
38.Zhao,W.,Hisamuddin,I.M.,Nandan,M.O.,Babbin,B.A.,Lamb,N.E.,Yang,V.W.Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402
39.Ohnishi,S.,Ohnami,S.,Laub,F.,Aoki,K.,Suzuki,K.,Kanai,Y.,Haga,K.,Asaka,M.,Ramirez,F.,Yoshida,T.Downregulation and growth inhibitory effect of epithelial-type Kruppel-like transcription factor KLF4,but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256
40.Segre,J.A.,Bauer,C.,Fuchs,E.K1f4 is a transcription factor required for establishing the barrier function of the skin.Nat Genet,1999,22(4):356-360
41.Yuan,K.,Zhao,Z.,Liu,Y.,Zou,J.,Liu,M.,Chen,G.,You,J.,Xiao,X.A Study on the Changes of Gene Expression Profiles in Lung Tissues during Endotoxic Shock using cDNA Microarray.Progress in Biochemistry and Biophysics,2001,3402-406
42.Feinberg,M.W.,Cao,Z.,Wara,A.K.,Lebedeva,M.A.,Senbanerjee,S.,Jain,M.K.Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages.J Biol Chem,2005,280(46):38247-38258
43.Okano,J.,Opitz,O.G.,Nakagawa,H.,Jenkins,T.D.,Friedman,S.L.,Rustgi,A.K.The Kruppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact.FEBS Lett,2000,473(1):95-100
44.Hinnebusch,B.F.,Siddique,A.,Henderson,J.W.,Malo,M.S.,Zhang,W.,Athaide,C.P.,Abedrapo,M.A.,Chen,X.,Yang,V.W.,Hodin,R.A.Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor.Am J Physiol Gastrointest Liver Physiol,2004,286(1):G23-30
45.Chen,Z.Y.,Stile,J.L.,Tseng,C.C.Gut-enriched Kruppel-like factor represses omithine decarboxylase gene expression and functions as checkpoint regulator in colonic cancer cells.J Biol Chem,2002,277(48):46831-46839
46.Shie,J.L.,Chen,Z.Y.,Fu,M.,Pestell,R.G.,Tseng,C.C.Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976
47.Rowland,B.D.,Peeper,D.S.KLF4,p21 and context-dependent opposing forces in cancer.Nat Rev Cancer,2006,6(1):11-23
48.Wei,D.,Gong,W.,Kanai,M.,Schlunk,C.,Wang,L.,Yao,J.C.,WU,T.T.,Huang,S.,Xie,K.Drastic down-regulation of Kruppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65(7):2746-2754
49.Wei,D.,Kanai,M.,Huang,S.,Xie,K.Emerging role of KLF4 in human gastrointestinal cancer.Carcinogenesis,2006,27(1):23-31
50.Zhang,W.,Chen,X.,Kato,Y.,Evans,P.M.,Yuan,S.,Yang,J.,Rychahou,P.G,Yang,V.W.,He,X.,Evers,B.M.,Liu,C.Novel cross talk of Kruppel-like factor 4and beta-catenin regulates normal intestinal homeostasis and tumor repression.Mol Cell Biol,2006,26(6):2055-2064
51.Chen,Z.Y.,Shie,J.L.,Tseng,C.C.STAT1 is required for IFN-gamma-mediated gut-enriched Kruppel-like factor expression.Exp Cell Res,2002,281(1):19-27
52.Nickenig,G.,Baudler,S.,Muller,C.,Werner,C.,Werner,N.,Welzel,H.,Strehlow,K.,Bohm,M.Redox-sensitive vascular smooth muscle cell proliferation is mediated by GKLF and Id3 in vitro and in vivo.Faseb J,2002,16(9):1077-1086
53.Wang,H.,Bloom,O.,Zhang,M.,Vishnubhakat,J.M.,Ombrellino,M.,Cbe,J.,Frazier,A.,Yang,H.,Ivanova,S.,Borovikova,L.,Manogue,K.R.,Faist,E.,Abraham,E.,Andersson,J.,Andersson,U.,Molina,P.E.,Abumrad,N.N.,Sama,A.,Tracey,K.J.HMG-1 as a late mediator of endotoxin lethality in mice.Science,1999,285(5425):248-251
54.Cinel,I.,Dellinger,R.P.Advances in pathogenesis and management of sepsis.Curr Opin Infect Dis,2007,20(4):345-352
55.Nguyen,H.B.,Smith,D.Sepsis in the 21st century:recent definitions and therapeutic advances.Am J Emerg Med,2007,25(5):564-571
56.Liu,Y.,Sinha,S.,Owens,G.A transforming growth factor-beta control element required for SM alpha-actin expression in vivo also partially mediates GKLF-dependent transcriptional repression.J Biol Chem,2003,278(48):48004-48011
57.Dinarello,C.A.Interleukin-lbeta.Crit Care Med,2005,33(12 Suppl):S460-462
58.Li,J.,Moran,T.,Swanson,E.,Julian,C.,Harris,J.,Bonen,D.K.,Hedl,M.,Nicolae,D.L.,Abraham,C.,Cho,J.H.Regulation of IL-8 and IL-1beta expression in Crohn's disease associated NOD2/CARD15 mutations.Hum Mol Genet,2004,13(16):1715-1725
59.Lapinet,J.A.,Seapini,P.,Calzetti,F.,Perez,O.,Cassatella,M.A.Gene expression and production of tumor necrosis factor alpha,interleukin-1beta(IL-lbeta),IL-8,macrophage inflammatory protein 1alpha(MIP-1alpha),MIP-1beta,and gamma interferon-inducible protein 10 by human neutrophils stimulated with group B meningococcal outer membrane vesicles.Infect Immun,2000,68(12):6917-6923
60.Lee,C.,Lim,H.K.,Sakong,J.,Lee,Y.S.,Kim,J.R.,Baek,S.H.Janus kinase-signal transducer and activator of transcription mediates phosphatidic acid-induced interleukin(IL)-1beta and IL-6 production.Mol Pharmacol,2006,69(3):1041-1047
61.Sung,C.S.,Wong,C.S.Cellular mechanisms of neuroinflammatory pain:the role of interleukin-1beta.Acta Anaesthesiol Taiwan,2007,45(2):103-109
62.Moore,K.W.,de Waal Malefyt,R.,Coffman,R.L.,O'Garra,A.Interleukin-10 and the interleukin-10 receptor.Annu Rev Immunol,2001,19 683-765
63.Oberholzer,A.,Oberholzer,C.,Moldawer,L.L.Interleukin-10:a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug.Crit Care Med,2002,30(1 Suppl):S58-63
64.Pestka,S.,Krause,C.D.,Sarkar,D.,Walter,M.R.,Shi,Y.,Fisher,P.B.Interleukin-10 and related cytokines and receptors.Annu Rev Immunol,2004,22929-979
65.Kuhn,R.,Lohler,J.,Rennick,D.,Rajewsky,K.,Muller,W.Interleukin-10-deficient mice develop chronic enterocolitis.Cell,1993,75(2):263-274
66.Wunder,C.,Eichelbronner,O.,Roewer,N.Are ILo6,IL-10 and PCT plasma concentrations reliable for outcome prediction in severe sepsis7 A comparison with APACHE Ⅲ and SAPS Ⅱ.lnflamm Res,2004,53(4):158-163
67.Wang,H.,Vishnubhakat,J.M.,Bloom,O.,Zhang,M.,Ombrellino,M.,Sama,A.,Tracey,K.J.Proinflammatory cytokines(tumor necrosis factor and interleukin 1)stimulate release of high mobility group protein-1 by pituicytes.Surgery,1999,126(2):389-392
68.Rendon-Mitchell,B.,Ochani,M.,Li,J.,Han,J.,Wang,H.,Yang,H.,Susarla,S.,Czura,C.,Mitchell,R.A.,Chen,G,Sama,A.E.,Tracey,K.J.,Wang,H.IFN-gamma induces high mobility group box 1 protein release partly through a TNF-dependent mechanism.J Immunol,2003,170(7):3890-3897
69.Tang,D.,Shi,Y.,Kang,R.,Li,T.,Xiao,W.,Wang,H.,Xiao,X.Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1.J Leukoc Biol,2007,81(3):741-747
70.Lotze,M.T.,Tracey,K.J.High-mobility group box 1 protein(HMGB1):nuclear weapon in the immune arsenal.Nat Rev Immunol,2005,5(4):331-342
71.Wang,H.,Yang,H.,Czura,C.J.,Sama,A.E.,Tracey,K.J.HMGB1 as a late mediator of lethal systemic inflammation.Am J Respir Crit Care Med,2001,164(10 Pt 1):1768-1773
72.Czura,C.J.,Tracey,K.J.Targeting high mobility group box 1 as a late-acting mediator of inflammation.Crit Care Med,2003,31(1 Suppl):S46-50
73.Fang,W.H.,Yao,Y.M.,Shi,Z.G.,Yu,Y.,Wu,Y.,Lu,L.R.,Sheng,Z.Y.The significance of changes in high mobility group-1 protein mRNA expression in rats after thermal injury.Shock,2002,17(4):329-333
74.Scaffidi,P.,Misteli,T.,Bianchi,M.E.Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.Nature,2002,418(6894):191-195
75.Tsung,A.,Sahai,R.,Tanaka,H.,Nakao,A.,Fink,M.P.,Lotze,M.T.,Yang,H.,Li,J.,Tracey,K.J.,Geller,D.A.,Billiar,T.R.The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion.J Exp Meal,2005,201(7):1135-1143
76.Erlandsson Harris,H.,Andersson,U.Mini-review:The nuclear protein HMGB1as a proinflammatory mediator.Eur J Immunol,2004,34(6):1503-1512
77.Harris,H.E.,Raucci,A.Alarmin(g)news about danger:workshop on innate danger signals and HMGB1.EMBO Rep,2006,7(8):774-778
78.Mantell,L.L.,Parrish,W.R.,Ulloa,L.Hmgb-1 as a therapeutic target for infectious and inflammatory disorders.Shock,2006,25(1):4-11
79.Parrish,W.,Ulloa,L.High-mobility group box-1 isoforms as potential therapeutic targets in sepsis.Methods Mol Biol,2007,361 145-162
80.Yamada,S.,Maruyama,I.HMGB1,a novel inflammatory cytokine.Clin Chim Acta,2007,375(1-2):36-42
81.Yang,H.,Wang,H.,Czura,C.J.,Tracey,K.J.The cytokine activity of HMGB1.J Leukoc Biol,2005,78(1):1-8
82.Hunter,P.Sepsis under siege:a new understanding of sepsis might lead to the development of therapies to treat septic shock.EMBO Rep,2006,7(7):667-669
83.Hamik,A.,Lin,Z.,Kumar,A.,Balcells,M.,Sinha,S.,Katz,J.,Feinberg,M.W.,Gerzsten,R.E.,Edelman,E.R.,Jain,M.K.Kruppel-like factor 4 regulates endothelial inflammation.J Biol Chem,2007,282(18):13769-13779
[1]Dynan WS,Tjian R.The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter.Cell,35:79-87.
[2]Kadonaga JT,Carner KR,Masiarz FR,et al.Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain.Cell,51:1079-1090.
[3]Turner J,Crossley M.Mammalian Kruppel-like transcription factors:more than just a pretty finger.Trends Biochem Sci,24:236-240.
[4]Black AR,Black JD,Azizkhan-Clifford J.Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer.J Cell Physiol,188:143-160.
[5]Dang DT,Pevsner J,Yang VW.The biology of the mammalian Kruppel-like family of transcription factors.Int J Biochem Cell Biol,32:1103-1121.
[6]Bieker JJ.Kruppel-like factors:three fingers in many pies.J Biol Chem,276:34355-34358.
[7]Cook T,Gebelein B,Urrutia R.Spl and its likes:biochemical and functional predictions for a growing family of zinc finger transcription factors.Ann NY Acad Sci,880:94-102.
[8]Philipsen S,Suske G.A tale of three fingers:the family of mammalian Sp/XKLF transcription factors.Nucleic Acids Res,27:2991-3000.
[9]Suske G.The Sp-family of transcription factors.Gene,238:291-300.
[10]Oates AC,Pratt SJ,Vail B,et al.The zebrafish klf gene family.Blood,2001,98:1792-1801.
[11]Patel NH,Prince V.Beyond the Hox complex.Genome Biol,1:reviews 1027.1-1027.4.
[12]Ferrier DE,Holland PW.Ancient origin of the Hox gene cluster.Nat Rev Genet,2:33-38.
[13]Eichler EE,Hoffman SM,Adamson AA,et al.Complex beta-satellite repeat structures and the expansion of the zinc finger gene cluster in 19p12.Genome Res,8:791-808.
[14]Song C-Z,Keller K,Murata K.et al.Functional interaction between coactivators CBP/p300,PCAF,and transcription factor FKLF2.J Biol Chem,277:7029-7036.
[15]Zhang W,Kadam S,Emerson BM,et al.Site-specific acetylation by p300 or CREB binding protein regulates erythroid Kruppel-like factor transcriptional activity via its interaction with the SWI-SNF complex.Mol Cell Biol,21:2413-2422.
[16]Shields JM,Yang VW.Two potent nuclear localization signals in the gut-enriched Kruppel-like factor define a subfamily of closely related Kruppel proteins.J Biol Chem,272:18504-18507.
[17]Song A,Patel A,Thamatrakoln K,et al.Functional domains and DNA-binding sequences of RFLAT-1/KLF13,a Kruppel-like transcription factor of activated T lymphocytes.J Biol Chem,277:30055-30065.
[18]Wolfe SA,Neldudova L,Pabo CO.DNA recognition by Cys2His2 zinc finger proteins.Aunu Rev Biophys Biomol Struct,29:183-212.
[19]Elrod-Erickson M,Rould MA,Neldudova L,et al.Zif268 protein-DNA complex refined at 1.6 A:a model system for understanding zinc finger-DNA interactions.Structure,4:1171-1180.
[20]Kim CA,Berg JM.A resolution crystal structtLre of a designed zinc finger protein bound to DNA.Nat Struct Biol,3:940-945.
[21]Narayan VA,Kriwacki RW,Caradonna JP.Structures of zinc finger domains from transcription factor Sp1.Insights into sequence-specific protein-DNA recognition.J Biol Chem,272:7801-7809.
[22]Cook T,Gebelein B,Mesa K,et al.Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth.J Biol Chem,273:25929-25936.
[23]Kaczynski J,Zhang J-S,Ellenfieder V,et al.The Spl-like protein BTEB3inhibits transcription via the BTE box by interacting with mSin3A and HDAC-1co-repressors and competing with Sp1.J Biol Chem,276:36749-36756.
[24]Sogawa K,Kikuchi Y,Imataka H,et al.Comparison of DNA binding properties between BTEB1 and Sp1.J Biochem,114:605-609.
[25]Hagen G,Muller S,Beato M,et al.Cloning by recognition site screening of two novel GT box binding proteins:a family of Sp1 related genes.Nucleic Acids Res,20:5519-5525.
[26]Kingsley C,Winoto A.Cloning of GT box-binding proteins:a novel Sp1multigene family regulating T-cell receptor gene expression.Mol Cell Biol,12:4251-4261.
[27]Ryu S,Zhou S,Ladurner AG,et al.The transcriptional cofactor complex CRSP is required for activity of the enhancerbinding protein Sp1.Nature,397:446-450.
[28]Cook T,Gebelein B,Belal M,et al.Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins.J Biol Chem,274:29500-29504.
[29]Zhang JS,Moncrieffe MC,Kaczynski J,et al.A conserved alpha-helieal motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.Mol Cell Biol,21:5041-5049.
[30]Gill G,Pascal E,Tseng ZH,et al.A glutamine-rich hydrophobic patch in transcription factor Sp1 contacts the dTAFⅡ110 component of the Drosophila TFⅡD complex and mediates transcriptional activation.Proc Natl Acad Sci,91:192-196.
[31]Van Vliet J,Turner J,Crossley M.Human Kruppel-like factor 8:a CACCC-box binding protein that associates with CtBP and represses transcription.Nucleic Acids Res,28:1955-1962.
[32]Ellenrieder V,Zhang J-S,Kaczynski J,et al.Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2,an Sp1-like repressor.EMBO J,21:2451-2460.
[33]Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest.J Biol Chem,1996,271:20009-20017.
[34]Yet SF,McA'Nulty MM,Folta SC,et al.Human EZF,a Kruppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem,273:1026-1031.
[35]Basu P,Morris PE,Haar JL,et al.KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic beta-like globin genes in vivo. Blood,106(7):2566-2571.
[36]Katz JP,Perreault N,Goldstein BG,et al.The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon.Development,2002,129(11):2619-2628.
[37]Whitney EM,Ghaleb AM,Chen X,et al.Transcriptional profiling of the cell cycle checkpoint gene kruppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.Gene Expr,2006,13(2):85-96.
[38]Chen X,Whitney EM,Gao SY,et al.Transcriptional profiling of Kruppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.J Mol Biol,2003,326:665-677.
[39]Blanchon L,Nores R,Gallot D,et al.Activation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4 and Sp1.Biochem Biophys Res Commun,2006,343(3):745-753.
[40]Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Kruppel-like factor (Kruppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275:18391-18398.
[41]Jenkins TD,Opitz OG,Okano J,et al.Transactivation of the human keratin 4and Epstein-Barr virus ED-L2 promoters by gut-enriched Kruppel-like factor.J Biol Chem,1998,273:10747-10754.
[42]Shie JL,Chen ZY,Fu M,et al.Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28:2969-2976.
[43]Zhang W,Shields JM,Sogawa K,et al.The gut-enriched Kruppel-like factor suppresses the activity of the CYP1A1 promoter in an Sp1-dependent fashion.J Biol Chem,1998,273:17917-17925.
[44]Yoon HS,Yang VW.Requirement of Kruppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004,279:5035-5041.
[45]Yoon HS,Ghaleb AM,Nandan MO,et al.Kruppel-like factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage.Oncogene,2005,24(25):4017-4025.
[46]Segre JA,Bauer C,Fuchs E.Klf4 is a transcription factor required for establishing the barrier function of the skin.Nat Genet,1999,22:356-360.
[47]Brembeck FH,Rustgi AK.The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1.J Biol Chem,2000,275:28230-28239.
[48]Katz JP,Perreault N,Goldstein BG,et al.Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach.Gastroenterology,2005,128(4):935-945.
[49]Piccinni SA,Bolcato-Bellemin AL,Klein A,et al.Kruppel-like factors regulate the Lamal gene encoding the laminin alphal chain.J Biol Chem,2004,279:9103-9114.
[50]Gardiner MR,Daggett DF,Zon LI,et al.Zebrafish KLF4 is essential for anterior mesendoderm/pre-polster differentiation and hatching.Dev Dyn,2005,234(4):992-996.
[51]Li Y,McClintick J,Zhong L,et al.Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4.Blood,2005,105(2):635-637
[52]Chiefari E,Brunetti A,Arturi F,et al.Increased expression of AP2 and Sp1transcription factors in human thyroid tumours:a role in NIS expression regulation? BMC Cancer.2:35.
[53]Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23:395-402.
[54]Wei D,Gong W,Kanai M,et al.Drastic down-regulation of Kruppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65:2746-2754.
[55]Foster KW,Ren S,Louro ID,et al.Oncogene expression cloning by retroviral transduction of adenovirus E1Aimmortalized rat kidney RK3E cells:transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF.Cell Growth Differ,1999,10:423-434.
[56]Suzuki T,Shen H,Akagi K,et al.New genes involved in cancer identified by retroviral tagging.Nature Genet,2002,32:166-174.
[57]Foster KW,Liu Z,Nail CD,et al.Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia.Oncogene,2005,24:1491-1500.
[58]Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000,60:6488-6495.
[59]Pandya AY,Talley LI,Frost AR,et al.Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer.Clin Cancer Res,2004,10:2709-2719.
[60]Raman V,Martensen SA,Reisman D,et al.Compromised HOXA5 function can limit p53 expression in human breast tumors.Nature,2000,405:974-978.
[61]SenBanerjee S,Lin Z,Atkins GB,et al.KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation.J Exp Med.199:1305-1315.
[62]McCormick SM,Eskin SG,McIntire LV,et al.DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells.Proc Nail Acad Sci.98:8955-8960.
[63]Adam PJ,Regan CP,Hautmann MB,et al.Positive- and negativeacting Kruppel-like transcription factors bind a transforming growth factor beta control element required for expression of the smooth muscle cell differentiation marker SM22alpha in vivo.J Biol Chem.275:37798-37806.
[64]Liu Y,Sinha S,McDonald OG,et al.Kruppel-like factor 4 abrogates myocardin-induced activation of smooth muscle gene expression.J Biol Chem,280(10):9719-9727.
[65]Ai W,Liu Y,Langlois M,et al.Kruppel-like factor 4(KLF4)represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elementsJ Biol Chem,2004,279(10):8684-8693.
[66]Feinberg MW,Cao Z,Wara AK,et al.Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages.J Biol Chem,280(46):38247-38258.
[1]Nathalie Carayol,Alison Campbell,lsabelle Vachier,et al.Modulation of Cadherin and Catenins Expression by Tumor Necrosis Factor-α and Dexamethasone in Human Bronchial Epithelial Cells.Am J Respir Cell Mol Biol,2002,26:341-347.
[2]Sadikot,E.Duco Jansen,Blackwell,et al.High-Dose Dexamethasone Accentuates Nuclear Factor-κB Activation in Endotoxin-Treated Mice.Am J Respir Crit Care Med,2002,164:873-878.
[3]Tremblay LN,Slutsky AS.Ventilator-induced injury:from barotrauma to biotrauma.Proc Assoc Am Physicians,1998,110:482-488.
[4]Yi ES,Remick DG,Lim Y,et al.The intratracheal administration of endotoxin:X.Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo.Inflammation,1996,20:165-175.
[5]Pugin J,Dunn I,Jolliet P,et al.Activation of human macrophages by mechanical ventilation in vitro.Am J Physiol(Lung Cell Mol Physiol),1998,275:L1040-L1050.
[6]Avery B.Nathens,Richard Bitar,Christopher Davreux,et al.Pyrrolidine Dithiocarbamate Attenuates Endotoxin-induced Acute Lung Injury.Am J Respir Cell Mol Biol,1997,17:608-616.
[7]Pugin J,Verghese G,Widmer MC,et al.The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome.Crit Care Med,1999,27(2):304-312.
[8]Christman JW,Sadikot RT,Blackwell TS.The role of nuclear factor-kappa B in pulmonary diseases.Chest,2000,117(5):1482-1487.
[9]Papanicolaou DA,Wilder RL,Manolagas SC,et al.The pathophysiologic roles of interleukin-6 in human disease.Ann Intern Med,1998,128(2):127-137.
[10]Ranieri VM,Suter PM,Tortorella C,et al.Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome:a randomized controlled trial.JAMA,1999,282(1):54-61.
[11]William Y.Park,Richard B.Goodman,Kenneth P.Steinberg,et al.Cytokine Balance in the Lungs of Patients with Acute Respiratory Distress Syndrome.Am J Respir Crit Care Med,2001,164(10):1896-1903.
[12]Jurgen,Grzegorz,Anthony,et al.Critical Roles for Interleukin-4 and Interleuldn-5 during Respiratory Syncytial Virus Infection in the Development of Airway Hyper-responsiveness after Airway Sensitization.Am J Respir Crit Care Med,2000,162(2):380-386.
[13]James F.Chmiel,Michael W.Konstan,Jeannee.Knesebeck,et al.IL-10Attenuates Excessive Inflammation in Chronic Pseudomonas Infection in Mice.Am J Respir Crit Care Meal,2002,160:2040-2047.
[14]Shanley,T.P.,H.Schmal,H.P.Friedl,et al.Regulatory effects of intrinsic IL-10 in IgG immune complex- induced lung injury.J Immunol,1995,154:3454-3460.
[15]Bolger AP,Sharma R,Von Haeling S,et al.Effect of interlukin-10 on the production of tumor necrosis factor-α by peripheral blood mononuclear cells from patients with chronic heart failure.Am J Cardiol,2002,90(4):384-389.
[16]Lo CJ,Fu M,Cryer HG.Interleukin l0 inhibits alveolar macrophage production of inflammatory mediators involved in adult respiratory distress syndrome.J Surg Res,1998,79(2):179-184.
[17]Li Qi,Qian Guisheng,Zhang Qing,et al.The change in IL-13 mRNA expression in rat lungs with acute pulmonary injury induced big lipopolysaccharide.Chin J Burns,2002,18(3):145-148.
[18]Ashwood P,Harvey R,Verjee T,et al.Functional interactions between mucosal IL-1,IL-ra and TGF-beta 1 in ulcerative colitis.Inflamm Res,2004,53:53-59.
[19]Mitsuyama K,Tomiyasu N,Suzuki A,et al.A form of circulating interleukin-6receptor component soluble gp130 as a potential interleukin-6 inhibitor in inflammatory bowel disease.Clin Exp Immunol,2006,143(1):125-131.
[20]Monteleone G,Parrello T,Luzza F,et al.Response of human intestinal lamina additive effects of interleukin 15 and 7.Gut,1998,43:620.
[21]Furuya D,Yagihashi A,Komsysu M,et al.Serum interleukin-18 concentrations in patients with inflammatory bowel disease.J Immunother,2002,(suppl):565.
[22]Aizawa Y,Sutoh S,Matsuoka M,et al.Association of interleukin-18 gene single-nucleotidepolymorphisms with susceptibility to inflammatory bowel disease.Tissue Antigens,2005,65:88-92.
[23]Lindsay JO,Ciesielski CJ,Scheinin T,et al.Local delivery of adenoviral vectors encodingmurine interleukin 10 induces colonic interleukin 10production and is therapeutic for murine colitis.Gut,2003,52:981-987.
[24]Melgar S,YeungMM,Bas A,et al.Overexpression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis.Clin Exp Immunol,2003,134:127-137.
[25]Kadivar K,Ruchelli ED,Markowitz JE,et al.Intestinal interleukin-13 in pediatric inflammatory bowel disease patients.Inflamm Bowel Dis,2004,10(5):593-598.
[26]Fuss IJ,Heller F,Boirivant M,et al.Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis.J Clin Invest,2004,113:1490-1497.
[27]蒋明,DAVID YU,林孝义,等.中华风湿病学.北京:华夏出版社,2004:771-824.
[28]Dayer JM.The pivotal role of interleukin in the clinical manifestations of rheumatoid arthritis.Rheumatology,2003,42(suppl 2):3-10.
[29]Lee DM,Weinblatt ME.Rheumatoid Arthritis.Lancet,2001,358(9258):903-911.
[30]Abramson SB,Amin A.Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage.Rheumatology,2002,41(9):972-980.
[31]Tanaka M,Harigai M,Kawaguchi Y,et al.Mature form of interleukin 18 is expressed in rheumatoid arthritis synovial tissue and contributes to interferon-γproduction by synovial cells.J Rheumatol,2001,28(8):1779-1787.
[32]Yamamura M,Kawashima M,Taniai M,et al.Interferon-γ-inducing activity of interleukin-18 in the joint with rheumatoid arthritis.Arthritis Rheum,2001,44(2):275-285.
[33]Olee T,Hashimoto S,Quach J,et al.IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses.J Immunol,1999,162(2):1096-1100.
[34]Mcinnesi B,Al-Mughales J,FIELD M,et al.The role of interleukin-15 in T cell migration and activation in rheumatoid arthritis.Nat Med,1996,2(2):175-182.
[35]Ziolkowsk AM,Ko CA,Luszczykiewicz G,et al.High levels of IL-17 in rheumatoid arthritis patients:IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism.J Immunol,2000,164(5):2832-2838.
[36]Kurowsk AM,Rudnick AW,Kontny E,et al.Fibroblast-like synoviocytes from rheumatoid arthritis patients express functional IL-15 receptor complex:endogenous IL-15 in autocrine fashion enhances cell proliferation and expression of Bcl-xl and Bcl-2.J Immunol,2002,169(4):1760-1767.
[37]Miyazawa K,Mori A,Yamamoto K,et al.Constitutive transcription of the human interleukin-6 gene by rheumatoid synvoiocytes.Spontaneous activation of N F-κB and CBF1.Am J Pathol,1998,152(3):793-803.
[38]Atsumi T,Ishihara K,Kamimura D,et al.A point mutation of Tyr-759 in interleukin-6 family cytokine receptor subunit gp 130 causes autoimmune arthritis.J Exp Med,2002,196(7):979-990.
[39]Yashimoto T,Nagai N,Ohkusu K,et al.LPS-stimulated SJL macrophages produce IL-12 and IL-18 that inhabit IgE production in vitro by induction of IFN-gamma production from CD 3intIL-2R beta+ T cells.Immunol,1998,161(3):1483-1492.
[40]Lubberts E,Van denbersselaar L,Oppers-Walgreen B,et al.IL-17 promotes bone erosion in m urine collagen-induced arthritis through loss of the receptor activator of N F-Kb ligand / osteoprotegerin balance.J Immunol,2003,170(5):12655-12662.
[41]Chen XC,Xiao R.Investigation of ralve of rheumafoid factor and antikeratin antibody in diagnosing Rheumafoid arthritis.China Journal of Modem Medicine,2005,15(8):1265-1268.
[42]胡森,姚永明.脓毒症和全身炎症反应综合征.北京:科学出版社,1999.
[43]Nakamura T,Kawagoe Y,Suzuki T,et al.Changes in plasma interleukin-18 by direct hemoperfusion with polymyxin B-immobilized fiber in patients with septic shock.Blood Purif,2005,23(6):417-420.
[44]Oberholzer A,Steckholzer U,Kurimoto M,et al.Interleukin-18 plasma levels are increased in patients with sepsis compared to severely injured patients.Shock,2001,16(6):411-414.
[45]Netea MG,Kullberg BJ,Verschueren I,et al.Interleukin-18 induces production of proinflammatory cytokines in mice:no intermediate role for the cytokines of the tumor necrosis factor family and interleukin-1β.Eur J Immunol,2000,30(10):3057-3060.
[46]Puren,AJ,Fantuzzi G,Cu Y,et al.Interleukin-18(IFN-γ inducing factor)induces IL-8 and IL-1β via TNF-α production from non-CD14 + human blood mononuclear cells.J Clin Investig,1998,101(3):711-721.
[47]Hoshino T,Wiltrout RH,Young HA.IL-18 is a potent coinducer of IL-13 in NK and T cells:a new potential role for IL-18 inmodulating the immune response.J Immunol,1999,162(9):5070-5077.
[48]Yoshimoto T,Tsutsui H,Tominaga K,et al.IL-18,although antiallergic when administered with IL-12,stimulates IL-4 and histamine release by basophils.Proc N atl Acad Sci USA,1999,96(24):13962-13966.
[49]Armstrong L,MillarAB.Relative p roduction of tumour necrosis factor alpha and interlerkin - 10 in adult resp irationg distress syndrome.Thorax,1997,52:442 - 446.
[50]Lo CJ,FuM,CryerHC,et al.Interukin-10,inhabits celveolar macrohage production of inflammatory mediator involved in adult respiratory distress syndrome.Journal of Surgical Research,1998,72:179-184.
[51]Takakuwa T,Endo S,Shirakura Y,et al.Interleukin-10 gene transfer imp roves the survival rate of mice inoculated with Escherichia coli.Crit Care Med,2000,132:383-390.
[52]Patel RT,Deen KI,Youngs D,et al.Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis.Br J Surg,1994,81(9):1036-1038.
[53]Bone RC.Immunologic dissonance:a continuing evolution in our understanding of the systemic inflammatory response syndrome(SIRS)and the multiple organ dysfuncion syndrome(MODS).Ann Intern Med,1996,125(8):680-687.
2.Angus,D.C.,Linde-Zwirble,W.T.,Lidicker,J.,Clermont,G.,Carcillo,J.,Pinsky,M.R.Epidemiology of severe sepsis in the United States:analysis of incidence,outcome,and associated costs of care.Crit Care Med,2001,29(7):1303-1310
3.Riedemann,N.C.,Guo,R.F.,Ward,P.A.The enigma of sepsis.J Clin Invest,2003,112(4):460-467
4.Wheeler,A.P.,Bernard,G.R.Treating patients with severe sepsis.N Engl J Med,1999,340(3):207-214
5.Cavaillon,J.M.,Annane,D.Compartmentalization of the inflammatory response in sepsis and SIRS.J Endotoxin Res,2006,12(3):151-170
6.Tracey,K.J.The inflammatory reflex.Nature,2002,420(6917):853-859
7.Martinon,F.,Tschopp,J.Inflammatory caspases and inflammasomes:master switches of inflammation.Cell Death Differ,2007,14(1):10-22
8.Hotchkiss,R.S.,Karl,I.E.The pathophysiology and treatment of sepsis.N Engl J Med,2003,348(2):138-150
9.Opal,S.M.,Gluck,T.Endotoxin as a drug target.Crit Care Med,2003,31(1Suppl):S57-64
10.Alexander,W.S.,Hilton,D.J.The role of suppressors of cytokine signaling(SOCS)proteins in regulation of the immune response.Annu Rev Immunol,2004,22503-529
11.Baeuerle,P.A.,Henkel,T.Function and activation of NF-kappa B in the immune system.Annu Rev Immunol,1994,12 141-179
12.Pahl,H.L.Activators and target genes of Rel/NF-kappaB transcription factors.Oncogene,1999,18(49):6853-6866
13.Guha,M.,Mackman,N.LPS induction of gene expression in human monocytes.Cell Signal,2001,13(2):85-94
14.Ye,X.,Liu,S.F.Lipopolysaccharide regulates constitutive and inducible transcription factor activities differentially in vivo in the rat.Biochem Biophys Res Commun,2001,288(4):927-932
15.Lee,E.G.,Boone,D.L.,Chai,S.,Libby,S.L.,Chien,M.,Lodolce,J.P.,Ma,A.Failure to regulate TNF-induced NF-kappaB and cell death responses in A20-deficient mice.Science,2000,289(5488):2350-2354
16.Clark,R.B.The role of PPARs in inflammation and immunity.J Leukoc Biol,2002,71(3):388-400
17.Xiao,X.,Zuo,X.,Davis,A.A.,McMillan,D.R.,Curry,B.B.,Richardson,J.A.,Benjamin,I.J.HSF1 is required for extra-embryonic development,postnatal growth and protection during inflammatory responses in mice.Embo J,1999,18(21):5943-5952
18.Singh,I.S.,Viscardi,R.M.,Kalvakolanu,I.,Calderwood,S.,Hasday,J.D.Inhibition of tumor necrosis factor-alpha transcription in macrophages exposed to febrile range temperature.A possible role for heat shock factor-1 as a negative transcriptional regulator.J Biol Chem,2000,275(13):9841-9848
19.Xie,Y.,Chen,C.,Stevenson,M.A.,Auron,P.E.,Calderwood,S.K.Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6.J Biol Chem,2002,277(14):11802-11810
20.张华莉,刘瑛,王秋鹏,邓恭华,肖献忠.热休克反应和热休克转录因子1对LPS诱导的TNF-α和IL-15表达的影响.医学临床研究,2004,21(1):18-21
21.王秋鹏,张华莉,袁灿,刘瑛,肖卫民,王慷慨,刘双,于凤秀,肖献忠.热休克因子1对内毒素所致G-CSF基因表达的影响.中国生物化学与分子生物学报,2005,21(3):390-396
22.Bieker,J.J.Kruppel-like factors:three fingers in many pies.J Biol Chem,2001,276(37):34355-34358
23.Dang,D.T.,Pevsner,J.,Yang,V.W.The biology of the mammalian Kruppel-like family of transcription factors.Int J Biochem Cell Biol,2000,32(11-12):1103-1121
24.Lomberk,G.,Urrutia,R.The family feud:turning off Sp1 by Sp1-like KLF proteins.Biochem J,2005,392(Pt 1):1-11
25.Safe,S.,Abdelrahim,M.Sp transcription factor family and its role in cancer.Eur J Cancer,2005,41(16):2438-2448
26.Suzuki,T.,Aizawa,K.,Matsumura,T.,Nagai,R.Vascular implications of the Kruppel-like family of transcription factors.Arterioscler Thromb Vasc Biol,2005,25(6):1135-1141
27.Tone,M.,Powell,M.J.,Tone,Y.,Thompson,S.A.,Waldmann,H.IL-10 gene expression is controlled by the transcription factors Sp1 and Sp3.J Immunol,2000, 165(1):286-291
28.Warke,V.G.,Nambiar,M.P.,Krishnan,S.,Tenbrock.,K.,Geller,D.A.,Koritschoner,N.P.,Atkins,J.L.,Farber,D.L.,Tsokos,G.C.Transcriptional activation of the human inducible nitric-oxide synthase promoter by Kruppel-like factor 6.J Biol Chem,2003,278(17):14812-14819
29.Luo,Q.,Ma,X.,Wahl,S.M.,Bieker,J.J.,Crossley,M.,Montaner,L.J.Activation and repression of interleukin-12 p40 transcription by erythroid Kruppel-like factor in macrophages.J Biol Chem,2004,279(18):18451-18456
30.SenBanerjee,S.,Lin,Z.,Atkins,G.B.,Greif,D.M.,Rao,R.M.,Kumar,A.,Feinberg,M.W.,Chen,Z.,Simon,D.I.,Luscinskas,F.W.,Michel,T.M.,Gimbrone,M.A.,Jr.,Garcia-Cardena,G.,Jain,M.K.KLF2 Is a novel transcriptional regulator of endothelial proinflammatory activation.J Exp Med,2004,199(10):1305-1315
31.Wu,J.,Lingrel,J.B.Kruppel-like factor 2,a novel immediate-early transcriptional factor,regulates IL-2 expression in T lymphocyte activation.J Immunol,2005,175(5):3060-3066
32.Das,H.,Kumar,A.,Lin,Z.,Patino,W.D.,Hwang,P.M.,Feinberg,M.W.,Majumder,P.K.,Jain,M.K.Kruppel-like factor 2(KLF2)regulates proinflammatory activation of monocytes.Proc Natl Acad Sci U S A,2006,103(17):6653-6658
33.Chanchevalap,S.,Nandan,M.O.,McConnell,B.B.,Charrier,L.,Merlin,D.,Katz,J.P.,Yang,V.W.Kruppel-like factor 5 is an important mediator for lipopolysaccharide-induced proinflammatory response in intestinal epithelial cells.Nucleic Acids Res,2006,34(4):1216-1223
34.Conkright,M.D.,Wani,M.A.,Anderson,K.P.,Lingrel,J.B.A gene encoding an intestinal-enriched member of the Kruppel-like factor family expressed in intestinal epithelial cells.Nucleic Acids Res,1999,27(5):1263-1270
35.Atkins,G.B.,Jain,M.K.Role of Kruppel-like transcription factors in endothelial biology.Circ Res,2007,100(12):1686-1695
36.Cho,Y.G.,Song,J.H.,Kim,C.J.,Nam,S.W.,Yoo,N.J.,Lee,J.Y.,Park,W.S.Genetic and epigenetic analysis of the KLF4 gene in gastric cancer.Apmis,2007,115(7):802-808
37.McConnell,B.B.,Ghaleb,A.M.,Nandan,M.O.,Yang,V.W.The diverse functions of Kruppel-like factors 4 and 5 in epithelial biology and pathobiology.Bioessays,2007,29(6):549-557
38.Zhao,W.,Hisamuddin,I.M.,Nandan,M.O.,Babbin,B.A.,Lamb,N.E.,Yang,V.W.Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402
39.Ohnishi,S.,Ohnami,S.,Laub,F.,Aoki,K.,Suzuki,K.,Kanai,Y.,Haga,K.,Asaka,M.,Ramirez,F.,Yoshida,T.Downregulation and growth inhibitory effect of epithelial-type Kruppel-like transcription factor KLF4,but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256
40.Segre,J.A.,Bauer,C.,Fuchs,E.K1f4 is a transcription factor required for establishing the barrier function of the skin.Nat Genet,1999,22(4):356-360
41.Yuan,K.,Zhao,Z.,Liu,Y.,Zou,J.,Liu,M.,Chen,G.,You,J.,Xiao,X.A Study on the Changes of Gene Expression Profiles in Lung Tissues during Endotoxic Shock using cDNA Microarray.Progress in Biochemistry and Biophysics,2001,3402-406
42.Feinberg,M.W.,Cao,Z.,Wara,A.K.,Lebedeva,M.A.,Senbanerjee,S.,Jain,M.K.Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages.J Biol Chem,2005,280(46):38247-38258
43.Okano,J.,Opitz,O.G.,Nakagawa,H.,Jenkins,T.D.,Friedman,S.L.,Rustgi,A.K.The Kruppel-like transcriptional factors Zf9 and GKLF coactivate the human keratin 4 promoter and physically interact.FEBS Lett,2000,473(1):95-100
44.Hinnebusch,B.F.,Siddique,A.,Henderson,J.W.,Malo,M.S.,Zhang,W.,Athaide,C.P.,Abedrapo,M.A.,Chen,X.,Yang,V.W.,Hodin,R.A.Enterocyte differentiation marker intestinal alkaline phosphatase is a target gene of the gut-enriched Kruppel-like factor.Am J Physiol Gastrointest Liver Physiol,2004,286(1):G23-30
45.Chen,Z.Y.,Stile,J.L.,Tseng,C.C.Gut-enriched Kruppel-like factor represses omithine decarboxylase gene expression and functions as checkpoint regulator in colonic cancer cells.J Biol Chem,2002,277(48):46831-46839
46.Shie,J.L.,Chen,Z.Y.,Fu,M.,Pestell,R.G.,Tseng,C.C.Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976
47.Rowland,B.D.,Peeper,D.S.KLF4,p21 and context-dependent opposing forces in cancer.Nat Rev Cancer,2006,6(1):11-23
48.Wei,D.,Gong,W.,Kanai,M.,Schlunk,C.,Wang,L.,Yao,J.C.,WU,T.T.,Huang,S.,Xie,K.Drastic down-regulation of Kruppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65(7):2746-2754
49.Wei,D.,Kanai,M.,Huang,S.,Xie,K.Emerging role of KLF4 in human gastrointestinal cancer.Carcinogenesis,2006,27(1):23-31
50.Zhang,W.,Chen,X.,Kato,Y.,Evans,P.M.,Yuan,S.,Yang,J.,Rychahou,P.G,Yang,V.W.,He,X.,Evers,B.M.,Liu,C.Novel cross talk of Kruppel-like factor 4and beta-catenin regulates normal intestinal homeostasis and tumor repression.Mol Cell Biol,2006,26(6):2055-2064
51.Chen,Z.Y.,Shie,J.L.,Tseng,C.C.STAT1 is required for IFN-gamma-mediated gut-enriched Kruppel-like factor expression.Exp Cell Res,2002,281(1):19-27
52.Nickenig,G.,Baudler,S.,Muller,C.,Werner,C.,Werner,N.,Welzel,H.,Strehlow,K.,Bohm,M.Redox-sensitive vascular smooth muscle cell proliferation is mediated by GKLF and Id3 in vitro and in vivo.Faseb J,2002,16(9):1077-1086
53.Wang,H.,Bloom,O.,Zhang,M.,Vishnubhakat,J.M.,Ombrellino,M.,Cbe,J.,Frazier,A.,Yang,H.,Ivanova,S.,Borovikova,L.,Manogue,K.R.,Faist,E.,Abraham,E.,Andersson,J.,Andersson,U.,Molina,P.E.,Abumrad,N.N.,Sama,A.,Tracey,K.J.HMG-1 as a late mediator of endotoxin lethality in mice.Science,1999,285(5425):248-251
54.Cinel,I.,Dellinger,R.P.Advances in pathogenesis and management of sepsis.Curr Opin Infect Dis,2007,20(4):345-352
55.Nguyen,H.B.,Smith,D.Sepsis in the 21st century:recent definitions and therapeutic advances.Am J Emerg Med,2007,25(5):564-571
56.Liu,Y.,Sinha,S.,Owens,G.A transforming growth factor-beta control element required for SM alpha-actin expression in vivo also partially mediates GKLF-dependent transcriptional repression.J Biol Chem,2003,278(48):48004-48011
57.Dinarello,C.A.Interleukin-lbeta.Crit Care Med,2005,33(12 Suppl):S460-462
58.Li,J.,Moran,T.,Swanson,E.,Julian,C.,Harris,J.,Bonen,D.K.,Hedl,M.,Nicolae,D.L.,Abraham,C.,Cho,J.H.Regulation of IL-8 and IL-1beta expression in Crohn's disease associated NOD2/CARD15 mutations.Hum Mol Genet,2004,13(16):1715-1725
59.Lapinet,J.A.,Seapini,P.,Calzetti,F.,Perez,O.,Cassatella,M.A.Gene expression and production of tumor necrosis factor alpha,interleukin-1beta(IL-lbeta),IL-8,macrophage inflammatory protein 1alpha(MIP-1alpha),MIP-1beta,and gamma interferon-inducible protein 10 by human neutrophils stimulated with group B meningococcal outer membrane vesicles.Infect Immun,2000,68(12):6917-6923
60.Lee,C.,Lim,H.K.,Sakong,J.,Lee,Y.S.,Kim,J.R.,Baek,S.H.Janus kinase-signal transducer and activator of transcription mediates phosphatidic acid-induced interleukin(IL)-1beta and IL-6 production.Mol Pharmacol,2006,69(3):1041-1047
61.Sung,C.S.,Wong,C.S.Cellular mechanisms of neuroinflammatory pain:the role of interleukin-1beta.Acta Anaesthesiol Taiwan,2007,45(2):103-109
62.Moore,K.W.,de Waal Malefyt,R.,Coffman,R.L.,O'Garra,A.Interleukin-10 and the interleukin-10 receptor.Annu Rev Immunol,2001,19 683-765
63.Oberholzer,A.,Oberholzer,C.,Moldawer,L.L.Interleukin-10:a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug.Crit Care Med,2002,30(1 Suppl):S58-63
64.Pestka,S.,Krause,C.D.,Sarkar,D.,Walter,M.R.,Shi,Y.,Fisher,P.B.Interleukin-10 and related cytokines and receptors.Annu Rev Immunol,2004,22929-979
65.Kuhn,R.,Lohler,J.,Rennick,D.,Rajewsky,K.,Muller,W.Interleukin-10-deficient mice develop chronic enterocolitis.Cell,1993,75(2):263-274
66.Wunder,C.,Eichelbronner,O.,Roewer,N.Are ILo6,IL-10 and PCT plasma concentrations reliable for outcome prediction in severe sepsis7 A comparison with APACHE Ⅲ and SAPS Ⅱ.lnflamm Res,2004,53(4):158-163
67.Wang,H.,Vishnubhakat,J.M.,Bloom,O.,Zhang,M.,Ombrellino,M.,Sama,A.,Tracey,K.J.Proinflammatory cytokines(tumor necrosis factor and interleukin 1)stimulate release of high mobility group protein-1 by pituicytes.Surgery,1999,126(2):389-392
68.Rendon-Mitchell,B.,Ochani,M.,Li,J.,Han,J.,Wang,H.,Yang,H.,Susarla,S.,Czura,C.,Mitchell,R.A.,Chen,G,Sama,A.E.,Tracey,K.J.,Wang,H.IFN-gamma induces high mobility group box 1 protein release partly through a TNF-dependent mechanism.J Immunol,2003,170(7):3890-3897
69.Tang,D.,Shi,Y.,Kang,R.,Li,T.,Xiao,W.,Wang,H.,Xiao,X.Hydrogen peroxide stimulates macrophages and monocytes to actively release HMGB1.J Leukoc Biol,2007,81(3):741-747
70.Lotze,M.T.,Tracey,K.J.High-mobility group box 1 protein(HMGB1):nuclear weapon in the immune arsenal.Nat Rev Immunol,2005,5(4):331-342
71.Wang,H.,Yang,H.,Czura,C.J.,Sama,A.E.,Tracey,K.J.HMGB1 as a late mediator of lethal systemic inflammation.Am J Respir Crit Care Med,2001,164(10 Pt 1):1768-1773
72.Czura,C.J.,Tracey,K.J.Targeting high mobility group box 1 as a late-acting mediator of inflammation.Crit Care Med,2003,31(1 Suppl):S46-50
73.Fang,W.H.,Yao,Y.M.,Shi,Z.G.,Yu,Y.,Wu,Y.,Lu,L.R.,Sheng,Z.Y.The significance of changes in high mobility group-1 protein mRNA expression in rats after thermal injury.Shock,2002,17(4):329-333
74.Scaffidi,P.,Misteli,T.,Bianchi,M.E.Release of chromatin protein HMGB1 by necrotic cells triggers inflammation.Nature,2002,418(6894):191-195
75.Tsung,A.,Sahai,R.,Tanaka,H.,Nakao,A.,Fink,M.P.,Lotze,M.T.,Yang,H.,Li,J.,Tracey,K.J.,Geller,D.A.,Billiar,T.R.The nuclear factor HMGB1 mediates hepatic injury after murine liver ischemia-reperfusion.J Exp Meal,2005,201(7):1135-1143
76.Erlandsson Harris,H.,Andersson,U.Mini-review:The nuclear protein HMGB1as a proinflammatory mediator.Eur J Immunol,2004,34(6):1503-1512
77.Harris,H.E.,Raucci,A.Alarmin(g)news about danger:workshop on innate danger signals and HMGB1.EMBO Rep,2006,7(8):774-778
78.Mantell,L.L.,Parrish,W.R.,Ulloa,L.Hmgb-1 as a therapeutic target for infectious and inflammatory disorders.Shock,2006,25(1):4-11
79.Parrish,W.,Ulloa,L.High-mobility group box-1 isoforms as potential therapeutic targets in sepsis.Methods Mol Biol,2007,361 145-162
80.Yamada,S.,Maruyama,I.HMGB1,a novel inflammatory cytokine.Clin Chim Acta,2007,375(1-2):36-42
81.Yang,H.,Wang,H.,Czura,C.J.,Tracey,K.J.The cytokine activity of HMGB1.J Leukoc Biol,2005,78(1):1-8
82.Hunter,P.Sepsis under siege:a new understanding of sepsis might lead to the development of therapies to treat septic shock.EMBO Rep,2006,7(7):667-669
83.Hamik,A.,Lin,Z.,Kumar,A.,Balcells,M.,Sinha,S.,Katz,J.,Feinberg,M.W.,Gerzsten,R.E.,Edelman,E.R.,Jain,M.K.Kruppel-like factor 4 regulates endothelial inflammation.J Biol Chem,2007,282(18):13769-13779
[1]Dynan WS,Tjian R.The promoter-specific transcription factor Sp1 binds to upstream sequences in the SV40 early promoter.Cell,35:79-87.
[2]Kadonaga JT,Carner KR,Masiarz FR,et al.Isolation of cDNA encoding transcription factor Sp1 and functional analysis of the DNA binding domain.Cell,51:1079-1090.
[3]Turner J,Crossley M.Mammalian Kruppel-like transcription factors:more than just a pretty finger.Trends Biochem Sci,24:236-240.
[4]Black AR,Black JD,Azizkhan-Clifford J.Sp1 and kruppel-like factor family of transcription factors in cell growth regulation and cancer.J Cell Physiol,188:143-160.
[5]Dang DT,Pevsner J,Yang VW.The biology of the mammalian Kruppel-like family of transcription factors.Int J Biochem Cell Biol,32:1103-1121.
[6]Bieker JJ.Kruppel-like factors:three fingers in many pies.J Biol Chem,276:34355-34358.
[7]Cook T,Gebelein B,Urrutia R.Spl and its likes:biochemical and functional predictions for a growing family of zinc finger transcription factors.Ann NY Acad Sci,880:94-102.
[8]Philipsen S,Suske G.A tale of three fingers:the family of mammalian Sp/XKLF transcription factors.Nucleic Acids Res,27:2991-3000.
[9]Suske G.The Sp-family of transcription factors.Gene,238:291-300.
[10]Oates AC,Pratt SJ,Vail B,et al.The zebrafish klf gene family.Blood,2001,98:1792-1801.
[11]Patel NH,Prince V.Beyond the Hox complex.Genome Biol,1:reviews 1027.1-1027.4.
[12]Ferrier DE,Holland PW.Ancient origin of the Hox gene cluster.Nat Rev Genet,2:33-38.
[13]Eichler EE,Hoffman SM,Adamson AA,et al.Complex beta-satellite repeat structures and the expansion of the zinc finger gene cluster in 19p12.Genome Res,8:791-808.
[14]Song C-Z,Keller K,Murata K.et al.Functional interaction between coactivators CBP/p300,PCAF,and transcription factor FKLF2.J Biol Chem,277:7029-7036.
[15]Zhang W,Kadam S,Emerson BM,et al.Site-specific acetylation by p300 or CREB binding protein regulates erythroid Kruppel-like factor transcriptional activity via its interaction with the SWI-SNF complex.Mol Cell Biol,21:2413-2422.
[16]Shields JM,Yang VW.Two potent nuclear localization signals in the gut-enriched Kruppel-like factor define a subfamily of closely related Kruppel proteins.J Biol Chem,272:18504-18507.
[17]Song A,Patel A,Thamatrakoln K,et al.Functional domains and DNA-binding sequences of RFLAT-1/KLF13,a Kruppel-like transcription factor of activated T lymphocytes.J Biol Chem,277:30055-30065.
[18]Wolfe SA,Neldudova L,Pabo CO.DNA recognition by Cys2His2 zinc finger proteins.Aunu Rev Biophys Biomol Struct,29:183-212.
[19]Elrod-Erickson M,Rould MA,Neldudova L,et al.Zif268 protein-DNA complex refined at 1.6 A:a model system for understanding zinc finger-DNA interactions.Structure,4:1171-1180.
[20]Kim CA,Berg JM.A resolution crystal structtLre of a designed zinc finger protein bound to DNA.Nat Struct Biol,3:940-945.
[21]Narayan VA,Kriwacki RW,Caradonna JP.Structures of zinc finger domains from transcription factor Sp1.Insights into sequence-specific protein-DNA recognition.J Biol Chem,272:7801-7809.
[22]Cook T,Gebelein B,Mesa K,et al.Molecular cloning and characterization of TIEG2 reveals a new subfamily of transforming growth factor-beta-inducible Sp1-like zinc finger-encoding genes involved in the regulation of cell growth.J Biol Chem,273:25929-25936.
[23]Kaczynski J,Zhang J-S,Ellenfieder V,et al.The Spl-like protein BTEB3inhibits transcription via the BTE box by interacting with mSin3A and HDAC-1co-repressors and competing with Sp1.J Biol Chem,276:36749-36756.
[24]Sogawa K,Kikuchi Y,Imataka H,et al.Comparison of DNA binding properties between BTEB1 and Sp1.J Biochem,114:605-609.
[25]Hagen G,Muller S,Beato M,et al.Cloning by recognition site screening of two novel GT box binding proteins:a family of Sp1 related genes.Nucleic Acids Res,20:5519-5525.
[26]Kingsley C,Winoto A.Cloning of GT box-binding proteins:a novel Sp1multigene family regulating T-cell receptor gene expression.Mol Cell Biol,12:4251-4261.
[27]Ryu S,Zhou S,Ladurner AG,et al.The transcriptional cofactor complex CRSP is required for activity of the enhancerbinding protein Sp1.Nature,397:446-450.
[28]Cook T,Gebelein B,Belal M,et al.Three conserved transcriptional repressor domains are a defining feature of the TIEG subfamily of Sp1-like zinc finger proteins.J Biol Chem,274:29500-29504.
[29]Zhang JS,Moncrieffe MC,Kaczynski J,et al.A conserved alpha-helieal motif mediates the interaction of Sp1-like transcriptional repressors with the corepressor mSin3A.Mol Cell Biol,21:5041-5049.
[30]Gill G,Pascal E,Tseng ZH,et al.A glutamine-rich hydrophobic patch in transcription factor Sp1 contacts the dTAFⅡ110 component of the Drosophila TFⅡD complex and mediates transcriptional activation.Proc Natl Acad Sci,91:192-196.
[31]Van Vliet J,Turner J,Crossley M.Human Kruppel-like factor 8:a CACCC-box binding protein that associates with CtBP and represses transcription.Nucleic Acids Res,28:1955-1962.
[32]Ellenrieder V,Zhang J-S,Kaczynski J,et al.Signaling disrupts mSin3A binding to the Mad1-like Sin3-interacting domain of TIEG2,an Sp1-like repressor.EMBO J,21:2451-2460.
[33]Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest.J Biol Chem,1996,271:20009-20017.
[34]Yet SF,McA'Nulty MM,Folta SC,et al.Human EZF,a Kruppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem,273:1026-1031.
[35]Basu P,Morris PE,Haar JL,et al.KLF2 is essential for primitive erythropoiesis and regulates the human and murine embryonic beta-like globin genes in vivo. Blood,106(7):2566-2571.
[36]Katz JP,Perreault N,Goldstein BG,et al.The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon.Development,2002,129(11):2619-2628.
[37]Whitney EM,Ghaleb AM,Chen X,et al.Transcriptional profiling of the cell cycle checkpoint gene kruppel-like factor 4 reveals a global inhibitory function in macromolecular biosynthesis.Gene Expr,2006,13(2):85-96.
[38]Chen X,Whitney EM,Gao SY,et al.Transcriptional profiling of Kruppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.J Mol Biol,2003,326:665-677.
[39]Blanchon L,Nores R,Gallot D,et al.Activation of the human pregnancy-specific glycoprotein PSG-5 promoter by KLF4 and Sp1.Biochem Biophys Res Commun,2006,343(3):745-753.
[40]Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Kruppel-like factor (Kruppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275:18391-18398.
[41]Jenkins TD,Opitz OG,Okano J,et al.Transactivation of the human keratin 4and Epstein-Barr virus ED-L2 promoters by gut-enriched Kruppel-like factor.J Biol Chem,1998,273:10747-10754.
[42]Shie JL,Chen ZY,Fu M,et al.Gut-enriched Kruppel-like factor represses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28:2969-2976.
[43]Zhang W,Shields JM,Sogawa K,et al.The gut-enriched Kruppel-like factor suppresses the activity of the CYP1A1 promoter in an Sp1-dependent fashion.J Biol Chem,1998,273:17917-17925.
[44]Yoon HS,Yang VW.Requirement of Kruppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004,279:5035-5041.
[45]Yoon HS,Ghaleb AM,Nandan MO,et al.Kruppel-like factor 4 prevents centrosome amplification following gamma-irradiation-induced DNA damage.Oncogene,2005,24(25):4017-4025.
[46]Segre JA,Bauer C,Fuchs E.Klf4 is a transcription factor required for establishing the barrier function of the skin.Nat Genet,1999,22:356-360.
[47]Brembeck FH,Rustgi AK.The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1.J Biol Chem,2000,275:28230-28239.
[48]Katz JP,Perreault N,Goldstein BG,et al.Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach.Gastroenterology,2005,128(4):935-945.
[49]Piccinni SA,Bolcato-Bellemin AL,Klein A,et al.Kruppel-like factors regulate the Lamal gene encoding the laminin alphal chain.J Biol Chem,2004,279:9103-9114.
[50]Gardiner MR,Daggett DF,Zon LI,et al.Zebrafish KLF4 is essential for anterior mesendoderm/pre-polster differentiation and hatching.Dev Dyn,2005,234(4):992-996.
[51]Li Y,McClintick J,Zhong L,et al.Murine embryonic stem cell differentiation is promoted by SOCS-3 and inhibited by the zinc finger transcription factor Klf4.Blood,2005,105(2):635-637
[52]Chiefari E,Brunetti A,Arturi F,et al.Increased expression of AP2 and Sp1transcription factors in human thyroid tumours:a role in NIS expression regulation? BMC Cancer.2:35.
[53]Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Kruppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23:395-402.
[54]Wei D,Gong W,Kanai M,et al.Drastic down-regulation of Kruppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65:2746-2754.
[55]Foster KW,Ren S,Louro ID,et al.Oncogene expression cloning by retroviral transduction of adenovirus E1Aimmortalized rat kidney RK3E cells:transformation of a host with epithelial features by c-MYC and the zinc finger protein GKLF.Cell Growth Differ,1999,10:423-434.
[56]Suzuki T,Shen H,Akagi K,et al.New genes involved in cancer identified by retroviral tagging.Nature Genet,2002,32:166-174.
[57]Foster KW,Liu Z,Nail CD,et al.Induction of KLF4 in basal keratinocytes blocks the proliferation-differentiation switch and initiates squamous epithelial dysplasia.Oncogene,2005,24:1491-1500.
[58]Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000,60:6488-6495.
[59]Pandya AY,Talley LI,Frost AR,et al.Nuclear localization of KLF4 is associated with an aggressive phenotype in early-stage breast cancer.Clin Cancer Res,2004,10:2709-2719.
[60]Raman V,Martensen SA,Reisman D,et al.Compromised HOXA5 function can limit p53 expression in human breast tumors.Nature,2000,405:974-978.
[61]SenBanerjee S,Lin Z,Atkins GB,et al.KLF2 is a novel transcriptional regulator of endothelial proinflammatory activation.J Exp Med.199:1305-1315.
[62]McCormick SM,Eskin SG,McIntire LV,et al.DNA microarray reveals changes in gene expression of shear stressed human umbilical vein endothelial cells.Proc Nail Acad Sci.98:8955-8960.
[63]Adam PJ,Regan CP,Hautmann MB,et al.Positive- and negativeacting Kruppel-like transcription factors bind a transforming growth factor beta control element required for expression of the smooth muscle cell differentiation marker SM22alpha in vivo.J Biol Chem.275:37798-37806.
[64]Liu Y,Sinha S,McDonald OG,et al.Kruppel-like factor 4 abrogates myocardin-induced activation of smooth muscle gene expression.J Biol Chem,280(10):9719-9727.
[65]Ai W,Liu Y,Langlois M,et al.Kruppel-like factor 4(KLF4)represses histidine decarboxylase gene expression through an upstream Sp1 site and downstream gastrin responsive elementsJ Biol Chem,2004,279(10):8684-8693.
[66]Feinberg MW,Cao Z,Wara AK,et al.Kruppel-like factor 4 is a mediator of proinflammatory signaling in macrophages.J Biol Chem,280(46):38247-38258.
[1]Nathalie Carayol,Alison Campbell,lsabelle Vachier,et al.Modulation of Cadherin and Catenins Expression by Tumor Necrosis Factor-α and Dexamethasone in Human Bronchial Epithelial Cells.Am J Respir Cell Mol Biol,2002,26:341-347.
[2]Sadikot,E.Duco Jansen,Blackwell,et al.High-Dose Dexamethasone Accentuates Nuclear Factor-κB Activation in Endotoxin-Treated Mice.Am J Respir Crit Care Med,2002,164:873-878.
[3]Tremblay LN,Slutsky AS.Ventilator-induced injury:from barotrauma to biotrauma.Proc Assoc Am Physicians,1998,110:482-488.
[4]Yi ES,Remick DG,Lim Y,et al.The intratracheal administration of endotoxin:X.Dexamethasone downregulates neutrophil emigration and cytokine expression in vivo.Inflammation,1996,20:165-175.
[5]Pugin J,Dunn I,Jolliet P,et al.Activation of human macrophages by mechanical ventilation in vitro.Am J Physiol(Lung Cell Mol Physiol),1998,275:L1040-L1050.
[6]Avery B.Nathens,Richard Bitar,Christopher Davreux,et al.Pyrrolidine Dithiocarbamate Attenuates Endotoxin-induced Acute Lung Injury.Am J Respir Cell Mol Biol,1997,17:608-616.
[7]Pugin J,Verghese G,Widmer MC,et al.The alveolar space is the site of intense inflammatory and profibrotic reactions in the early phase of acute respiratory distress syndrome.Crit Care Med,1999,27(2):304-312.
[8]Christman JW,Sadikot RT,Blackwell TS.The role of nuclear factor-kappa B in pulmonary diseases.Chest,2000,117(5):1482-1487.
[9]Papanicolaou DA,Wilder RL,Manolagas SC,et al.The pathophysiologic roles of interleukin-6 in human disease.Ann Intern Med,1998,128(2):127-137.
[10]Ranieri VM,Suter PM,Tortorella C,et al.Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome:a randomized controlled trial.JAMA,1999,282(1):54-61.
[11]William Y.Park,Richard B.Goodman,Kenneth P.Steinberg,et al.Cytokine Balance in the Lungs of Patients with Acute Respiratory Distress Syndrome.Am J Respir Crit Care Med,2001,164(10):1896-1903.
[12]Jurgen,Grzegorz,Anthony,et al.Critical Roles for Interleukin-4 and Interleuldn-5 during Respiratory Syncytial Virus Infection in the Development of Airway Hyper-responsiveness after Airway Sensitization.Am J Respir Crit Care Med,2000,162(2):380-386.
[13]James F.Chmiel,Michael W.Konstan,Jeannee.Knesebeck,et al.IL-10Attenuates Excessive Inflammation in Chronic Pseudomonas Infection in Mice.Am J Respir Crit Care Meal,2002,160:2040-2047.
[14]Shanley,T.P.,H.Schmal,H.P.Friedl,et al.Regulatory effects of intrinsic IL-10 in IgG immune complex- induced lung injury.J Immunol,1995,154:3454-3460.
[15]Bolger AP,Sharma R,Von Haeling S,et al.Effect of interlukin-10 on the production of tumor necrosis factor-α by peripheral blood mononuclear cells from patients with chronic heart failure.Am J Cardiol,2002,90(4):384-389.
[16]Lo CJ,Fu M,Cryer HG.Interleukin l0 inhibits alveolar macrophage production of inflammatory mediators involved in adult respiratory distress syndrome.J Surg Res,1998,79(2):179-184.
[17]Li Qi,Qian Guisheng,Zhang Qing,et al.The change in IL-13 mRNA expression in rat lungs with acute pulmonary injury induced big lipopolysaccharide.Chin J Burns,2002,18(3):145-148.
[18]Ashwood P,Harvey R,Verjee T,et al.Functional interactions between mucosal IL-1,IL-ra and TGF-beta 1 in ulcerative colitis.Inflamm Res,2004,53:53-59.
[19]Mitsuyama K,Tomiyasu N,Suzuki A,et al.A form of circulating interleukin-6receptor component soluble gp130 as a potential interleukin-6 inhibitor in inflammatory bowel disease.Clin Exp Immunol,2006,143(1):125-131.
[20]Monteleone G,Parrello T,Luzza F,et al.Response of human intestinal lamina additive effects of interleukin 15 and 7.Gut,1998,43:620.
[21]Furuya D,Yagihashi A,Komsysu M,et al.Serum interleukin-18 concentrations in patients with inflammatory bowel disease.J Immunother,2002,(suppl):565.
[22]Aizawa Y,Sutoh S,Matsuoka M,et al.Association of interleukin-18 gene single-nucleotidepolymorphisms with susceptibility to inflammatory bowel disease.Tissue Antigens,2005,65:88-92.
[23]Lindsay JO,Ciesielski CJ,Scheinin T,et al.Local delivery of adenoviral vectors encodingmurine interleukin 10 induces colonic interleukin 10production and is therapeutic for murine colitis.Gut,2003,52:981-987.
[24]Melgar S,YeungMM,Bas A,et al.Overexpression of interleukin 10 in mucosal T cells of patients with active ulcerative colitis.Clin Exp Immunol,2003,134:127-137.
[25]Kadivar K,Ruchelli ED,Markowitz JE,et al.Intestinal interleukin-13 in pediatric inflammatory bowel disease patients.Inflamm Bowel Dis,2004,10(5):593-598.
[26]Fuss IJ,Heller F,Boirivant M,et al.Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis.J Clin Invest,2004,113:1490-1497.
[27]蒋明,DAVID YU,林孝义,等.中华风湿病学.北京:华夏出版社,2004:771-824.
[28]Dayer JM.The pivotal role of interleukin in the clinical manifestations of rheumatoid arthritis.Rheumatology,2003,42(suppl 2):3-10.
[29]Lee DM,Weinblatt ME.Rheumatoid Arthritis.Lancet,2001,358(9258):903-911.
[30]Abramson SB,Amin A.Blocking the effects of IL-1 in rheumatoid arthritis protects bone and cartilage.Rheumatology,2002,41(9):972-980.
[31]Tanaka M,Harigai M,Kawaguchi Y,et al.Mature form of interleukin 18 is expressed in rheumatoid arthritis synovial tissue and contributes to interferon-γproduction by synovial cells.J Rheumatol,2001,28(8):1779-1787.
[32]Yamamura M,Kawashima M,Taniai M,et al.Interferon-γ-inducing activity of interleukin-18 in the joint with rheumatoid arthritis.Arthritis Rheum,2001,44(2):275-285.
[33]Olee T,Hashimoto S,Quach J,et al.IL-18 is produced by articular chondrocytes and induces proinflammatory and catabolic responses.J Immunol,1999,162(2):1096-1100.
[34]Mcinnesi B,Al-Mughales J,FIELD M,et al.The role of interleukin-15 in T cell migration and activation in rheumatoid arthritis.Nat Med,1996,2(2):175-182.
[35]Ziolkowsk AM,Ko CA,Luszczykiewicz G,et al.High levels of IL-17 in rheumatoid arthritis patients:IL-15 triggers in vitro IL-17 production via cyclosporin A-sensitive mechanism.J Immunol,2000,164(5):2832-2838.
[36]Kurowsk AM,Rudnick AW,Kontny E,et al.Fibroblast-like synoviocytes from rheumatoid arthritis patients express functional IL-15 receptor complex:endogenous IL-15 in autocrine fashion enhances cell proliferation and expression of Bcl-xl and Bcl-2.J Immunol,2002,169(4):1760-1767.
[37]Miyazawa K,Mori A,Yamamoto K,et al.Constitutive transcription of the human interleukin-6 gene by rheumatoid synvoiocytes.Spontaneous activation of N F-κB and CBF1.Am J Pathol,1998,152(3):793-803.
[38]Atsumi T,Ishihara K,Kamimura D,et al.A point mutation of Tyr-759 in interleukin-6 family cytokine receptor subunit gp 130 causes autoimmune arthritis.J Exp Med,2002,196(7):979-990.
[39]Yashimoto T,Nagai N,Ohkusu K,et al.LPS-stimulated SJL macrophages produce IL-12 and IL-18 that inhabit IgE production in vitro by induction of IFN-gamma production from CD 3intIL-2R beta+ T cells.Immunol,1998,161(3):1483-1492.
[40]Lubberts E,Van denbersselaar L,Oppers-Walgreen B,et al.IL-17 promotes bone erosion in m urine collagen-induced arthritis through loss of the receptor activator of N F-Kb ligand / osteoprotegerin balance.J Immunol,2003,170(5):12655-12662.
[41]Chen XC,Xiao R.Investigation of ralve of rheumafoid factor and antikeratin antibody in diagnosing Rheumafoid arthritis.China Journal of Modem Medicine,2005,15(8):1265-1268.
[42]胡森,姚永明.脓毒症和全身炎症反应综合征.北京:科学出版社,1999.
[43]Nakamura T,Kawagoe Y,Suzuki T,et al.Changes in plasma interleukin-18 by direct hemoperfusion with polymyxin B-immobilized fiber in patients with septic shock.Blood Purif,2005,23(6):417-420.
[44]Oberholzer A,Steckholzer U,Kurimoto M,et al.Interleukin-18 plasma levels are increased in patients with sepsis compared to severely injured patients.Shock,2001,16(6):411-414.
[45]Netea MG,Kullberg BJ,Verschueren I,et al.Interleukin-18 induces production of proinflammatory cytokines in mice:no intermediate role for the cytokines of the tumor necrosis factor family and interleukin-1β.Eur J Immunol,2000,30(10):3057-3060.
[46]Puren,AJ,Fantuzzi G,Cu Y,et al.Interleukin-18(IFN-γ inducing factor)induces IL-8 and IL-1β via TNF-α production from non-CD14 + human blood mononuclear cells.J Clin Investig,1998,101(3):711-721.
[47]Hoshino T,Wiltrout RH,Young HA.IL-18 is a potent coinducer of IL-13 in NK and T cells:a new potential role for IL-18 inmodulating the immune response.J Immunol,1999,162(9):5070-5077.
[48]Yoshimoto T,Tsutsui H,Tominaga K,et al.IL-18,although antiallergic when administered with IL-12,stimulates IL-4 and histamine release by basophils.Proc N atl Acad Sci USA,1999,96(24):13962-13966.
[49]Armstrong L,MillarAB.Relative p roduction of tumour necrosis factor alpha and interlerkin - 10 in adult resp irationg distress syndrome.Thorax,1997,52:442 - 446.
[50]Lo CJ,FuM,CryerHC,et al.Interukin-10,inhabits celveolar macrohage production of inflammatory mediator involved in adult respiratory distress syndrome.Journal of Surgical Research,1998,72:179-184.
[51]Takakuwa T,Endo S,Shirakura Y,et al.Interleukin-10 gene transfer imp roves the survival rate of mice inoculated with Escherichia coli.Crit Care Med,2000,132:383-390.
[52]Patel RT,Deen KI,Youngs D,et al.Interleukin 6 is a prognostic indicator of outcome in severe intra-abdominal sepsis.Br J Surg,1994,81(9):1036-1038.
[53]Bone RC.Immunologic dissonance:a continuing evolution in our understanding of the systemic inflammatory response syndrome(SIRS)and the multiple organ dysfuncion syndrome(MODS).Ann Intern Med,1996,125(8):680-687.