COPD中组蛋白乙酰化致IL-8表达增高的机制及MAPK途径的调控作用
|
摘要
研究背景COPD是一种慢性气道炎症性疾病,以炎症基因表达增高为特点。香烟烟雾是COPD的主要致病因素,它可以导致氧化应激,激活转录因子,诱导炎症基因转录。香烟烟雾诱导的炎症反应在COPD的发生发展中起着关键的作用。组蛋白乙酰化/去乙酰化是影响基因转录的关键的调节器。组蛋白乙酰化和去乙酰化作用的失平衡会导致肺内促炎症反应基因的过度转录,形成慢性炎症循环,可能对COPD的发生发展产生重要影响。研究表明,氧化应激和细胞核心组蛋白乙酰化/去乙酰化失平衡有关,可诱导组蛋白乙酰化。氧化应激可能需要依赖于信号转导途径的介导作用才能诱导组蛋白乙酰化。研究表明,氧化应激可以激活MAPK途径,MAPK途径的激活在气道炎症中起着重要作用。而且,在某些条件下,MAPK途径能够影响组蛋白结构,可使组蛋白发生磷酸化或乙酰化。因此,在COPD中,MAPK途径可能参与了组蛋白乙酰化的调控。本研究拟以COPD大鼠模型和正常人支气管上皮细胞为研究对象,探讨香烟烟雾诱导气道上皮组蛋白乙酰化的机制和其对IL-8表达影响以及MAPK途径在该过程中的调控作用。
第一章乙酰化组蛋白H4及HDAC2在COPD肺组织中的表达及氨茶碱的抗炎作用
目的观察乙酰化组蛋白H4和组蛋白去乙酰基酶2(HDAC2)在慢性阻塞性肺疾病(COPD)大鼠肺组织中的表达和它们对IL-8表达的影响,以及氨茶碱的干预作用,以期探讨COPD中组蛋白乙酰化状态及其对炎症因子IL-8表达的影响,同时说明氨茶碱的抗炎作用。
方法36只Wistar大鼠随机均分为3组:正常对照组、COPD模型组和氨茶碱干预组。采用被动吸烟加气管内注射脂多糖法建立大鼠COPD模型,干预组给予腹腔注射氨茶碱(5mg·kg~(-1)·d)。造模完成后,测定各组大鼠的肺功能、观察肺组织病理学变化;用比色法测定各组大鼠肺组织HDAC活性;免疫组织化学法及western blot法观察乙酰化组蛋白H4及HDAC2在肺组织中的表达情况;应用ELISA法检测支气管肺泡灌洗液中IL-8的水平;RT-PCR方法检测肺组织中IL-8mRNA及HDAC2mRNA水平。
结果与正常对照组比较,模型组动物的PEF、FEV_(0.3)、FEV_(0.3)/FVC均显著降低,氨茶碱干预能改善肺功能。HDAC活性在模型组最低,显著低于对照组,氨茶碱可使HDAC活性部分恢复。免疫组化及western blot的结果显示,和对照组相比,乙酰化组蛋白H4在模型组的表达明显增高;和模型组相比,氨茶碱干预后乙酰化组蛋白H4的表达显著降低;和对照组相比,HDAC2在模型组的表达降低,氨茶碱干预后其表达有所增高。与正常对照组相比,模型组大鼠支气管肺泡灌洗液中IL-8的浓度明显增高,大鼠肺组织中IL-8mRNA的水平也显著增高;和模型组比较,氨茶碱干预能够使支气管肺泡灌沈液中的IL-8表达和IL-8mRNA的水平均下降。而HDAC2mRNA水平在三组之间没有差异。
结论COPD大鼠模型中组蛋白乙酰化增强,导致炎症因子IL-8的高表达,氨茶碱能够通过激活组蛋白的去乙酰化而减少IL-8的表达,起到抗炎作用。
第二章香烟烟雾通过MAPK途径诱导气道上皮细胞组蛋白乙酰化上调IL-8的表达
目的观察香烟烟雾刺激正常人支气管上皮细胞后MAPK途径蛋白和HDAC2蛋白的表达,进一步研究MAPK途径(p38、ERK1/2和JNK)抑制剂对香烟烟雾刺激后人支气管上皮细胞中HDAC活性、乙酰化组蛋白H4以及IL-8表达的影响,以期探讨香烟烟雾刺激正常人支气管上皮细胞后诱导组蛋白乙酰化致IL-8表达增高的机制以及MAPK途径在该过程中的调控作用
方法培养正常人支气管上皮(NHBE)细胞,分别用5%和10%的香烟烟雾提取物(CSE)进行刺激,用免疫细胞化学和western blot的方法观察香烟烟雾刺激后MAPK途径蛋白的激活形式p-p38、p-ERK1/2和p-JNK以及HDAC2在NHBE中的表达。再分别用10%CSE、TSA(HDAC抑制剂)、氨茶碱+CSE、SB203580(p38抑制剂)+CSE、PD98059(ERK抑制剂)+CSE以及SP600125(JNK抑制剂)+CSE对支气管上皮细胞进行干预,用比色法检测HDAC活性,用免疫细胞化学和western blot的方法观察乙酰化组蛋白H4表达的变化,用RT-PCR和ELISA方法进一步观察不同刺激对IL-8mRNA和细胞培养上清液中IL-8表达的影响。
结果CSE刺激能够使MAPK途径激活,p-p38、p-ERK1/2和p-JNK蛋白的表达在CSE刺激组明显高于对照组,而HDAC2的表达则显著低于对照组。CSE刺激具有和TSA类似的效应,能够使NHBE中HDAC活性显著下降,乙酰化组蛋白H4表达显著增高,伴随细胞培养上清液中IL-8表达的增高和细胞中IL-8mRNA水平的增加;氨茶碱干预能够激活HDAC活性,减少乙酰化组蛋白H4表达和IL-8表达;SB203580和PD98059能够下调CSE刺激诱导的乙酰化组蛋白H4的表达和随后的IL-8基因的表达,而SP600125干预对香烟烟雾诱导NHBE组蛋白乙酰化的过程不起作用,也不能下调IL-8的表达。SB203580、PD98059和SP600125均对HDAC活性没有影响。
结论体外CSE刺激NHBE可诱导组蛋白乙酰化,上调IL-8基因表达;氨茶碱能够激活HDAC活性减少组蛋白乙酰化而发挥抗炎作用;MAPK途径中的p38和ERK1/2能下调CSE诱导的组蛋白乙酰化和IL-8基因转录。
Background:Chronic obstructive pulmonary disease(COPD) is a chronic inflammatory disease of airway,characterized by excessive inflammatory gene expression.Cigarette smoke is the main etiological factor in the pathogenesis of COPD.It can cause oxidative stress,activate transcription factors nuclear factor and enhance proinflammatory gene transcription.Cigarette smoke-triggered inflammation is considered to play a central role in the development of COPD.Histone acetylation and deacetylation is a key regulator of the specificity and duration of gene transcription.Disruption in the nuclear histone acetylation/deacetylation balance may result in excessive transcription of specific proinflammatory genes in the lungs,finally,chronic inflammatory cycle will develop,and it may have great influence on COPD.It was indicated that oxidative stress has direct relationship with the disruption of histone acetylation/ deacetylation balance and it can enhance the acetylation of histone protein.Oxidative stress has been suggested to influence histone acetylation depending on some signal transduction pathway.It has been reported that oxidative stress can activate MAPK(Mitogen-activated protein kinases) pathway,which play an important role in the inflammation of airway.Furthermore,MAPK pathway can influence the structure of histone,it maybe induce histone phosphorylation or acetylation in some condition.SO,MAPK pathway may participate in the regulation of histone acetylation in COPD.Based on these results,we explored the histone acetylation regulating IL-8 release mediated by cigarette smoke and the regulative effect of MAPK pathway in COPD rat and bronchial epithelail cell.
Chapter One Expression of acetylated histone H4 and HDAC2 in the lung tissues of COPD rat and the anti-inflammatory effect of Aminophylline
Objective:To study the expression of acetylated histone H4 and histone deacetylase(HDAC2) in the lung tissues of COPD rat model and its influence on IL-8 expression.At the same time,to explore the anti-inflammatory effect of Aminophylline.
Methods:36 Wister rats were divided into three groups at random:control group、COPD group and Aminophylline group.Rat COPD model was established by intratracheal instillation of lipopolysaccharide(LPS) twice and exposure to cigarette smoke daily. Aminophylline group received Aminophylline(5 mg·kg~(-1)·d ) daily via the abdominal cavity injection.The spirometry was conducted and the pathological changes were observed after the model was established.HDAC activity was examined by colorimetric method.The expression of protein of acetylated H4 and HDAC2 in the lung tissues was examined by using immunohistochemistry and western blot.The concentrations of IL-8 in bronchoalveolar lavage fluid(BALF) was measured by enzyme-linked inmunosorbent assay(ELISA).And the mRNA of IL-8 and HDAC2 in the lung tissues was detected by reverse transcription-polymerase chain reaction(RT-PCR) respectively.
Results:Significant decrease of PEF、FEV0.3、FEV_(0.3)/FVC were found in the COPD rat model group compared with the control group. Aminophylline could improve lung function.The activity of HDAC was lower in the COPD group than in the control group,and Aminophylline could restore HDAC activity partly.In the COPD group,the expression of acetylated H4 protein was increased markedly compared with the control group,and Aminophylline could decrease acetylated H4 protein.The expression of HDAC2 protein was decreased in the COPD group and Aminophylline could enhance the expression of HDAC2 protein.The expression of IL-8 mRNA and the concentrations of IL-8 in BALF were higher in the COPD group than in the control group.Aminophylline could decrease IL-8 levels,and this was associated with increased HDAC activity and HDAC2 protein levels.But there was no difference in HDAC2 mRNA levels between these three groups.
Conclusion:In COPD,histones were highly acetylated in the lung tissue.The acetylation of histones can induce increased expression of IL-8.While,Aminophylline can activate HDAC and decrease acetylation of histones as well as the expression of IL-8,So it has the effect of anti-inflammation.
Chapter Two Cigarette smoke induces histone acetylation and up-regulates IL-8 expression in NHBE cells via MAPK pathway
Objective:To investigate the mechanism of histone acetylation mediated by cigarette smoke inducing bronchial epithelial IL-8 release and the regulative effect of MAPK pathway in this process.
Methods:We treated normal human bronchial epithelial(NHBE)cells with 5%and 10%cigarette smoke extract (CSE)respectivly,then the expression of p-p38、p-ERK1/2、p-JNK(activated MAPK pathway protein)and HDAC2 in NHBE cells were detected by immunocytochemistry and western blot.After that,we treated NHBE cells with 10%CSE、TSA(HDAC inhibitor)、Aminophylline+CSE、SB203580(p38 inhibitor)+CSE、PD98059 (ERKinhibitor)+CSE and SP600125(JNK inhibitor)+CSE respectively. HDAC activity was examined by colorimetric method.The expression of protein of acetylated H4 in NHBE cells was examined by using immunocytochemistry and western blot.The concentrations of IL-8 in NHBE cells supernatant was measured by enzyme-linked inmunosorbent assay(ELISA).And the level of IL-8mRNA in NHBE cells was detected by reverse transcription-polymerase chain reaction(RT-PCR) respectively.
Results:CSE stimulation could activate MAPK pathway.In the presence of CSE,the expression of p-p38、p-ERK1/2 and p-JNK significantly increased.While,the the expression of HDAC2 decreased in the CSE group.In the CSE and TSA group,the activity of HDAC was lower than in the control group,but the expression of acetylated H4 protein was increased markedly compared with the control group,and the concentrations of IL-8 in supernatant and the expression of IL-8 mRNA were higher than in the control group.Aminophylline could restore HDAC activity partly,as a result,decreasing the expression of acetylated H4 and IL-8.The expression of acetylated H4 and IL-8 which were induced by CSE was inhibited by SB203580 and PD98059,but not by SP600125.SB203580、PD98059 and SP600125 had no effect on HDAC activity.
Conclusion:In NHBE cells,CSE stimulation could induce histone acetylation associated with IL-8 expression subsequently.Aminophylline may fulfill the effect of anti-inflammation through activating HDAC and decreasing acetylation of histone.p38 and ERK1/2 MAPK pathway could down-regulate histone acetylation and inhibit the expression of IL-8 subsequently which were induced by CSE.
第一章乙酰化组蛋白H4及HDAC2在COPD肺组织中的表达及氨茶碱的抗炎作用
目的观察乙酰化组蛋白H4和组蛋白去乙酰基酶2(HDAC2)在慢性阻塞性肺疾病(COPD)大鼠肺组织中的表达和它们对IL-8表达的影响,以及氨茶碱的干预作用,以期探讨COPD中组蛋白乙酰化状态及其对炎症因子IL-8表达的影响,同时说明氨茶碱的抗炎作用。
方法36只Wistar大鼠随机均分为3组:正常对照组、COPD模型组和氨茶碱干预组。采用被动吸烟加气管内注射脂多糖法建立大鼠COPD模型,干预组给予腹腔注射氨茶碱(5mg·kg~(-1)·d)。造模完成后,测定各组大鼠的肺功能、观察肺组织病理学变化;用比色法测定各组大鼠肺组织HDAC活性;免疫组织化学法及western blot法观察乙酰化组蛋白H4及HDAC2在肺组织中的表达情况;应用ELISA法检测支气管肺泡灌洗液中IL-8的水平;RT-PCR方法检测肺组织中IL-8mRNA及HDAC2mRNA水平。
结果与正常对照组比较,模型组动物的PEF、FEV_(0.3)、FEV_(0.3)/FVC均显著降低,氨茶碱干预能改善肺功能。HDAC活性在模型组最低,显著低于对照组,氨茶碱可使HDAC活性部分恢复。免疫组化及western blot的结果显示,和对照组相比,乙酰化组蛋白H4在模型组的表达明显增高;和模型组相比,氨茶碱干预后乙酰化组蛋白H4的表达显著降低;和对照组相比,HDAC2在模型组的表达降低,氨茶碱干预后其表达有所增高。与正常对照组相比,模型组大鼠支气管肺泡灌洗液中IL-8的浓度明显增高,大鼠肺组织中IL-8mRNA的水平也显著增高;和模型组比较,氨茶碱干预能够使支气管肺泡灌沈液中的IL-8表达和IL-8mRNA的水平均下降。而HDAC2mRNA水平在三组之间没有差异。
结论COPD大鼠模型中组蛋白乙酰化增强,导致炎症因子IL-8的高表达,氨茶碱能够通过激活组蛋白的去乙酰化而减少IL-8的表达,起到抗炎作用。
第二章香烟烟雾通过MAPK途径诱导气道上皮细胞组蛋白乙酰化上调IL-8的表达
目的观察香烟烟雾刺激正常人支气管上皮细胞后MAPK途径蛋白和HDAC2蛋白的表达,进一步研究MAPK途径(p38、ERK1/2和JNK)抑制剂对香烟烟雾刺激后人支气管上皮细胞中HDAC活性、乙酰化组蛋白H4以及IL-8表达的影响,以期探讨香烟烟雾刺激正常人支气管上皮细胞后诱导组蛋白乙酰化致IL-8表达增高的机制以及MAPK途径在该过程中的调控作用
方法培养正常人支气管上皮(NHBE)细胞,分别用5%和10%的香烟烟雾提取物(CSE)进行刺激,用免疫细胞化学和western blot的方法观察香烟烟雾刺激后MAPK途径蛋白的激活形式p-p38、p-ERK1/2和p-JNK以及HDAC2在NHBE中的表达。再分别用10%CSE、TSA(HDAC抑制剂)、氨茶碱+CSE、SB203580(p38抑制剂)+CSE、PD98059(ERK抑制剂)+CSE以及SP600125(JNK抑制剂)+CSE对支气管上皮细胞进行干预,用比色法检测HDAC活性,用免疫细胞化学和western blot的方法观察乙酰化组蛋白H4表达的变化,用RT-PCR和ELISA方法进一步观察不同刺激对IL-8mRNA和细胞培养上清液中IL-8表达的影响。
结果CSE刺激能够使MAPK途径激活,p-p38、p-ERK1/2和p-JNK蛋白的表达在CSE刺激组明显高于对照组,而HDAC2的表达则显著低于对照组。CSE刺激具有和TSA类似的效应,能够使NHBE中HDAC活性显著下降,乙酰化组蛋白H4表达显著增高,伴随细胞培养上清液中IL-8表达的增高和细胞中IL-8mRNA水平的增加;氨茶碱干预能够激活HDAC活性,减少乙酰化组蛋白H4表达和IL-8表达;SB203580和PD98059能够下调CSE刺激诱导的乙酰化组蛋白H4的表达和随后的IL-8基因的表达,而SP600125干预对香烟烟雾诱导NHBE组蛋白乙酰化的过程不起作用,也不能下调IL-8的表达。SB203580、PD98059和SP600125均对HDAC活性没有影响。
结论体外CSE刺激NHBE可诱导组蛋白乙酰化,上调IL-8基因表达;氨茶碱能够激活HDAC活性减少组蛋白乙酰化而发挥抗炎作用;MAPK途径中的p38和ERK1/2能下调CSE诱导的组蛋白乙酰化和IL-8基因转录。
Background:Chronic obstructive pulmonary disease(COPD) is a chronic inflammatory disease of airway,characterized by excessive inflammatory gene expression.Cigarette smoke is the main etiological factor in the pathogenesis of COPD.It can cause oxidative stress,activate transcription factors nuclear factor and enhance proinflammatory gene transcription.Cigarette smoke-triggered inflammation is considered to play a central role in the development of COPD.Histone acetylation and deacetylation is a key regulator of the specificity and duration of gene transcription.Disruption in the nuclear histone acetylation/deacetylation balance may result in excessive transcription of specific proinflammatory genes in the lungs,finally,chronic inflammatory cycle will develop,and it may have great influence on COPD.It was indicated that oxidative stress has direct relationship with the disruption of histone acetylation/ deacetylation balance and it can enhance the acetylation of histone protein.Oxidative stress has been suggested to influence histone acetylation depending on some signal transduction pathway.It has been reported that oxidative stress can activate MAPK(Mitogen-activated protein kinases) pathway,which play an important role in the inflammation of airway.Furthermore,MAPK pathway can influence the structure of histone,it maybe induce histone phosphorylation or acetylation in some condition.SO,MAPK pathway may participate in the regulation of histone acetylation in COPD.Based on these results,we explored the histone acetylation regulating IL-8 release mediated by cigarette smoke and the regulative effect of MAPK pathway in COPD rat and bronchial epithelail cell.
Chapter One Expression of acetylated histone H4 and HDAC2 in the lung tissues of COPD rat and the anti-inflammatory effect of Aminophylline
Objective:To study the expression of acetylated histone H4 and histone deacetylase(HDAC2) in the lung tissues of COPD rat model and its influence on IL-8 expression.At the same time,to explore the anti-inflammatory effect of Aminophylline.
Methods:36 Wister rats were divided into three groups at random:control group、COPD group and Aminophylline group.Rat COPD model was established by intratracheal instillation of lipopolysaccharide(LPS) twice and exposure to cigarette smoke daily. Aminophylline group received Aminophylline(5 mg·kg~(-1)·d ) daily via the abdominal cavity injection.The spirometry was conducted and the pathological changes were observed after the model was established.HDAC activity was examined by colorimetric method.The expression of protein of acetylated H4 and HDAC2 in the lung tissues was examined by using immunohistochemistry and western blot.The concentrations of IL-8 in bronchoalveolar lavage fluid(BALF) was measured by enzyme-linked inmunosorbent assay(ELISA).And the mRNA of IL-8 and HDAC2 in the lung tissues was detected by reverse transcription-polymerase chain reaction(RT-PCR) respectively.
Results:Significant decrease of PEF、FEV0.3、FEV_(0.3)/FVC were found in the COPD rat model group compared with the control group. Aminophylline could improve lung function.The activity of HDAC was lower in the COPD group than in the control group,and Aminophylline could restore HDAC activity partly.In the COPD group,the expression of acetylated H4 protein was increased markedly compared with the control group,and Aminophylline could decrease acetylated H4 protein.The expression of HDAC2 protein was decreased in the COPD group and Aminophylline could enhance the expression of HDAC2 protein.The expression of IL-8 mRNA and the concentrations of IL-8 in BALF were higher in the COPD group than in the control group.Aminophylline could decrease IL-8 levels,and this was associated with increased HDAC activity and HDAC2 protein levels.But there was no difference in HDAC2 mRNA levels between these three groups.
Conclusion:In COPD,histones were highly acetylated in the lung tissue.The acetylation of histones can induce increased expression of IL-8.While,Aminophylline can activate HDAC and decrease acetylation of histones as well as the expression of IL-8,So it has the effect of anti-inflammation.
Chapter Two Cigarette smoke induces histone acetylation and up-regulates IL-8 expression in NHBE cells via MAPK pathway
Objective:To investigate the mechanism of histone acetylation mediated by cigarette smoke inducing bronchial epithelial IL-8 release and the regulative effect of MAPK pathway in this process.
Methods:We treated normal human bronchial epithelial(NHBE)cells with 5%and 10%cigarette smoke extract (CSE)respectivly,then the expression of p-p38、p-ERK1/2、p-JNK(activated MAPK pathway protein)and HDAC2 in NHBE cells were detected by immunocytochemistry and western blot.After that,we treated NHBE cells with 10%CSE、TSA(HDAC inhibitor)、Aminophylline+CSE、SB203580(p38 inhibitor)+CSE、PD98059 (ERKinhibitor)+CSE and SP600125(JNK inhibitor)+CSE respectively. HDAC activity was examined by colorimetric method.The expression of protein of acetylated H4 in NHBE cells was examined by using immunocytochemistry and western blot.The concentrations of IL-8 in NHBE cells supernatant was measured by enzyme-linked inmunosorbent assay(ELISA).And the level of IL-8mRNA in NHBE cells was detected by reverse transcription-polymerase chain reaction(RT-PCR) respectively.
Results:CSE stimulation could activate MAPK pathway.In the presence of CSE,the expression of p-p38、p-ERK1/2 and p-JNK significantly increased.While,the the expression of HDAC2 decreased in the CSE group.In the CSE and TSA group,the activity of HDAC was lower than in the control group,but the expression of acetylated H4 protein was increased markedly compared with the control group,and the concentrations of IL-8 in supernatant and the expression of IL-8 mRNA were higher than in the control group.Aminophylline could restore HDAC activity partly,as a result,decreasing the expression of acetylated H4 and IL-8.The expression of acetylated H4 and IL-8 which were induced by CSE was inhibited by SB203580 and PD98059,but not by SP600125.SB203580、PD98059 and SP600125 had no effect on HDAC activity.
Conclusion:In NHBE cells,CSE stimulation could induce histone acetylation associated with IL-8 expression subsequently.Aminophylline may fulfill the effect of anti-inflammation through activating HDAC and decreasing acetylation of histone.p38 and ERK1/2 MAPK pathway could down-regulate histone acetylation and inhibit the expression of IL-8 subsequently which were induced by CSE.
引文
[1] Wu C. Chromatin remodeling and the control of gene expression. J Biol Chem,1997,272:28171-28174
[2] Sternglanz R. Histone acetylation: a gateway to transcriptional activation.Trends Biol Sci,1996,21 :357-358
[3] Urnov FD, Wolffe AP. Chromatin remodeling and transcriptional activation: the cast (in order of appearance). Oncogene,2001,20:2991-3006
[4] Walia H, Chen H,Sun JM,et al. Histone acetylation is required to maintain the unfolded nucleosome structure associated with transcribing DNA. J Biol Chem,1998,273,14516-14522
[5] Sambucetti LC, Fischer DD, Zabludoff S,et al. Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem, 1999,274:34940-34947
[6] Grunstein, M. Histone acetylation in chromatin structure and transcription.Nature, 1997,389:349-352
[7] Rahman I, Gilmour PS, Jimenez LA, MacNee W. Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation. Mol Cell Biochem,2002,234-235(1-2):239-248
[8] Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol,2004,31(6):633-642
[9] MacNee W.Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol,2001,429(1-3): 195-207
[10] Tikoo K, Lau SS,Monks TJ. Histone H3 phosphorylation is coupled to poly-(ADP-ribosylation)during reactive oxygen species-induces cell death in renal proximal tubular epithelial cells. Mol Pharmacol,2001, 60:394-402
[11] Thomson S, Mahadevan LC, Clayton AL. MAP kinase-mediated signalling to nucleosomes and immediate-early gene induction.Semin Cell Dev Bio,1999,10:205-214
[12]Saccani SS,Pantano,G Natoli.p38-Dependent marking of inflammatory genes for increased NF-κB recruitment.Nat Immunol,2002,3:69-75
[13]Miyata Y,Towatari M,Maeda T,et al.Histone acetylation induces by granulocyte colony stimulating factor in a MAP kinase-dependent manner.Biochemical and Biophysical Research Communications,2001,283:655-660
[14]Barnes PJ.Yheophylline:new perspectives for an old drug.Am J Respir Crit Care Med,2003,167:813-818
[15]Culpitt SV,de Matos C,Russell RE,et al.Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2002,165:1371-137
[16]Kobayashi M,Nasuhara Y,Betsuyaku T,et al.Effect of low dose theophylline on airway inflammation in COPD.Respirology,2004,9:249-254
[17]Cosio BG,Tsaprouni L,Ito K.Theophylline restores historic deacetylase activity and steroid responses in COPD macrophages.J Exp Med,2004,200:689-695
[18]Ito K,Lim S,Caramori G,et al.A molecular mechanism of action of theophylline:induction of histone deacetylase activity to decrease inflammatory gene expression.Proc Natl Acad Sci,2002,99:8921-8926
[19]Eberharter A,Becker PB.Histone acetylation:a switch between repressive and permissive chromatin:Second in review series on chromatin dynamics.EMBO Rep,2002,3:224-229
[20]Grunstein M.Histone acetylation in chromatin structure and transcription.Nature,1997,389(6649):349-352
[21]Hoffmann E,Dittrich-Breiholz O,Holtmann H,Kracht M.Multiple control of interleukin-8 gene expression.J Leukoc Biol,2002,72:847-855
[22]周青,贺菊乔,刘丽芳,等.紫金胶囊对细菌性前列腺炎模型大鼠炎性因子TNF-α及IL-8的作用.中国中西医结合外科杂志,2005,(11):56-58
[23]陈红梅,罗百灵,屈满英,等.红霉素对慢性阻塞性肺疾病大鼠基质金属蛋白酶-9的影响.中华结核和呼吸杂志,2008,31(9):702-703
[24]宋一平,崔德健,茅培英,等.慢性阻塞性肺疾病大鼠模型气道重塑及生长因子的研究.中华结核和呼吸杂志,2001,24:283-287
[25]邢传平,刘斌,董亮.免疫组织化学标记结果的判断方法.中华病理学杂志,2001,30(4):318
[26]Marwick JA,Kirkham PA,Stevenson CS,et al.Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs.American Journal of Respiratory Cell and Molecular Biology.2004,31:633-642
[27]Pauwels RA,B Soina,PMA Claverley,et al.Global strategy for the diagnosis,management,and prevention of chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2001,163:1256-1276.
[28]Rahman I,MacNee W.Lung glutathione and oxidative stress:implications in cigarette smoke-induced airways disease.Am J Physiol,1999,227,L 1067-L 1088
[29]Rahman I,MacNee W.Oxidative stress and regulation of glutathione synthesis in lung inflammation.Eur Respir J,2000,16:534-554
[30]Rahman I,MacNee W.The role of transcription factors in inflammatory lung diseases.Thorax,1998,53:601-612
[31]Rahman I.Oxidative stress,chromatin remodelling and gene transcription in inflammation and chronic lung disease.J Biochem Mol Biol,2003,36:95-109
[32]Barnes P J,Karin M.Nuclear factor-κB:a pivotal transcription factor in chronic inflammatory diseases.New Engl J Med,1997,336:1066-1071
[33]Wright JG,Christman JW.The role of nuclear factor κB in the pathogenesis of pulmonary diseases:implications for therapy.Am J Respir Med,2003,2:211-219
[34]Rahman I,W MacNee.Lung glutathione and oxidative stress:implications in cigarette smoke-induced airways disease.Am J Physiol,1999,227:L1067-L1088
[35]Church T,VA Pryor.Free radical chemistry of cigarette smoke and its toxicological implications.Environ Health Perspect,1985,46:111-126
[36]Imhof A,Wolffe AP.Transcription:gene control by targeted histone acetylation.Curr Biol,1998,8:R422-R424
[37] De Ruijter AJ, Van Gennip AH, Caron HN,et al. Histone deacetylases (HDACs):characterization of classical HDAC family.Biochem J,2003,370: 737-749
[38] Johnson CA, Turner BM. Histone deacetylase: complex transducers of nuclear signals. Cell Develop Biol,1999,10: 179-188
[39] Ito K, Lim S, Caramori G,et al. Cigarette smokingreduces histone deacetylase 2 xpression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J,2001,15: 1110-1112
[40] Berghe WV, Bosscher KD, Boone E, Plaisance S, Haegeman G: The nuclear factor-kB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter.J Biol Chem, 1999,274: 32091-32098
[41] Fusunyan RD, Quinn JJ, Fujimoto M, et al. Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.Mol Med, 1999,5: 631-640
[42] Pender SLF, Quinn JJ, Sanderson IR, MacDonald TT: Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells.Am J Physiol Gastrointest Liver Physiol,2000,279: G918-G924
[43] Y Elliott WM, Ito M. Total histone deacetylase activity decreases with increasing clinical stage of COPD. Am J Respir Crit Care Med,2004,169: 276
[44] Ito K, Ito M, Elliott WM, et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med,2005,352(19):1967-1976
[45] Ito K, Hanazawa T, Tomita K, et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun,2004,315(1):240-245
[46] Ischiropoulos H. Biological selectivity and functional aspects of protein tyrosine nitration. Biochem Biophys Res Commun,2003,305: 777-783
[47] Kramer OH, Zhu P, Ostendorff HP, et al. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J,2003,22:3411-3420
[48]Bames PJ,Pauwels RA.Theophylline in the management of asthma:time for reappraisal ? Eur Respir J,1994,7(3):579-591
[49]Rabe KF,Magnussen H,Dent G.Yheophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants.Eur Respir J,1995,8(4):637-642
[50]Markham A,Faulds D.Theophylline.A review of its potential steroid sparing effects in asthma.Drugs,1998,56(6):1081-1091
[51]Rabe KF,Dent G.Theophylline and airway inflammation.Clin Exp Allergy,1998,28(Suppl 3):35-41
[52]吕小琴,唐法娣.p38MAPK特异性抑制剂SB239063.国外医学呼吸系统分册,2004,24(1):38-39
[53]Chen K,Vita JA,Berk BC,et al.c-Jun N-terminal kinase activation by hydrogen peroxide in endothelial cells involves SRC-dependent epidermal growth factor receptor transactivation.J Biol Chem,2001,276(19):16045-16050
[54]Zhuang S,Schnellmann RG.H_2O_2-induced transactivation of EGF receptor requires Src and mediates ERK1/2,but not Akt,activation in renal cells.Am J Physiol Renal Physiol,2004,286(5):F858-F865
[55]Whitmarsh AJ,RJ Davis.Regulation of transcription factor function by phosphorylation.Cell Mol Life Sci,2000,57:1172-1183
[56]Janknecht R,Nordheim A.MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP.Biophys Res Commun,1996,228:831-837
[57]Baeza-Squiban A,Bonvallot V,Boland S,et al.Airborne particles evoke an inflammatory response in human airway epithelium.Activation of transcription factors.Cell Biol Toxicol,1999,15:375-380
[58]Hellermann GR,Nagy SB,Koong X,et al.Mechanisms of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells.Respir Res,2002,3:22-29
[59]屈满英,罗百灵,陈红梅,等.分泌型白细胞蛋白酶抑制剂对香烟烟雾提取物诱导人支气管上皮细胞炎症介质表达的影响.中华结核和呼吸杂志,2008,31(5):352-355
[60]Moodie FM,Marwick JA,Anderson CS,et al.Oxidative stress and cigarette smoke alter chromatin remodeling but differentially regulate NF-κB activation and proinflammatory cytokine release in alveolar epithelial cells.The FASEB Journal,2004,18(15):1897-1899
[61] Hortense Slevogt, Bernd Schmeck, Carola Jonatat,et al. Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-κB activation and histone deacetylase activity reduction. Am J Physiol Lung Cell Mol Physiol,2006,290: L818-L826
[62] Pryor WA, Stone K. Oxidants in cigarette smoke: radicals, hydrogen peroxides, peroxynitrate, and peroxynitrite. Ann NY Acad Sci, 1993,686:12-28
[63] Mio T, Romberger DJ , Thompson AB , et al . Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells. AmJ Respir Crit Care Med,1997,155:1770-1776
[64] Goodyear LJ,Chang PY,Sherwood DJ,et al. Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletalmuscle. Am J Physiol, 1996,271(2Pt1):E403-E408
[65] Mercer B, Kolesnikova N, Sonett J, D'Armiento J. Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke. J Biol Chem,2004,279(17):17690-17696
[66] Milligan SA, Owens MW, Grisham MB. Differential regulation of extracellular signal-regulated kinase and nuclear factor-kappa B signal transduction pathways by hydrogen peroxide and tumor necrosis factor. Arch Biochem Biophys,1998,352(2):255-262
[67] Jope RS, Zhang L, Song L. Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells. Arch Biochem Biophys,2000,376(2):365-370
[68] Lee K, Esselman WJ. Inhibition of PTPs by H2O2 regulates the activation of distinct MAPK pathways. Free Radic Biol Med,2002,33(8):1121-1132
[69] Tamura DY, Moore EE, Johnson JL,et al. p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary microvascular endothelial cells. Surgery, 1998,124(2):403-407,discussion 408
[70] Nick JA, Young SK, Brown KK, et al. Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation. J Immunol, 2000,164(4):2151-2159
[71] Underwood DC, Osborn RR, Bochnowicz S, et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol,2000,279(5):L895-L902
[72] Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene,2000,19(56):6550-6565
[73] Rhee SG, Chang TS, Bae YS, et al. Cellular regulation by hydrogen peroxide. J Am Soc Nephrol 2003,14(8 Suppl 3):S211-5.
[74] Kawasaki H, Schiltz L, Chiu R,et al. ATF-2 has instrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature,2000,405:195-200
[75] Adler V, Yin Z, Tew KD,Ronai, Z. Role of redox potential and reactive oxygen species in stress signaling. Oncogene,1999,18:6104-6111
[1] Rahman I, W MacNee. Lung glutathione and oxidative stress: implications in cigarette smoke-induced airways disease. Am J Physiol, 1999,227:L1067-L1088
[2] Church T VA Pryor. Free radical chemistry of cigarette smoke and its toxicological implications. Environ. Health Perspect, 1985,46:111-126
[3] Rahman I. Oxidative stress, chromatin remodelling and gene transcription in inflammation and chronic lung disease. J Biochem Mol Biol,2003,36:95-109
[4] Rahman I,MacNee W. Lung glutathione and oxidative stress: Implications in cigarette smoke-induced airways disease. Am J Physiol,1999,277:L1067- L1088
[5] Rahman I,MacNee W. Oxidative stress and regulation of glutathione synthesis in lung inflammation. Eur Respir J,2000,16:534-554
[6] Rahman I,MacNee W. Role of transcription factors in inflammatory lung diseases. Thorax, 1998,53:601-612
[7] Rahman I,MacNee W. Role of oxidants/antioxidants in smoking-induced airways diseases. Free Rad Biol Med, 1996,21:669-681
[8] Rahman I ,MacNee W. Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med,2000,28:1405-1420
[9] Zang LY, Stone K,Pryor WA. Detection of free radicals in aqueous extracts of cigarette tar by electron spin resonance. Free Radic Biol Med,1995,19:161-167
[10] Rochelle LG, Fischer BM,Adler KB. Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro. Free Radic Biol Med,1998,24:863-868
[11] Parola M, Bellomo G, Robino G, et al. 4-Hydroxynonenal as a biological signal:molecular basis and pathophysiological implications. Antioxid Redox Signalling, 1999,1:255-284
[12] Uchida K, Shiraishi M, Naito Y, et al. Activation of stress signaling pathways by the end product of lipid peroxidation. J Biol Chem,1999,274:2234-2242
[13] Rahman I, Mulier B, Gilmour PS,et al. Oxidant-mediated lung epithelial cell tolerance: the role of intracellular glutathione and nuclear factor-kappaB.Biochem Pharmacol,2001,62:787-794
[14] Kamata H, Manabe T, Oka S, et al. Hydrogen peroxide activates IkappaB kinases through phosphorylation of serine residues in the activation loops. FEBS Lett,2002,519(1-3):231-237
[15] Takada Y,Mukhopadhyay A, Kundu GC, et al. Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase. J Biol Chem,2003,278(26):24233-24241
[16] Di Stefano A, Caramori G, Oates T,et al. Increased expression of uclear factor KB in bronchial biopsies from smokers and patients w ith COPD. Eur Respir J ,2002,20:556-563
[17] Parmentier M,Drost E,Hirani N,et al.Thiol antioxidants inhibit neutrophil chemotaxis by decreasing release of IL-8 from macrophages and pulmonary epithelia cells. Am J Respir Crit Care Med, 1999,159:A286
[18] Iles KE, Dickinson DA, Watanabe N,et al. AP-1 activation through endogenous H_2O_2 generation by alveolar macrophages. Free Radic Biol Med,2002,32(12):1304-1313
[19] Li DW, Spector A. Hydrogen peroxide-induced expression of the proto-oncogenes, c-jun, c-fos and c-myc in rabbit lens epithelial cells. Mol Cell Biochem, 1997,173(1 -2):59-69
[20] Nicholson WJ, Slight J, Donaldson K. Inhibition of the transcription factors NF-kappa B and AP-1 underlies loss of cytokine gene expression inrat alveolarmacrophages treated with adiffusible product from the spores of Aspergillus fumigatus. Am J Respir Cell Mol Biol,1996,15(1):88-96
[21] Zhou L, Tan A, Iasvovskaia S,et al, Hershenson MB. Ras and mitogen-activated protein kinase kinasekinase-1 coregulate activator protein-1 and nuclear factor-kappaB-mediated gene expression in air-way epithelial cells. Am J Respir Cell Mol Biol,2003,28(6):762-769
[22] Kasielski M , Nowak D. Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir Med,2001,95:448-456
[23] Wu C. Chromatin remodeling and the control of gene expression. J Biol Chem, 1997,272(45):28171 -28174
[24] Rahman I, Marwick J, Kirkham P. Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol,2004,68(6):1255-1267
[25] Grunstein M. Histone acetylation in chromatin structure and transcription.Nature, 1997,389(6649): 349-352
[26] Eberharter A, Becker PB. Histone acetylation: a switch between repressive and permissive chromatin: Second in review series on chromatin dynamics. EMBO Rep,2002,3: 224-229
[27] Hasan S, Hottiger MO. Histone acetyltransferases: a role in DNA repair and DNA replication. J Mol Med,2002,80:463-474
[28] Gao L, Cueto MA, Asselbergs F, et al. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem, 2002,277:25748-25755
[29] Grozinger CM, Schreiber SL. Deacetylase enzymes: biological functions and the use of small-molecule inhibitors.Chem Biol, 2002,9(1): 13-16
[30] Rahman I, Gilmour PS, Jimenez LA, MacNee W. Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation. Mol Cell Biochem,2002,234-235(1-2):239-48
[31] Tomita K, Barnes PJ, Adcock IM. The effect of oxidative stress on histone acetylation and IL-8 release. Biochem Biophys Res Commun,2003 ;301(2):572-577
[32] Moodie FM, Marwick JA, Anderson CS, et al. Oxidative stress and cigarette smoke alter chromatin remodeling but differentially regulate NF-kappaB activation and proinflammatory cytokine release in alveolar epithelial cells.FASEB J,2004,18(15): 1897-1899
[33] Ito K, Hanazawa T, Tomita K,et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun,2004,315(1):240-245
[34] Sugiura H, Ichinose M, Tomaki M, et al. Quantitative assessment of protein-bound tyrosine nitration in airway secretions from patients with inflammatory airway disease. Free Radic Res,2004,38(1):49-57
[35] Muegge K. Preparing the target for the bullet. Nat Immun,2002,3: 16-17
[36] Saccani S, Pantano S, Natoli G. p38-dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat Immun,2002,3: 69-75
[37] Sambucetti LC, Fischer DD, Zabludoff S,et al. Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem, 1999,274:34940-34947
[38] Berghe WV, Bosscher KD, Boone Eet al.The nuclear factor-κB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter.J Biol Chem, 1999,274: 32091-32098
[39] Fusunyan RD, Quinn JJ, Fujimoto M, et al. Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.Mol Med,1999,5:631-640
[40] Pender SLF, Quinn JJ, Sanderson IR, et al. Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells.Am J Physiol Gastrointest Liver Physiol.2000,279: G918-G924
[41] Ito K, Lim G, Caramori G,et al. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J,2001,15:1110-1112
[42] Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin- 1 beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol,2000,20(18):6891-6903
[43] Chen L, Fischle W, Verdin E, et al. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science,2001,293(5535):1653-1657
[44] Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol,2004,31(6):633-642
[45] Ito K, Ito M, Elliott WM, et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med,2005,352(19):1967-1976
[46] Ito K, Lim S, Caramori G,et al. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages.FASEB J,2001,15(6):1110-1112
[47] Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med ,2002,166(3):392-396
[48] Barnes PJ, Adcock IM, Ito K. Histone acetylation and deacetylation: importance in inflammatory lung diseases. Eur Respir J, 2005,25(3):552-563
[49] Higashimoto Y,Elliott W M ,Behzad AR,et al. Inflammatory mediator mRNA expression by adenovirus EIA transfected bronchial epithelial cells. Am J Respir Crit Care Med,2002,166:200-207
[50] Hogg JC. Role of latent viral infections in chronic obstructive pulmonary disease and asthma. Am J Respir Crit Care Med,2001,164:71 —75
[51] Kyriakis J M , Avruch J . Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev,2001,81 (2): 807-869
[52] Goodyear LJ,Chang PY,Sherwood DJ,et al. Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletalmuscle. Am J Physiol,1996,271(2Pt1):E403-E408
[53] Christian Widmann. Mitogen—activated protein kinase:Conservation of a three . kinase module from yeast to human . Physiological Reviews,1999,79(1):143-180
[54] Stockley RA. Neutrophils and the pathogenesis of COPD. Chest,2002,121(5 Suppl):151S-155S
[55] Barnes PJ. Alveolar macrophages in chronic obstructive pulmonary disease [COPD]. Cell Mol Biol,2004,50:OL627-637
[56] Tamura DY, Moore EE, Johnson JL,et al. p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary microvascular endothelial cells. Surgery, 1998,124(2):403-407
[57] Nick JA, Young SK, Brown KK, et al. Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation. J Immunol,2000,164(4):2151-2159
[58] Underwood DC, Osborn RR, Bochnowicz S, et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol,2000,279(5): L895-902
[59] Mercer B, Kolesnikova N, Sonett J, D'Armiento J. Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke. J Biol Chem,2004,279(17):17690-17696
[60] Milligan SA, Owens MW, Grisham MB. Differential regulation of extracellular signal-regulated kinase and nuclear factor-kappa B signal transduction pathways by hydrogen peroxide and tumor necrosis factor. Arch Biochem Biophys,1998,352(2):255-262
[61] Jope RS, Zhang L, Song L. Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells. Arch Biochem Biophys,2000,376(2):365-370
[62] Lee K, Esselman WJ. Inhibition of PTPs by H2O2 regulates the activation of distinct MAPK pathways. Free Radic Biol Med,2002,33(8):l 121-1132
[63] Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy.Oncogene,2000,19(56):6550-6565
[64] Chen K, Vita JA, Berk BC,et al. c-Jun N-terminal kinase activation by hydrogen peroxide in endothelial cells involves SRC-dependent epidermal growth factor receptor transactivation. J Biol Chem,2001,276(19):16045-16050
[65] Zhuang S, Schnellmann RG. H_2O_2-induced transactivation of EGF receptor requires Src and mediates ERK1/2, but not Akt, activation in renal cells. Am J Physiol Renal Physiol,2004,286(5):F858-865
[66] Rhee SG, Chang TS, Bae YS,et al. Cellular regulation by hydrogen peroxide. J Am Soc Nephrol,2003,14(8 Suppl 3):S211-215
[67] Whitmarsh A J, R J Davis. Regulation of transcription factor function by phosphorylation. Cell Mol Life Sci, 2000,57:1172-1183
[68] Janknecht R, Nordheim A. MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. Biophys Res Commun, 1996,228:831-837.
[69] Yvonne M W Janssen-Heiningerjan Macara, Brooke T Mossman. Cooperativity between oxidants and tumor necrosis factor in the activation of Nuclear Factor(NF)-κB. American Journal of Respiratory Cell and Molecular Biology, 1999,20:5
[70] Mossman BT, Lounsbury KM, Reddy SP. Oxidants and signaling by mitogen-activated protein kinases in lung epithelium. Am J Respir Cell Mol Biol,2006,34(6):666-669
[71] Tikoo K, Lau SS,and Monks TJ. Histone H3 phosphorylation is coupled to poly-(ADP-ribosylation)during reactive oxygen species-induces cell death in renal proximal tubular epithelial cells. Mol Pharmacol,2001,60:394-402
[72] Thomson S, Mahadevan LC, Clayton AL. MAP kinase-mediated signalling to nucleosomes and immediate-early gene induction. Semin Cell Dev Biol,1999,10:205-214
[73] Adler V, Yin Z, Tew KD,et al. Role of redox potential and reactive oxygen species in stress signaling. Oncogene,1999,18:6104-6111
[74] Kawasaki H, Schiltz L, Chiu R,et al. ATF-2 has instrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature,2000,405:195-200
[75] Saccani S, S Pantano, G Natoli. p38-Dependent marking of inflammatory genes for increased NF-κB recruitment. Nat Immunol,2002,3: 69-75
[76] Miyata Y, Towatari M, Maeda T,et al. Histone acetylation induces by granulocyte colony stimulating factor in a MAP kinase-dependent manner. Biochemical and Biophysical Research Communications,2001,283 :655-660
[77] Barnes PJ ,Pauwels RA. Theophylline in the management of asthma: time for reappraisal?Eur Respir J. 1994,7(3):579-591
[78] Rabe KF, Magnussen H ,Dent G. Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants. Eur Respir J,1995,8:637-642
[79] Markham A, Faulds D. Theophylline:A review of its potential steroid sparing effects in asthma. Drugs, 1998,56:1081-1091
[80] Rabe KF,Dent G. Theophylline and airway inflammation. Clin Exp Allergy,1998,28(Suppl 3):35-41
[81] Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med,2003,167:813-818
[82] Culpitt SV, de Matos C, Russell RE, et al. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease.Am J Respir Crit Care Med ,2002,165:1371-1376
[83] Kobayashi M, Nasuhara Y, Betsuyaku T, et al. Effect of lowdose theophylline on airway inflammation in COPD. Respirology,2004,9:249-254
[84] Cosio BG, Tsaprouni L , Ito K . Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med ,2004,200 :689-695
[85] Ito K, Lim S, Caramori G,et al.A molecular mechanism of action of theophylline:induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA ,2002,99:8921-8926
[2] Sternglanz R. Histone acetylation: a gateway to transcriptional activation.Trends Biol Sci,1996,21 :357-358
[3] Urnov FD, Wolffe AP. Chromatin remodeling and transcriptional activation: the cast (in order of appearance). Oncogene,2001,20:2991-3006
[4] Walia H, Chen H,Sun JM,et al. Histone acetylation is required to maintain the unfolded nucleosome structure associated with transcribing DNA. J Biol Chem,1998,273,14516-14522
[5] Sambucetti LC, Fischer DD, Zabludoff S,et al. Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem, 1999,274:34940-34947
[6] Grunstein, M. Histone acetylation in chromatin structure and transcription.Nature, 1997,389:349-352
[7] Rahman I, Gilmour PS, Jimenez LA, MacNee W. Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation. Mol Cell Biochem,2002,234-235(1-2):239-248
[8] Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol,2004,31(6):633-642
[9] MacNee W.Oxidative stress and lung inflammation in airways disease. Eur J Pharmacol,2001,429(1-3): 195-207
[10] Tikoo K, Lau SS,Monks TJ. Histone H3 phosphorylation is coupled to poly-(ADP-ribosylation)during reactive oxygen species-induces cell death in renal proximal tubular epithelial cells. Mol Pharmacol,2001, 60:394-402
[11] Thomson S, Mahadevan LC, Clayton AL. MAP kinase-mediated signalling to nucleosomes and immediate-early gene induction.Semin Cell Dev Bio,1999,10:205-214
[12]Saccani SS,Pantano,G Natoli.p38-Dependent marking of inflammatory genes for increased NF-κB recruitment.Nat Immunol,2002,3:69-75
[13]Miyata Y,Towatari M,Maeda T,et al.Histone acetylation induces by granulocyte colony stimulating factor in a MAP kinase-dependent manner.Biochemical and Biophysical Research Communications,2001,283:655-660
[14]Barnes PJ.Yheophylline:new perspectives for an old drug.Am J Respir Crit Care Med,2003,167:813-818
[15]Culpitt SV,de Matos C,Russell RE,et al.Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2002,165:1371-137
[16]Kobayashi M,Nasuhara Y,Betsuyaku T,et al.Effect of low dose theophylline on airway inflammation in COPD.Respirology,2004,9:249-254
[17]Cosio BG,Tsaprouni L,Ito K.Theophylline restores historic deacetylase activity and steroid responses in COPD macrophages.J Exp Med,2004,200:689-695
[18]Ito K,Lim S,Caramori G,et al.A molecular mechanism of action of theophylline:induction of histone deacetylase activity to decrease inflammatory gene expression.Proc Natl Acad Sci,2002,99:8921-8926
[19]Eberharter A,Becker PB.Histone acetylation:a switch between repressive and permissive chromatin:Second in review series on chromatin dynamics.EMBO Rep,2002,3:224-229
[20]Grunstein M.Histone acetylation in chromatin structure and transcription.Nature,1997,389(6649):349-352
[21]Hoffmann E,Dittrich-Breiholz O,Holtmann H,Kracht M.Multiple control of interleukin-8 gene expression.J Leukoc Biol,2002,72:847-855
[22]周青,贺菊乔,刘丽芳,等.紫金胶囊对细菌性前列腺炎模型大鼠炎性因子TNF-α及IL-8的作用.中国中西医结合外科杂志,2005,(11):56-58
[23]陈红梅,罗百灵,屈满英,等.红霉素对慢性阻塞性肺疾病大鼠基质金属蛋白酶-9的影响.中华结核和呼吸杂志,2008,31(9):702-703
[24]宋一平,崔德健,茅培英,等.慢性阻塞性肺疾病大鼠模型气道重塑及生长因子的研究.中华结核和呼吸杂志,2001,24:283-287
[25]邢传平,刘斌,董亮.免疫组织化学标记结果的判断方法.中华病理学杂志,2001,30(4):318
[26]Marwick JA,Kirkham PA,Stevenson CS,et al.Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs.American Journal of Respiratory Cell and Molecular Biology.2004,31:633-642
[27]Pauwels RA,B Soina,PMA Claverley,et al.Global strategy for the diagnosis,management,and prevention of chronic obstructive pulmonary disease.Am J Respir Crit Care Med,2001,163:1256-1276.
[28]Rahman I,MacNee W.Lung glutathione and oxidative stress:implications in cigarette smoke-induced airways disease.Am J Physiol,1999,227,L 1067-L 1088
[29]Rahman I,MacNee W.Oxidative stress and regulation of glutathione synthesis in lung inflammation.Eur Respir J,2000,16:534-554
[30]Rahman I,MacNee W.The role of transcription factors in inflammatory lung diseases.Thorax,1998,53:601-612
[31]Rahman I.Oxidative stress,chromatin remodelling and gene transcription in inflammation and chronic lung disease.J Biochem Mol Biol,2003,36:95-109
[32]Barnes P J,Karin M.Nuclear factor-κB:a pivotal transcription factor in chronic inflammatory diseases.New Engl J Med,1997,336:1066-1071
[33]Wright JG,Christman JW.The role of nuclear factor κB in the pathogenesis of pulmonary diseases:implications for therapy.Am J Respir Med,2003,2:211-219
[34]Rahman I,W MacNee.Lung glutathione and oxidative stress:implications in cigarette smoke-induced airways disease.Am J Physiol,1999,227:L1067-L1088
[35]Church T,VA Pryor.Free radical chemistry of cigarette smoke and its toxicological implications.Environ Health Perspect,1985,46:111-126
[36]Imhof A,Wolffe AP.Transcription:gene control by targeted histone acetylation.Curr Biol,1998,8:R422-R424
[37] De Ruijter AJ, Van Gennip AH, Caron HN,et al. Histone deacetylases (HDACs):characterization of classical HDAC family.Biochem J,2003,370: 737-749
[38] Johnson CA, Turner BM. Histone deacetylase: complex transducers of nuclear signals. Cell Develop Biol,1999,10: 179-188
[39] Ito K, Lim S, Caramori G,et al. Cigarette smokingreduces histone deacetylase 2 xpression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J,2001,15: 1110-1112
[40] Berghe WV, Bosscher KD, Boone E, Plaisance S, Haegeman G: The nuclear factor-kB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter.J Biol Chem, 1999,274: 32091-32098
[41] Fusunyan RD, Quinn JJ, Fujimoto M, et al. Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.Mol Med, 1999,5: 631-640
[42] Pender SLF, Quinn JJ, Sanderson IR, MacDonald TT: Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells.Am J Physiol Gastrointest Liver Physiol,2000,279: G918-G924
[43] Y Elliott WM, Ito M. Total histone deacetylase activity decreases with increasing clinical stage of COPD. Am J Respir Crit Care Med,2004,169: 276
[44] Ito K, Ito M, Elliott WM, et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med,2005,352(19):1967-1976
[45] Ito K, Hanazawa T, Tomita K, et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun,2004,315(1):240-245
[46] Ischiropoulos H. Biological selectivity and functional aspects of protein tyrosine nitration. Biochem Biophys Res Commun,2003,305: 777-783
[47] Kramer OH, Zhu P, Ostendorff HP, et al. The histone deacetylase inhibitor valproic acid selectively induces proteasomal degradation of HDAC2. EMBO J,2003,22:3411-3420
[48]Bames PJ,Pauwels RA.Theophylline in the management of asthma:time for reappraisal ? Eur Respir J,1994,7(3):579-591
[49]Rabe KF,Magnussen H,Dent G.Yheophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants.Eur Respir J,1995,8(4):637-642
[50]Markham A,Faulds D.Theophylline.A review of its potential steroid sparing effects in asthma.Drugs,1998,56(6):1081-1091
[51]Rabe KF,Dent G.Theophylline and airway inflammation.Clin Exp Allergy,1998,28(Suppl 3):35-41
[52]吕小琴,唐法娣.p38MAPK特异性抑制剂SB239063.国外医学呼吸系统分册,2004,24(1):38-39
[53]Chen K,Vita JA,Berk BC,et al.c-Jun N-terminal kinase activation by hydrogen peroxide in endothelial cells involves SRC-dependent epidermal growth factor receptor transactivation.J Biol Chem,2001,276(19):16045-16050
[54]Zhuang S,Schnellmann RG.H_2O_2-induced transactivation of EGF receptor requires Src and mediates ERK1/2,but not Akt,activation in renal cells.Am J Physiol Renal Physiol,2004,286(5):F858-F865
[55]Whitmarsh AJ,RJ Davis.Regulation of transcription factor function by phosphorylation.Cell Mol Life Sci,2000,57:1172-1183
[56]Janknecht R,Nordheim A.MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP.Biophys Res Commun,1996,228:831-837
[57]Baeza-Squiban A,Bonvallot V,Boland S,et al.Airborne particles evoke an inflammatory response in human airway epithelium.Activation of transcription factors.Cell Biol Toxicol,1999,15:375-380
[58]Hellermann GR,Nagy SB,Koong X,et al.Mechanisms of cigarette smoke condensate-induced acute inflammatory response in human bronchial epithelial cells.Respir Res,2002,3:22-29
[59]屈满英,罗百灵,陈红梅,等.分泌型白细胞蛋白酶抑制剂对香烟烟雾提取物诱导人支气管上皮细胞炎症介质表达的影响.中华结核和呼吸杂志,2008,31(5):352-355
[60]Moodie FM,Marwick JA,Anderson CS,et al.Oxidative stress and cigarette smoke alter chromatin remodeling but differentially regulate NF-κB activation and proinflammatory cytokine release in alveolar epithelial cells.The FASEB Journal,2004,18(15):1897-1899
[61] Hortense Slevogt, Bernd Schmeck, Carola Jonatat,et al. Moraxella catarrhalis induces inflammatory response of bronchial epithelial cells via MAPK and NF-κB activation and histone deacetylase activity reduction. Am J Physiol Lung Cell Mol Physiol,2006,290: L818-L826
[62] Pryor WA, Stone K. Oxidants in cigarette smoke: radicals, hydrogen peroxides, peroxynitrate, and peroxynitrite. Ann NY Acad Sci, 1993,686:12-28
[63] Mio T, Romberger DJ , Thompson AB , et al . Cigarette smoke induces interleukin-8 release from human bronchial epithelial cells. AmJ Respir Crit Care Med,1997,155:1770-1776
[64] Goodyear LJ,Chang PY,Sherwood DJ,et al. Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletalmuscle. Am J Physiol, 1996,271(2Pt1):E403-E408
[65] Mercer B, Kolesnikova N, Sonett J, D'Armiento J. Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke. J Biol Chem,2004,279(17):17690-17696
[66] Milligan SA, Owens MW, Grisham MB. Differential regulation of extracellular signal-regulated kinase and nuclear factor-kappa B signal transduction pathways by hydrogen peroxide and tumor necrosis factor. Arch Biochem Biophys,1998,352(2):255-262
[67] Jope RS, Zhang L, Song L. Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells. Arch Biochem Biophys,2000,376(2):365-370
[68] Lee K, Esselman WJ. Inhibition of PTPs by H2O2 regulates the activation of distinct MAPK pathways. Free Radic Biol Med,2002,33(8):1121-1132
[69] Tamura DY, Moore EE, Johnson JL,et al. p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary microvascular endothelial cells. Surgery, 1998,124(2):403-407,discussion 408
[70] Nick JA, Young SK, Brown KK, et al. Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation. J Immunol, 2000,164(4):2151-2159
[71] Underwood DC, Osborn RR, Bochnowicz S, et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol,2000,279(5):L895-L902
[72] Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene,2000,19(56):6550-6565
[73] Rhee SG, Chang TS, Bae YS, et al. Cellular regulation by hydrogen peroxide. J Am Soc Nephrol 2003,14(8 Suppl 3):S211-5.
[74] Kawasaki H, Schiltz L, Chiu R,et al. ATF-2 has instrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature,2000,405:195-200
[75] Adler V, Yin Z, Tew KD,Ronai, Z. Role of redox potential and reactive oxygen species in stress signaling. Oncogene,1999,18:6104-6111
[1] Rahman I, W MacNee. Lung glutathione and oxidative stress: implications in cigarette smoke-induced airways disease. Am J Physiol, 1999,227:L1067-L1088
[2] Church T VA Pryor. Free radical chemistry of cigarette smoke and its toxicological implications. Environ. Health Perspect, 1985,46:111-126
[3] Rahman I. Oxidative stress, chromatin remodelling and gene transcription in inflammation and chronic lung disease. J Biochem Mol Biol,2003,36:95-109
[4] Rahman I,MacNee W. Lung glutathione and oxidative stress: Implications in cigarette smoke-induced airways disease. Am J Physiol,1999,277:L1067- L1088
[5] Rahman I,MacNee W. Oxidative stress and regulation of glutathione synthesis in lung inflammation. Eur Respir J,2000,16:534-554
[6] Rahman I,MacNee W. Role of transcription factors in inflammatory lung diseases. Thorax, 1998,53:601-612
[7] Rahman I,MacNee W. Role of oxidants/antioxidants in smoking-induced airways diseases. Free Rad Biol Med, 1996,21:669-681
[8] Rahman I ,MacNee W. Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med,2000,28:1405-1420
[9] Zang LY, Stone K,Pryor WA. Detection of free radicals in aqueous extracts of cigarette tar by electron spin resonance. Free Radic Biol Med,1995,19:161-167
[10] Rochelle LG, Fischer BM,Adler KB. Concurrent production of reactive oxygen and nitrogen species by airway epithelial cells in vitro. Free Radic Biol Med,1998,24:863-868
[11] Parola M, Bellomo G, Robino G, et al. 4-Hydroxynonenal as a biological signal:molecular basis and pathophysiological implications. Antioxid Redox Signalling, 1999,1:255-284
[12] Uchida K, Shiraishi M, Naito Y, et al. Activation of stress signaling pathways by the end product of lipid peroxidation. J Biol Chem,1999,274:2234-2242
[13] Rahman I, Mulier B, Gilmour PS,et al. Oxidant-mediated lung epithelial cell tolerance: the role of intracellular glutathione and nuclear factor-kappaB.Biochem Pharmacol,2001,62:787-794
[14] Kamata H, Manabe T, Oka S, et al. Hydrogen peroxide activates IkappaB kinases through phosphorylation of serine residues in the activation loops. FEBS Lett,2002,519(1-3):231-237
[15] Takada Y,Mukhopadhyay A, Kundu GC, et al. Hydrogen peroxide activates NF-kappa B through tyrosine phosphorylation of I kappa B alpha and serine phosphorylation of p65: evidence for the involvement of I kappa B alpha kinase and Syk protein-tyrosine kinase. J Biol Chem,2003,278(26):24233-24241
[16] Di Stefano A, Caramori G, Oates T,et al. Increased expression of uclear factor KB in bronchial biopsies from smokers and patients w ith COPD. Eur Respir J ,2002,20:556-563
[17] Parmentier M,Drost E,Hirani N,et al.Thiol antioxidants inhibit neutrophil chemotaxis by decreasing release of IL-8 from macrophages and pulmonary epithelia cells. Am J Respir Crit Care Med, 1999,159:A286
[18] Iles KE, Dickinson DA, Watanabe N,et al. AP-1 activation through endogenous H_2O_2 generation by alveolar macrophages. Free Radic Biol Med,2002,32(12):1304-1313
[19] Li DW, Spector A. Hydrogen peroxide-induced expression of the proto-oncogenes, c-jun, c-fos and c-myc in rabbit lens epithelial cells. Mol Cell Biochem, 1997,173(1 -2):59-69
[20] Nicholson WJ, Slight J, Donaldson K. Inhibition of the transcription factors NF-kappa B and AP-1 underlies loss of cytokine gene expression inrat alveolarmacrophages treated with adiffusible product from the spores of Aspergillus fumigatus. Am J Respir Cell Mol Biol,1996,15(1):88-96
[21] Zhou L, Tan A, Iasvovskaia S,et al, Hershenson MB. Ras and mitogen-activated protein kinase kinasekinase-1 coregulate activator protein-1 and nuclear factor-kappaB-mediated gene expression in air-way epithelial cells. Am J Respir Cell Mol Biol,2003,28(6):762-769
[22] Kasielski M , Nowak D. Long-term administration of N-acetylcysteine decreases hydrogen peroxide exhalation in subjects with chronic obstructive pulmonary disease. Respir Med,2001,95:448-456
[23] Wu C. Chromatin remodeling and the control of gene expression. J Biol Chem, 1997,272(45):28171 -28174
[24] Rahman I, Marwick J, Kirkham P. Redox modulation of chromatin remodeling: impact on histone acetylation and deacetylation, NF-kappaB and pro-inflammatory gene expression. Biochem Pharmacol,2004,68(6):1255-1267
[25] Grunstein M. Histone acetylation in chromatin structure and transcription.Nature, 1997,389(6649): 349-352
[26] Eberharter A, Becker PB. Histone acetylation: a switch between repressive and permissive chromatin: Second in review series on chromatin dynamics. EMBO Rep,2002,3: 224-229
[27] Hasan S, Hottiger MO. Histone acetyltransferases: a role in DNA repair and DNA replication. J Mol Med,2002,80:463-474
[28] Gao L, Cueto MA, Asselbergs F, et al. Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family. J Biol Chem, 2002,277:25748-25755
[29] Grozinger CM, Schreiber SL. Deacetylase enzymes: biological functions and the use of small-molecule inhibitors.Chem Biol, 2002,9(1): 13-16
[30] Rahman I, Gilmour PS, Jimenez LA, MacNee W. Oxidative stress and TNF-alpha induce histone acetylation and NF-kappaB/AP-1 activation in alveolar epithelial cells: potential mechanism in gene transcription in lung inflammation. Mol Cell Biochem,2002,234-235(1-2):239-48
[31] Tomita K, Barnes PJ, Adcock IM. The effect of oxidative stress on histone acetylation and IL-8 release. Biochem Biophys Res Commun,2003 ;301(2):572-577
[32] Moodie FM, Marwick JA, Anderson CS, et al. Oxidative stress and cigarette smoke alter chromatin remodeling but differentially regulate NF-kappaB activation and proinflammatory cytokine release in alveolar epithelial cells.FASEB J,2004,18(15): 1897-1899
[33] Ito K, Hanazawa T, Tomita K,et al. Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration. Biochem Biophys Res Commun,2004,315(1):240-245
[34] Sugiura H, Ichinose M, Tomaki M, et al. Quantitative assessment of protein-bound tyrosine nitration in airway secretions from patients with inflammatory airway disease. Free Radic Res,2004,38(1):49-57
[35] Muegge K. Preparing the target for the bullet. Nat Immun,2002,3: 16-17
[36] Saccani S, Pantano S, Natoli G. p38-dependent marking of inflammatory genes for increased NF-kappa B recruitment. Nat Immun,2002,3: 69-75
[37] Sambucetti LC, Fischer DD, Zabludoff S,et al. Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J Biol Chem, 1999,274:34940-34947
[38] Berghe WV, Bosscher KD, Boone Eet al.The nuclear factor-κB engages CBP/p300 and histone acetyltransferase activity for transcriptional activation of the interleukin-6 gene promoter.J Biol Chem, 1999,274: 32091-32098
[39] Fusunyan RD, Quinn JJ, Fujimoto M, et al. Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation.Mol Med,1999,5:631-640
[40] Pender SLF, Quinn JJ, Sanderson IR, et al. Butyrate upregulates stromelysin-1 production by intestinal mesenchymal cells.Am J Physiol Gastrointest Liver Physiol.2000,279: G918-G924
[41] Ito K, Lim G, Caramori G,et al. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages. FASEB J,2001,15:1110-1112
[42] Ito K, Barnes PJ, Adcock IM. Glucocorticoid receptor recruitment of histone deacetylase 2 inhibits interleukin- 1 beta-induced histone H4 acetylation on lysines 8 and 12. Mol Cell Biol,2000,20(18):6891-6903
[43] Chen L, Fischle W, Verdin E, et al. Duration of nuclear NF-kappaB action regulated by reversible acetylation. Science,2001,293(5535):1653-1657
[44] Marwick JA, Kirkham PA, Stevenson CS, et al. Cigarette smoke alters chromatin remodeling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol,2004,31(6):633-642
[45] Ito K, Ito M, Elliott WM, et al. Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med,2005,352(19):1967-1976
[46] Ito K, Lim S, Caramori G,et al. Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages.FASEB J,2001,15(6):1110-1112
[47] Ito K, Caramori G, Lim S, et al. Expression and activity of histone deacetylases in human asthmatic airways. Am J Respir Crit Care Med ,2002,166(3):392-396
[48] Barnes PJ, Adcock IM, Ito K. Histone acetylation and deacetylation: importance in inflammatory lung diseases. Eur Respir J, 2005,25(3):552-563
[49] Higashimoto Y,Elliott W M ,Behzad AR,et al. Inflammatory mediator mRNA expression by adenovirus EIA transfected bronchial epithelial cells. Am J Respir Crit Care Med,2002,166:200-207
[50] Hogg JC. Role of latent viral infections in chronic obstructive pulmonary disease and asthma. Am J Respir Crit Care Med,2001,164:71 —75
[51] Kyriakis J M , Avruch J . Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev,2001,81 (2): 807-869
[52] Goodyear LJ,Chang PY,Sherwood DJ,et al. Effects of exercise and insulin on mitogen-activated protein kinase signaling pathways in rat skeletalmuscle. Am J Physiol,1996,271(2Pt1):E403-E408
[53] Christian Widmann. Mitogen—activated protein kinase:Conservation of a three . kinase module from yeast to human . Physiological Reviews,1999,79(1):143-180
[54] Stockley RA. Neutrophils and the pathogenesis of COPD. Chest,2002,121(5 Suppl):151S-155S
[55] Barnes PJ. Alveolar macrophages in chronic obstructive pulmonary disease [COPD]. Cell Mol Biol,2004,50:OL627-637
[56] Tamura DY, Moore EE, Johnson JL,et al. p38 mitogen-activated protein kinase inhibition attenuates intercellular adhesion molecule-1 up-regulation on human pulmonary microvascular endothelial cells. Surgery, 1998,124(2):403-407
[57] Nick JA, Young SK, Brown KK, et al. Role of p38 mitogen-activated protein kinase in a murine model of pulmonary inflammation. J Immunol,2000,164(4):2151-2159
[58] Underwood DC, Osborn RR, Bochnowicz S, et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am J Physiol Lung Cell Mol Physiol,2000,279(5): L895-902
[59] Mercer B, Kolesnikova N, Sonett J, D'Armiento J. Extracellular regulated kinase/mitogen activated protein kinase is up-regulated in pulmonary emphysema and mediates matrix metalloproteinase-1 induction by cigarette smoke. J Biol Chem,2004,279(17):17690-17696
[60] Milligan SA, Owens MW, Grisham MB. Differential regulation of extracellular signal-regulated kinase and nuclear factor-kappa B signal transduction pathways by hydrogen peroxide and tumor necrosis factor. Arch Biochem Biophys,1998,352(2):255-262
[61] Jope RS, Zhang L, Song L. Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells. Arch Biochem Biophys,2000,376(2):365-370
[62] Lee K, Esselman WJ. Inhibition of PTPs by H2O2 regulates the activation of distinct MAPK pathways. Free Radic Biol Med,2002,33(8):l 121-1132
[63] Mendelsohn J, Baselga J. The EGF receptor family as targets for cancer therapy.Oncogene,2000,19(56):6550-6565
[64] Chen K, Vita JA, Berk BC,et al. c-Jun N-terminal kinase activation by hydrogen peroxide in endothelial cells involves SRC-dependent epidermal growth factor receptor transactivation. J Biol Chem,2001,276(19):16045-16050
[65] Zhuang S, Schnellmann RG. H_2O_2-induced transactivation of EGF receptor requires Src and mediates ERK1/2, but not Akt, activation in renal cells. Am J Physiol Renal Physiol,2004,286(5):F858-865
[66] Rhee SG, Chang TS, Bae YS,et al. Cellular regulation by hydrogen peroxide. J Am Soc Nephrol,2003,14(8 Suppl 3):S211-215
[67] Whitmarsh A J, R J Davis. Regulation of transcription factor function by phosphorylation. Cell Mol Life Sci, 2000,57:1172-1183
[68] Janknecht R, Nordheim A. MAP kinase-dependent transcriptional coactivation by Elk-1 and its cofactor CBP. Biophys Res Commun, 1996,228:831-837.
[69] Yvonne M W Janssen-Heiningerjan Macara, Brooke T Mossman. Cooperativity between oxidants and tumor necrosis factor in the activation of Nuclear Factor(NF)-κB. American Journal of Respiratory Cell and Molecular Biology, 1999,20:5
[70] Mossman BT, Lounsbury KM, Reddy SP. Oxidants and signaling by mitogen-activated protein kinases in lung epithelium. Am J Respir Cell Mol Biol,2006,34(6):666-669
[71] Tikoo K, Lau SS,and Monks TJ. Histone H3 phosphorylation is coupled to poly-(ADP-ribosylation)during reactive oxygen species-induces cell death in renal proximal tubular epithelial cells. Mol Pharmacol,2001,60:394-402
[72] Thomson S, Mahadevan LC, Clayton AL. MAP kinase-mediated signalling to nucleosomes and immediate-early gene induction. Semin Cell Dev Biol,1999,10:205-214
[73] Adler V, Yin Z, Tew KD,et al. Role of redox potential and reactive oxygen species in stress signaling. Oncogene,1999,18:6104-6111
[74] Kawasaki H, Schiltz L, Chiu R,et al. ATF-2 has instrinsic histone acetyltransferase activity which is modulated by phosphorylation. Nature,2000,405:195-200
[75] Saccani S, S Pantano, G Natoli. p38-Dependent marking of inflammatory genes for increased NF-κB recruitment. Nat Immunol,2002,3: 69-75
[76] Miyata Y, Towatari M, Maeda T,et al. Histone acetylation induces by granulocyte colony stimulating factor in a MAP kinase-dependent manner. Biochemical and Biophysical Research Communications,2001,283 :655-660
[77] Barnes PJ ,Pauwels RA. Theophylline in the management of asthma: time for reappraisal?Eur Respir J. 1994,7(3):579-591
[78] Rabe KF, Magnussen H ,Dent G. Theophylline and selective PDE inhibitors as bronchodilators and smooth muscle relaxants. Eur Respir J,1995,8:637-642
[79] Markham A, Faulds D. Theophylline:A review of its potential steroid sparing effects in asthma. Drugs, 1998,56:1081-1091
[80] Rabe KF,Dent G. Theophylline and airway inflammation. Clin Exp Allergy,1998,28(Suppl 3):35-41
[81] Barnes PJ. Theophylline: new perspectives for an old drug. Am J Respir Crit Care Med,2003,167:813-818
[82] Culpitt SV, de Matos C, Russell RE, et al. Effect of theophylline on induced sputum inflammatory indices and neutrophil chemotaxis in chronic obstructive pulmonary disease.Am J Respir Crit Care Med ,2002,165:1371-1376
[83] Kobayashi M, Nasuhara Y, Betsuyaku T, et al. Effect of lowdose theophylline on airway inflammation in COPD. Respirology,2004,9:249-254
[84] Cosio BG, Tsaprouni L , Ito K . Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med ,2004,200 :689-695
[85] Ito K, Lim S, Caramori G,et al.A molecular mechanism of action of theophylline:induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA ,2002,99:8921-8926