炎症因子Daintain/AIF-1对胰腺β细胞功能影响的研究
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摘要
Daintain(大炎肽)是1994年由Chen等从猪的小肠中分离纯化出的一种新的生物活性蛋白,其氨基酸序列与1995年由Utans等人在大鼠心脏移植排斥反应中克隆出的巨噬细胞因子Allograft Inflammatory Factor-1(同种异体移植炎症因子-1,AIF-1)高度同源(90%),两者属不同物种来源的同一蛋白质,故并称为Daintain/AIF-1。Daintain/AIF-1分子量17kD,主要由激活的巨噬细胞表达和分泌,是一种多功能的细胞因子,广泛参与炎症和免疫相关的多种疾病的发生发展过程,如血管病变、移植排斥、肿瘤以及自身免疫疾病等。
1型糖尿病糖尿病(Type 1 Diabetes Mellitum，T1DM)是一种T淋巴细胞介导的自身免疫疾病,以胰岛炎引发的胰岛β细胞的选择性破坏为特征。在发病前的胰岛炎阶段,活化的巨噬细胞、T淋巴细胞等大量浸润胰岛,释放出炎症介质如细胞因子和NO等协同作用,引起β细胞凋亡、坏死以及胰岛素分泌异常等功能损伤,进而发展为T1DM。目前T1DM发病的分子机理还未完全阐明,但大量研究表明炎症和免疫相关的细胞因子在这一进程中起着关键作用。我们的前期研究发现Daintain/AIF-1在正常胰腺组织中不表达,但在T1DM模型BB大鼠侵润胰腺的巨噬细胞中大量表达,表明炎症因子Daintain/AIF-1与T1DM的发病机理有关,但具体机制仍未明确。为了研究Daintain/AIF-1在T1DM发病中的作用,本论文主要开展了以下工作：
第一部分：以大鼠β细胞系INS-1为实验模型,在细胞水平上研究了Daintain/AIF-1对T1DM中p细胞功能异常的影响。在细胞培养基中添加不同浓度的Daintain/AIF-1刺激后,检测INS-1细胞活力、凋亡、周期、胰岛素分泌和NO产量的变化,结果发现：
1. Daintain/AIF-1对INS-1细胞具有毒性作用,能抑制细胞活力。
2. Daintain/AIF-1能够诱导INS-1细胞的凋亡,特别是早期凋亡。提示Daintain/AIF-1可能在凋亡的起始阶段起刺激性作用,最终导致INS-1细胞活力的降低。
3. Daintain/AIF-1不影响INS-1细胞的基础胰岛素分泌,但是抑制了20mM葡萄糖条件下的葡萄糖刺激的胰岛素分泌(GSIS)水平,说明Daintain/AIF-1损伤了INS-1细胞的葡萄糖反应性,这是Daintain/AIF-1对INS-1细胞毒性作用的另一个方面。
4. Daintain/AIF-1显著提升了INS-1细胞的NO产量,推测NO水平的上升可能和细胞凋亡的增加和GSIS的下降有关,可能是Daintain/AIF-1诱导的β细胞毒性作用的机制之一。
5. Daintain/AIF-1影响INS-1细胞周期,将细胞阻滞在G0/G1期,使得进入S期和G2/M期的细胞减少,以此来抑制细胞增殖,且Daintain/AIF-1浓度越大,作用越明显。
第二部分：寻找Daintain/AIF-1在胰腺中的相互作用蛋白,为深入了解Daintain/AIF-1对β细胞毒性作用机制提供思路。采用Clontech MatchmakerTM GAL4酵母双杂交系统3来进行人胰腺MatchmakerTM cDNA文库中Daintain/AIF-1相互作用蛋白基因的筛选,主要结果为：
1.构建了诱饵质粒pGBKT7-Daintain/AIF-1,经检测可以在AH109酵母中正确表达出诱饵融合蛋白BD-Daintain/AIF-1,对酵母细胞无毒性,且没有自激活性。
2.扩增了人胰腺cDNA文库,转化入AH 109/pGBKT7-Daintain/AIF-1酵母,涂布SD/-Trp/-Leu/-His/-Ade平板并进行β-半乳糖苷酶活性检测,初步筛选出64个Ade+His+lacZ+三阳性候选酵母克隆。
3.进行回转实验和一对一验证实验排除假阳性,结果仅获得1种文库质粒。对其cDNA插入片段测序后Blast比对并进行阅读框分析,发现该片段翻译时发生了移码,仅表达出一段32个氨基酸残基的未知小肽段,说明该质粒是假阳性。本次筛选未获得阳性结果,是酵母双杂交系统假阳性率非常高这一重大缺陷的一次实例。
综上,本研究首次发现Daintain/AIF-1对INS-1细胞具有毒性作用,Daintain/AIF-1可能通过将细胞阻滞在G0/G1期来抑制细胞增殖,以及上调NO产量来刺激细胞凋亡和损伤胰岛素分泌。这说明细胞因子Daintain/AIF-1促进了β细胞的功能异常,在TIDM的起始和发展中起重要的推动作用。
In 1994, a bioactive polypeptide—"Daintain" was isolated and characterized from porcine intestines by Chen et al. In 1995, Allograft inflammatory factor-1 (AIF-1) was cloned by Utans et al from activated macrophages of rat atherosclerotic allogenic heart grafts. Daintain and AIF-1 of pig, rat, and human origin are identical proteins with only species-specific amino acid differences. Hence, we call the polypeptide "Daintain/AIF-1". Daintain/AIF-1 is a 17kD cytokine that expressed mainly in macrophages and activated T cell. It is regarded as a novel multifunctional inflammatory factor that plays important roles in allograft rejection, vasculopathy, cancer, and autoimmune diseases.
Type 1 (Insulin-dependent) Diabetes Mellitum (T1DM) is characterized by a progressive autoimmune-mediated insulitis culminating in the death of pancreaticβcells. The (3 cell secretory dysfunction and apoptosis in the course of insulitis are perhaps caused by direct contact with activated T-cells and macrophages, and/or exposure to inflammatory mediators secreted by these cells, including cytokines and NO. We have previously observed a particularly dense accumulation of Daintain/AIF1-immunoreactive macrophages in the insulitis affecting the pancreatic islets of prediabetic BB rats, suggesting that Daintain/AIF-1 have a role in connection with the pathogenesis of T1D. In this study, we aimed to investigate further the role of Daintain/AIF-1 in the pathogenesis of T1DM. The following work has been done:
In the first part of the study, we explored the impact of Daintain/AIF-1 onβcell dysfunction in vitro using rat insulinoma INS-1 cells, a well-established insulin-secreting cell line for the study of diabetes. Various concentrations of Daintain/AIF-1 were added into the INS-1 culture medium. The influence of Daintain/AIF-1 on INS-1 cell viability, apoptosis, cell cycle, insulin secretion, and NO production were detected and the results are as follows:
1. Daintain/AIF-1 exerts toxic effects on INS-1 cells, as it suppresses INS-1 cell viability.
2. Daintain/AIF-1 is effective in inducing apoptosis in INS-1 cells, especially early apoptosis, suggesting that it plays stimulatory roles in the initial stages of apoptosis, leading to elimination of viable cells and subsequently a decrease in INS-1 cell viability.
3. Daintain/AIF-1 caused no significant alteration effects on the basic insulin secretion (BIS) of INS-1 cells, but reduced glucose-stimulated insulin secretion (GSIS) levels, implying an impairment role of Daintain/AIF-1 on insulin secretion of INS-1 cells responding to high glucose levels. Besides the aforementioned suppression on cell viability, this inhibition of glucose-responsiveness might be another toxic effect that Daintain/AIF-1 exerts on p cell dysfunction in T1DM.
4. NO production in INS-1 cells increased significantly under Daintain/AIF-1 treatment. This suggests that the increase in NO level may be contributive to the increased apoptosis and decreased GSIS, which may be one of the mechanisms of Daintain/AIF-1-inducedβcell toxicity
5. More cells were arrested in the G0/G1 phase after Daintain/AIF-1 treatment, makes the number of cells that proceed to S phase and G2/M phase decreased, demonstrating the inhibitor effect of Daintain/AIF-1 on INS-1 cell proliferation.
In the second part of the study, amied to identify some Daintain/AIF-1-interacting partners to better understanding the cytotoxic effects of Daintain/AIF-1 onβcells, we used Clontech MatchmakerTM GAL4 Two-Hybrid System 3 to perform a yeast two-hybrid screen of the human pancreas MatchmakerTM cDNA library. Here are the results:
1. We constructed the recombinant bait plasmid pGBKT7-Daintain/AIF-1. After transferred into yeast AH 109, the expressed fusion bait protein BD-Daintain/AIF-1 showed to be nontoxic to AH 109 yeast, and did not activate the reporter genes.
2. The amplified human pancreatic cDNA library was transferred into AH109/pGBKT7-Daintain/AIF-1 yeast and plated onto SD/-Trp/-Leu/-His/-Ade selective plates. After the (3-galactosidase activity assay we preliminarily screened out 64 Ade+His+lacZ+ candidate yeast clones.
3. Then we performed the "one-to-one" verification tests to exclude false positive results, and only one kind of library plasmid passed all the tests. The cDNA insert was sequenced and Blast in the Genebank. We analyzed the translation reading frame and found that a frameshift occurred, thus the fragment can only express an unknown 32-amino acid residues peptide. This result indicates that the plasmid is still a false positive. Although our experiments did not gain positive results, they exemplified the highly false positive rate of the yeast two-hybrid system, which is an inevitable major flaw.
In summary, this study provides the first description of the cytotoxic effects of Daintain/AIF-1 on INS-1βcells in vitro, as evidenced by decreased cell viability and GSIS, as well as upregulated apoptosis and NO production. We speculate that Daintain/AIF-1 may inhibit cell proliferation by arresting cells in G0/G1 phase, and induce cell apoptosis and suppress insulin secretion by stimulating NO production. Collectively, these data indicate that Daintain/AIF-1 exerts stimulatory effects inβcell dysfunction, thus may play important roles in the initiation and progress of T1DM.
1型糖尿病糖尿病(Type 1 Diabetes Mellitum，T1DM)是一种T淋巴细胞介导的自身免疫疾病,以胰岛炎引发的胰岛β细胞的选择性破坏为特征。在发病前的胰岛炎阶段,活化的巨噬细胞、T淋巴细胞等大量浸润胰岛,释放出炎症介质如细胞因子和NO等协同作用,引起β细胞凋亡、坏死以及胰岛素分泌异常等功能损伤,进而发展为T1DM。目前T1DM发病的分子机理还未完全阐明,但大量研究表明炎症和免疫相关的细胞因子在这一进程中起着关键作用。我们的前期研究发现Daintain/AIF-1在正常胰腺组织中不表达,但在T1DM模型BB大鼠侵润胰腺的巨噬细胞中大量表达,表明炎症因子Daintain/AIF-1与T1DM的发病机理有关,但具体机制仍未明确。为了研究Daintain/AIF-1在T1DM发病中的作用,本论文主要开展了以下工作：
第一部分：以大鼠β细胞系INS-1为实验模型,在细胞水平上研究了Daintain/AIF-1对T1DM中p细胞功能异常的影响。在细胞培养基中添加不同浓度的Daintain/AIF-1刺激后,检测INS-1细胞活力、凋亡、周期、胰岛素分泌和NO产量的变化,结果发现：
1. Daintain/AIF-1对INS-1细胞具有毒性作用,能抑制细胞活力。
2. Daintain/AIF-1能够诱导INS-1细胞的凋亡,特别是早期凋亡。提示Daintain/AIF-1可能在凋亡的起始阶段起刺激性作用,最终导致INS-1细胞活力的降低。
3. Daintain/AIF-1不影响INS-1细胞的基础胰岛素分泌,但是抑制了20mM葡萄糖条件下的葡萄糖刺激的胰岛素分泌(GSIS)水平,说明Daintain/AIF-1损伤了INS-1细胞的葡萄糖反应性,这是Daintain/AIF-1对INS-1细胞毒性作用的另一个方面。
4. Daintain/AIF-1显著提升了INS-1细胞的NO产量,推测NO水平的上升可能和细胞凋亡的增加和GSIS的下降有关,可能是Daintain/AIF-1诱导的β细胞毒性作用的机制之一。
5. Daintain/AIF-1影响INS-1细胞周期,将细胞阻滞在G0/G1期,使得进入S期和G2/M期的细胞减少,以此来抑制细胞增殖,且Daintain/AIF-1浓度越大,作用越明显。
第二部分：寻找Daintain/AIF-1在胰腺中的相互作用蛋白,为深入了解Daintain/AIF-1对β细胞毒性作用机制提供思路。采用Clontech MatchmakerTM GAL4酵母双杂交系统3来进行人胰腺MatchmakerTM cDNA文库中Daintain/AIF-1相互作用蛋白基因的筛选,主要结果为：
1.构建了诱饵质粒pGBKT7-Daintain/AIF-1,经检测可以在AH109酵母中正确表达出诱饵融合蛋白BD-Daintain/AIF-1,对酵母细胞无毒性,且没有自激活性。
2.扩增了人胰腺cDNA文库,转化入AH 109/pGBKT7-Daintain/AIF-1酵母,涂布SD/-Trp/-Leu/-His/-Ade平板并进行β-半乳糖苷酶活性检测,初步筛选出64个Ade+His+lacZ+三阳性候选酵母克隆。
3.进行回转实验和一对一验证实验排除假阳性,结果仅获得1种文库质粒。对其cDNA插入片段测序后Blast比对并进行阅读框分析,发现该片段翻译时发生了移码,仅表达出一段32个氨基酸残基的未知小肽段,说明该质粒是假阳性。本次筛选未获得阳性结果,是酵母双杂交系统假阳性率非常高这一重大缺陷的一次实例。
综上,本研究首次发现Daintain/AIF-1对INS-1细胞具有毒性作用,Daintain/AIF-1可能通过将细胞阻滞在G0/G1期来抑制细胞增殖,以及上调NO产量来刺激细胞凋亡和损伤胰岛素分泌。这说明细胞因子Daintain/AIF-1促进了β细胞的功能异常,在TIDM的起始和发展中起重要的推动作用。
In 1994, a bioactive polypeptide—"Daintain" was isolated and characterized from porcine intestines by Chen et al. In 1995, Allograft inflammatory factor-1 (AIF-1) was cloned by Utans et al from activated macrophages of rat atherosclerotic allogenic heart grafts. Daintain and AIF-1 of pig, rat, and human origin are identical proteins with only species-specific amino acid differences. Hence, we call the polypeptide "Daintain/AIF-1". Daintain/AIF-1 is a 17kD cytokine that expressed mainly in macrophages and activated T cell. It is regarded as a novel multifunctional inflammatory factor that plays important roles in allograft rejection, vasculopathy, cancer, and autoimmune diseases.
Type 1 (Insulin-dependent) Diabetes Mellitum (T1DM) is characterized by a progressive autoimmune-mediated insulitis culminating in the death of pancreaticβcells. The (3 cell secretory dysfunction and apoptosis in the course of insulitis are perhaps caused by direct contact with activated T-cells and macrophages, and/or exposure to inflammatory mediators secreted by these cells, including cytokines and NO. We have previously observed a particularly dense accumulation of Daintain/AIF1-immunoreactive macrophages in the insulitis affecting the pancreatic islets of prediabetic BB rats, suggesting that Daintain/AIF-1 have a role in connection with the pathogenesis of T1D. In this study, we aimed to investigate further the role of Daintain/AIF-1 in the pathogenesis of T1DM. The following work has been done:
In the first part of the study, we explored the impact of Daintain/AIF-1 onβcell dysfunction in vitro using rat insulinoma INS-1 cells, a well-established insulin-secreting cell line for the study of diabetes. Various concentrations of Daintain/AIF-1 were added into the INS-1 culture medium. The influence of Daintain/AIF-1 on INS-1 cell viability, apoptosis, cell cycle, insulin secretion, and NO production were detected and the results are as follows:
1. Daintain/AIF-1 exerts toxic effects on INS-1 cells, as it suppresses INS-1 cell viability.
2. Daintain/AIF-1 is effective in inducing apoptosis in INS-1 cells, especially early apoptosis, suggesting that it plays stimulatory roles in the initial stages of apoptosis, leading to elimination of viable cells and subsequently a decrease in INS-1 cell viability.
3. Daintain/AIF-1 caused no significant alteration effects on the basic insulin secretion (BIS) of INS-1 cells, but reduced glucose-stimulated insulin secretion (GSIS) levels, implying an impairment role of Daintain/AIF-1 on insulin secretion of INS-1 cells responding to high glucose levels. Besides the aforementioned suppression on cell viability, this inhibition of glucose-responsiveness might be another toxic effect that Daintain/AIF-1 exerts on p cell dysfunction in T1DM.
4. NO production in INS-1 cells increased significantly under Daintain/AIF-1 treatment. This suggests that the increase in NO level may be contributive to the increased apoptosis and decreased GSIS, which may be one of the mechanisms of Daintain/AIF-1-inducedβcell toxicity
5. More cells were arrested in the G0/G1 phase after Daintain/AIF-1 treatment, makes the number of cells that proceed to S phase and G2/M phase decreased, demonstrating the inhibitor effect of Daintain/AIF-1 on INS-1 cell proliferation.
In the second part of the study, amied to identify some Daintain/AIF-1-interacting partners to better understanding the cytotoxic effects of Daintain/AIF-1 onβcells, we used Clontech MatchmakerTM GAL4 Two-Hybrid System 3 to perform a yeast two-hybrid screen of the human pancreas MatchmakerTM cDNA library. Here are the results:
1. We constructed the recombinant bait plasmid pGBKT7-Daintain/AIF-1. After transferred into yeast AH 109, the expressed fusion bait protein BD-Daintain/AIF-1 showed to be nontoxic to AH 109 yeast, and did not activate the reporter genes.
2. The amplified human pancreatic cDNA library was transferred into AH109/pGBKT7-Daintain/AIF-1 yeast and plated onto SD/-Trp/-Leu/-His/-Ade selective plates. After the (3-galactosidase activity assay we preliminarily screened out 64 Ade+His+lacZ+ candidate yeast clones.
3. Then we performed the "one-to-one" verification tests to exclude false positive results, and only one kind of library plasmid passed all the tests. The cDNA insert was sequenced and Blast in the Genebank. We analyzed the translation reading frame and found that a frameshift occurred, thus the fragment can only express an unknown 32-amino acid residues peptide. This result indicates that the plasmid is still a false positive. Although our experiments did not gain positive results, they exemplified the highly false positive rate of the yeast two-hybrid system, which is an inevitable major flaw.
In summary, this study provides the first description of the cytotoxic effects of Daintain/AIF-1 on INS-1βcells in vitro, as evidenced by decreased cell viability and GSIS, as well as upregulated apoptosis and NO production. We speculate that Daintain/AIF-1 may inhibit cell proliferation by arresting cells in G0/G1 phase, and induce cell apoptosis and suppress insulin secretion by stimulating NO production. Collectively, these data indicate that Daintain/AIF-1 exerts stimulatory effects inβcell dysfunction, thus may play important roles in the initiation and progress of T1DM.
引文
[1]Chen ZW, Ostenson CG, Bergman T, et al. Purification and characterization of a novel porcine gut regulatory peptide, daintain, with effects on insulin release. Eur. J. Endocrinol,1994,130(Suppl 2):32.
[2]Utans U, Arceci RJ, Yamashita Y, et al. Cloning and characterization of allograft inflammatory factor-1:a novel macrophage factor Identified in Rat Cardiac Allografts with Chronic Rejection. J. Clin. Invest.,1995,95(6):2954-2962.
[3]Utans U, Quist WC, McManus BM, et al. Allograft inflammatory factory-1. A cytokine-responsive macrophage molecule expressed in transplanted human hearts. Transplantation,1996,61(9):1387-1392.
[4]Imai Y, Ibata I, Ito D, et al. A novel gene ibal in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun,1996,224(3):855-862.
[5]Tanaka S, Suzuki K, Watanabe M, et al. Upregulation of a new microglial gene, mrf-1, in response to programmed neuronal cell death and degeneration. J Neurosci,1998,18(16):6358-6369.
[6]Chen ZW, Ahren B, Ostenson CG, et al. Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats. Proc Natl Acad Sci U S A,1997,94(25): 13879-13884.
[7]Glover MD, Seidel GE, Jr. Increased messenger RNA for allograft inflammatory factor-1, LERK-5, and a novel gene in 17.5-day relative to 15.5-day bovine embryos. Biol Reprod,2003,69(3):1002-1012.
[8]Fujiki K, Shin DH, Nakao M, et al. Molecular cloning of carp (Cyprinus carpio) CC chemokine, CXC chemokine receptors, allograft inflammatory factor-1, and natural killer cell enhancing factor by use of suppression subtractive hybridization. Immunogenetics,1999,49(10):909-914.
[9]Muller WE, Krasko A, Skorokhod A, et al. Histocompatibility reaction in tissue and cells of the marine sponge Suberites domuncula in vitro and in vivo:central role of the allograft inflammatory factor 1. Immunogenetics,2002,54(1):48-58.
[10]Deininger MH, Meyermann R, Schluesener HJ. The allograft inflammatory factor-1 family of proteins. FEBS Lett,2002,514(2-3):115-121.
[11]Turner DM, Pravica V, Sinnott PJ, et al. Polymorphism in the promoter region of the gene encoding human allograft inflammatory factor-1. Eur J Immunogenet, 2001,28(4):449-450.
[12]Sibinga NE, Feinberg MW, Yang H, et al. Macrophage-restricted and interferon gamma-inducible expression of the allograft inflammatory factor-1 gene requires Pu.1. J Biol Chem,2002,277(18):16202-16210.
[13]Watano K, Iwabuchi K, Fujii S, et al. Allograft inflammatory factor-1 augments production of interleukin-6,-10 and -12 by a mouse macrophage line. Immunology,2001,104(3):307-316.
[14]Yang ZF, Ho DW, Lau CK, et al. Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages. Int Immunol,2005,17(11):1391-1397.
[15]Lee G, Xiang Z, Brannagan TH,3rd, et al. Differential gene expression in chronic inflammatory demyelinating polyneuropathy (CIDP) skin biopsies. J Neurol Sci,2009,290(1-2):115-122.
[16]Orsmark C, Skoog T, Jeskanen L, et al. Expression of allograft inflammatory factor-1 in inflammatory skin disorders. Acta Derm Venereol,2007,87(3): 223-227.
[17]Postler E, Rimner A, Beschorner R, et al. "Allograft-inflammatory-factor-1 is upregulated in microglial cells in human cerebral infarctions". J Neuroimmunol, 2000,108(1-2):244-250.
[18]Deininger MH, Weinschenk T, Meyermann R, et al. The allograft inflammatory factor-1 in Creutzfeldt-Jakob disease brains. Neuropathol Appl Neurobiol,2003, 29(4):389-399.
[19]Herden C, Schluesener HJ, Richt JA. Expression of allograft inflammatory factor-1 and haeme oxygenase-1 in brains of rats infected with the neurotropic Borna disease virus. Neuropathol Appl Neurobiol,2005,31(5):512-521.
[20]Schluesener HJ, Seid K, Kretzschmar J, et al. Allograft-inflammatory factor-1 in rat experimental autoimmune encephalomyelitis, neuritis, and uveitis: expression by activated macrophages and microglial cells. Glia,1998,24(2): 244-251.
[21]Schluesener HJ, Seid K, Meyermann R. Effects of autoantigen and dexamethasone treatment on expression of endothelial-monocyte activating polypeptide II and allograft-inflammatory factor-1 by activated macrophages and microglial cells in lesions of experimental autoimmune encephalomyelitis, neuritis and uveitis. Acta Neuropathol,1999,97(2):119-126.
[22]Morohashi T, Iwabuchi K, Watano K, et al. Allograft inflammatory factor-1 regulates trinitrobenzene sulphonic acid-induced colitis. Immunology,2003, 110(1):112-119.
[23]Tsubata Y, Sakatsume M, Ogawa A, et al. Expression of allograft inflammatory factor-1 in kidneys:A novel molecular component of podocyte. Kidney Int,2006, 70(11):1948-1954.
[24]Kimura M, Kawahito Y, Obayashi H, et al. A critical role for allograft inflammatory factor-1 in the pathogenesis of rheumatoid arthritis. J Immunol, 2007,178(5):3316-3322.
[25]Pawlik A, Kurzawski M, Szczepanik T, et al. Association of allograft inflammatory factor-1 gene polymorphism with rheumatoid arthritis. Tissue Antigens,2008,72(2):171-175.
[26]Autieri MV, Kelemen S, Thomas BA, et al. Allograft inflammatory factor-1 expression correlates with cardiac rejection and development of cardiac allograft vasculopathy. Circulation,2002,106(17):2218-2223.
[27]Kelemen SE, Autieri MV. Expression of allograft inflammatory factor-1 in T lymphocytes:a role in T-lymphocyte activation and proliferative arteriopathies. Am J Pathol,2005,167(2):619-626.
[28]Autieri MV, Carbone CM. Overexpression of allograft inflammatory factor-1 promotes proliferation of vascular smooth muscle cells by cell cycle deregulation. Arterioscler Thromb Vase Biol,2001,21(9):1421-1426.
[29]Chen X, Kelemen SE, Autieri MV. AIF-1 expression modulates proliferation of human vascular smooth muscle cells by autocrine expression of G-CSF. Arterioscler Thromb Vase Biol,2004,24(7):1217-1222.
[30]Autieri MV, Kelemen SE, Wendt KW. AIF-1 is an actin-polymerizing and Rac1-activating protein that promotes vascular smooth muscle cell migration. Circ Res,2003,92(10):1107-1114.
[31]Tian Y, Autieri MV. Cytokine expression and AIF-1-mediated activation of Rac2 in vascular smooth muscle cells:a role for Rac2 in VSMC activation. Am J Physiol Cell Physiol,2007,292(2):C841-849.
[32]Sommerville LJ, Kelemen SE, Autieri MV. Increased smooth muscle cell activation and neointima formation in response to injury in AIF-1 transgenic mice. Arterioscler Thromb Vasc Biol,2008,28(1):47-53.
[33]Sommerville LJ, Xing C, Kelemen SE, et al. Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity. Cardiovasc Res,2009,81(1):206-215.
[34]Broglio L, Erne B, Tolnay M, et al. Allograft inflammatory factor-1:a pathogenetic factor for vasculitic neuropathy. Muscle Nerve,2008,38(4): 1272-1279.
[35]Jiang W, Kong L, Wu X, et al. Allograft Inflammatory Factor-1 is Up-regulated in Warm and Cold Ischemia-Reperfusion Injury in Rat Liver and may be Inhibited by FK506. J Surg Res,2009,15(3):102-111.
[36]Tian Y, Jain S, Kelemen SE, et al. AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis. Am J Physiol Cell Physiol, 2009,296(2):C256-266.
[37]Tian Y, Kelemen SE, Autieri MV. Inhibition of AIF-1 expression by constitutive siRNA expression reduces macrophage migration, proliferation, and signal transduction initiated by atherogenic stimuli. Am J Physiol Cell Physiol,2006, 290(4):C1083-1091.
[38]Mishima T, Iwabuchi K, Fujii S, et al. Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/-mice. Int J Mol Med,2008,21(2):181-187.
[39]Autieri MV, Carbone CJ, Eisen H. The growth enhancing effects of allograft inflammatory Factor-1 (AIF-1) in VSMC are dose-dependent and mediated by its ability to bind calcium. J Heart Lung Transplant,2001,20(2):198.
[40]Autieri MV. The Role of Allograft Inflammatory Factor-1 in Development of Coronary Artery Vasculopathy. Drug News Perspect,2002,15(8):498-505.
[41]Raisanen-Sokolowski A, Glysing-Jensen T, Mottram PL, et al. Sustained anti-CD4/CD8 treatment blocks inflammatory activation and intimal thickening in mouse heart allografts. Arterioscler Thromb Vasc Biol,1997,17(10): 2115-2122.
[42]Grimm PC, McKenna R, Nickerson P, et al. Clinical rejection is distinguished from subclinical rejection by increased infiltration by a population of activated macrophages. J Am Soc Nephrol,1999,10(7):1582-1589.
[43]Nagakawa Y, Nomoto S, Kato Y, et al. Over-expression of AIF-1 in liver allografts and peripheral blood correlates with acute rejection after transplantation in rats. Am J Transplant,2004,4(12):1949-1957.
[44]Kruse M, Steffen R, Batel R, et al. Differential expression of allograft inflammatory factor 1 and of glutathione peroxidase during auto- and allograft response in marine sponges. J Cell Sci,1999,112 (Pt 23):4305-4313.
[45]Shimada S, Iwabuchi K, Watano K, et al. Expression of allograft inflammatory factor-1 in mouse uterus and poly(I:C)-induced fetal resorption. Am J Reprod Immunol,2003,50(1):104-112.
[46]Koshiba H, Kitawaki J, Teramoto M, et al. Expression of allograft inflammatory factor-1 in human eutopic endometrium and endometriosis:possible association with progression of endometriosis. J Clin Endocrinol Metab,2005,90(1): 529-537.
[47]Iida H, Doiguchi M, Yamashita H, et al. Spermatid-specific expression of Ibal, an ionized calcium binding adapter molecule-1, in rat testis. Biol Reprod,2001, 64(4):1138-1146.
[48]Kohler C. Allograft inflammatory factor-1/Ionized calcium-binding adapter molecule 1 is specifically expressed by most subpopulations of macrophages and spermatids in testis. Cell Tissue Res,2007,330(2):291-302.
[49]Eike MC, Olsson M, Undlien DE, et al. Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families. Genes Immun,2009,10(2):141-150.
[50]Del Galdo F, Artlett CM, Jimenez SA. The role of allograft inflammatory factor 1 in systemic sclerosis. Curr Opin Rheumatol,2006,18(6):588-593.
[51]Del Galdo F, Maul GG, Jimenez SA, et al. Expression of allograft inflammatory factor 1 in tissues from patients with systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor beta. Arthritis Rheum,2006,54(8):2616-2625.
[52]Del Galdo F, Jimenez SA. T cells expressing allograft inflammatory factor 1 display increased chemotaxis and induce a profibrotic phenotype in normal fibroblasts in vitro. Arthritis Rheum,2007,56(10):3478-3488.
[53]Deininger MH, Seid K, Engel S, et al. Allograft inflammatory factor-1 defines a distinct subset of infiltrating macrophages/microglial cells in rat and human gliomas. Acta Neuropathol,2000,100(6):673-680.
[54]Jia J, Cai Y, Wang R, et al. Overexpression of allograft inflammatory factor-1 promotes the proliferation and migration of human endothelial cells (HUV-EC-C) probably by up-regulation of bFGF. Pediatr Res,2010,67(1):29-34.
[55]Jia J, Bai Y, Fu K, et al. Expression of allograft inflammatory factor-1 and CD68 in haemangioma:implication in the progression of haemangioma. Br J Dermatol, 2008,159(4):811-819.
[56]Liu S, Tan WY, Chen QR, et al. Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF-kappaB/cyclin D1 pathway and facilitates tumor growth. Cancer Sci,2008,99(5):952-957.
[57]李发芳,马金梁,陈正望.应用原位杂交检测乳腺癌中大炎肽基因的表达.现代肿瘤医学,2008,16(2)：201-203.
[58]Mentschel J, Deininger MH, Schluesener HJ, et al. Effects of malnutrition on the expression of daintain/AIF-1 in the gut mucosa of pigs. J Vet Med A Physiol Pathol Clin Med,2002,49(4):184-188.
[59]Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol,2009,5(4):219-226.
[60]Yoon JW, Jun HS. Cellular and molecular pathogenic mechanisms of insulin-dependent diabetes mellitus. Ann N Y Acad Sci,2001,928(3):200-211.
[61]Mandrup-Poulsen T, Zumsteg U, Reimers J, et al. Involvement of interleukin 1 and interleukin 1 antagonist in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. Cytokine,1993,5(3):185-191.
[62]Donath MY, Boni-Schnetzler M, Ellingsgaard H, et al. Cytokine production by islets in health and diabetes:cellular origin, regulation and function. Trends Endocrinol Metab,2010,21(5):261-267.
[63]Ling Z, In't Veld PA, Pipeleers DG. Interaction of interleukin-1 with islet beta-cells. Distinction between indirect, aspecific cytotoxicity and direct, specific functional suppression. Diabetes,1993,42(1):56-65.
[64]Darville MI, Eizirik DL. Regulation by cytokines of the inducible nitric oxide synthase promoter in insulin-producing cells. Diabetologia,1998,41(9): 1101-1108.
[65]Yamada K, Takane-Gyotoku N, Yuan X, et al. Mouse islet cell lysis mediated by interleukin-1-induced Fas. Diabetologia,1996,39(11):1306-1312.
[66]Stassi G, Todaro M, Richiusa P, et al. Expression of apoptosis-inducing CD95 (Fas/Apo-1) on human beta-cells sorted by flow-cytometry and cultured in vitro. Transplant Proc,1995,27(6):3271-3275.
[67]Petrovsky N, Silva D, Socha L, et al. The role of Fas ligand in beta cell destruction in autoimmune diabetes of NOD mice. Ann N Y Acad Sci,2002, 958(4):204-208.
[68]Wachlin G, Augstein P, Schroder D, et al. IL-1beta, IFN-gamma and TNF-alpha increase vulnerability of pancreatic beta cells to autoimmune destruction. J Autoimmun,2003,20(4):303-312.
[69]Delaney CA, Green MH, Lowe JE, et al. Endogenous nitric oxide induced by interleukin-1 beta in rat islets of Langerhans and HIT-T15 cells causes significant DNA damage as measured by the 'comet' assay. FEBS Lett,1993, 333(3):291-295.
[70]Bolaffi JL, Rodd GG, Wang J, et al. Interrelationship of changes in islet nicotine adeninedinucleotide, insulin secretion, and cell viability induced by interleukin-1 beta. Endocrinology,1994,134(2):537-542.
[71]Mandrup-Poulsen T. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia,1996,39(9):1005-1029.
[72]Suk K, Kim S, Kim YH, et al. IFN-gamma/TNF-alpha synergism as the final effector in autoimmune diabetes:a key role for STAT1/IFN regulatory factor-1 pathway in pancreatic beta cell death. J Immunol,2001,166(7):4481-4489.
[73]Yang XD, Tisch R, Singer SM, et al. Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. Journal of Experimental Medicine, 1994,180(3):995-1004.
[74]Green EA, Flavell RA. Tumor necrosis factor-alpha and the progression of diabetes in non-obese diabetic mice. Immunol Rev,1999,169(3):11-22.
[75]Christen U, Wolfe T, Mohrle U, et al. A dual role for TNF-alpha in type 1 diabetes:islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis. J Immunol,2001,166(12): 7023-7032.
[76]Lee LF, Xu B, Michie SA, et al. The role of TNF-alpha in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse:analysis of dendritic cell maturation. Proc Natl Acad Sci U S A,2005,102(44):15995-16000.
[77]Richardson SJ, Willcox A, Bone AJ, et al. Immunopathology of the human pancreas in type-I diabetes. Semin Immunopathol,2011,33(1):9-21.
[78]Ban L, Zhang J, Wang L, et al. Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism. Proc Natl Acad Sci U S A,2008, 105(36):13644-13649.
[79]Foulis AK, McGill M, Farquharson MA. Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol,1991,165(2):97-103.
[80]Rabinovitch A, Suarez-Pinzon WL, Sorensen O, et al. IFN-gamma gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice. J Immunol,1995,154(9): 4874-4882.
[81]Muir A, Peck A, Clare-Salzler M, et al. Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. J Clin Invest,1995,95(2):628-634.
[82]Sarvetnick N, Shizuru J, Liggitt D, et al. Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma. Nature,1990,346(6287): 844-847.
[83]Debray-Sachs M, Carnaud C, Boitard C, et al. Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma. J Autoimmun,1991,4(2): 237-248.
[84]Nicoletti F, Meroni PL, Landolfo S, et al. Prevention of diabetes in BB/Wor rats treated with monoclonal antibodies to interferon-gamma. Lancet,1990, 336(8710):319.
[85]Campbell IL, Iscaro A, Harrison LC. IFN-gamma and tumor necrosis factor-alpha. Cytotoxicity to murine islets of Langerhans. J Immunol,1988, 141(7):2325-2329.
[86]Chang I, Cho N, Kim S, et al. Role of calcium in pancreatic islet cell death by IFN-gamma/TNF-alpha. J Immunol,2004,172(11):7008-7014.
[87]Hultgren B, Huang X, Dybdal N, et al. Genetic absence of gamma-interferon delays but does not prevent diabetes in NOD mice. Diabetes,1996,45(6): 812-817.
[88]Savinov AY, Wong FS, Chervonsky AV. IFN-gamma affects homing of diabetogenic T cells. J Immunol,2001,167(11):6637-6643.
[89]Amrani A, Verdaguer J, Thiessen S, et al. IL-1 alpha, IL-1beta, and IFN-gamma mark beta cells for Fas-dependent destruction by diabetogenic CD4+ T lymphocytes. J Clin Invest,2000,105(4):459-468.
[90]Thomas HE, Parker JL, Schreiber RD, et al. IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes. J Clin Invest,1998, 102(6):1249-1257.
[91]Sobel DO, Han J, Williams J, et al. Gamma interferon paradoxically inhibits the development of diabetes in the NOD mouse. J Autoimmun,2002,19(3): 129-137.
[92]Wang B, Andre I, Gonzalez A, et al. Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes. Proc Natl Acad Sci U S A, 1997,94(25):13844-13849.
[93]Serreze DV, Post CM, Chapman HD, et al. Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice. Diabetes,2000,49(12):2007-2011.
[94]Foulis AK, Farquharson MA, Meager A. Immunoreactive alpha-interferon in insulin-secreting beta cells in type 1 diabetes mellitus. Lancet,1987,2(8573): 1423-1427.
[95]Huang X, Yuang J, Goddard A, et al. Interferon expression in the pancreases of patients with type I diabetes. Diabetes,1995,44(6):658-664.
[96]Huang X, Hultgren B, Dybdal N, et al. Islet expression of interferon-alpha precedes diabetes in both the BB rat and streptozotocin-treated mice. Immunity, 1994,1(6):469-478.
[97]Stewart TA, Hultgren B, Huang X, et al. Induction of type I diabetes by interferon-alpha in transgenic mice. Science,1993,260(5116):1942-1946.
[98]Nakazawa T, Satoh J, Takahashi K, et al. Complete suppression of insulitis and diabetes in NOD mice lacking interferon regulatory factor-1. J Autoimmun, 2001,17(2):119-125.
[99]Devendra D, Eisenbarth GS. Interferon alpha--a potential link in the pathogenesis of viral-induced type 1 diabetes and autoimmunity. Clin Immunol, 2004,111(3):225-233.
[100]Devendra D, Jasinski J, Melanitou E, et al. Interferon-alpha as a mediator of polyinosinic:polycytidylic acid-induced type 1 diabetes. Diabetes,2005,54(9): 2549-2556.
[101]Peng RH, Paek E, Xia CQ, et al. Heightened interferon-alpha/beta response causes myeloid cell dysfunction and promotes T1D pathogenesis in NOD mice. Ann N Y Acad Sci,2006,1079(7):99-102.
[102]Li Q, Xu B, Michie SA, et al. Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A,2008,105(34): 12439-12444.
[103]Stewart TA. Neutralizing interferon alpha as a therapeutic approach to autoimmune diseases. Cytokine Growth Factor Rev,2003,14(2):139-154.
[104]Sobel DO, Ahvazi B. Alpha-interferon inhibits the development of diabetes in NOD mice. Diabetes,1998,47(12):1867-1872.
[105]Tanaka-Kataoka M, Kunikata T, Takayama S, et al. Oral use of interferon-alpha delays the onset of insulin-dependent diabetes mellitus in nonobese diabetes mice. J Interferon Cytokine Res,1999,19(8):877-879.
[106]Brod SA. Ingested type I interferon:a potential treatment for autoimmunity. J Interferon Cytokine Res,2002,22(12):1153-1166.
[107]Harris PE, Malanga D, Liu Z, et al. Effect of interferon alpha on MHC class II gene expression in ex vivo human islet tissue. Biochim Biophys Acta,2006, 1762(6):627-635.
[108]Allison J, Oxbrow L, Miller JF. Consequences of in situ production of IL-2 for islet cell death.Int Immunol,1994,6(4):541-549.
[109]Pacheco-Silva A, Bastos MG, Muggia RA, et al. Interleukin 2 receptor targeted fusion toxin (DAB486-IL-2) treatment blocks diabetogenic autoimmunity in non-obese diabetic mice. Eur J Immunol,1992,22(3):697-702.
[110]Molano RD, Pileggi A, Berney T, et al. Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody. Transplantation,2003,75(11):1812-1819.
[111]Serreze DV, Hamaguchi K, Leiter EH. Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmun,1989,2(6):759-776.
[112]Zielasek J, Burkart V, Naylor P, et al. Interleukin-2-dependent control of disease development in spontaneously diabetic BB rats. Immunology,1990,69(2): 209-214.
[113]Shi FD, Flodstrom M, Balasa B, et al. Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. Proc Natl Acad Sci U S A,2001, 98(12):6777-6782.
[114]D'Cruz LM, Klein L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol,2005,6(11):1152-1159.
[115]Yamanouchi J, Rainbow D, Serra P, et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet,2007,39(3): 329-337.
[116]Tang Q, Adams JY, Penaranda C, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity,2008, 28(5):687-697.
[117]McDaniel ML, Corbett JA, Kwon G, et al. A role for nitric oxide and other inflammatory mediators in cytokine-induced pancreatic beta-cell dysfunction and destruction. Advances in Experimental Medicine & Biology,1997, 426(5):313-319.
[118]Pitocco D, Zaccardi F, Di Stasio E, et al. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud,2010,7(1):15-25.
[119]Rabinovitch A, Suarez-Pinzon WL. Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus. Biochem Pharmacol,1998,55(8):1139-1149.
[120]Fields S, Song O. A novel genetic system to detect protein-protein interactions. Nature,1989,340(6230):245-246.
[121]Koegl M, Uetz P. Improving yeast two-hybrid screening systems. Brief Funct Genomic Proteomic,2007,6(4):302-312.
[122]Li JJ, Herskowitz I. Isolation of ORC6, a component of the yeast origin recognition complex by a one-hybrid system. Science,1993,262(5141): 1870-1874.
[123]SenGupta DJ, Zhang B, Kraemer B, et al. A three-hybrid system to detect RNA-protein interactions in vivo. Proc Natl Acad Sci U S A,1996,93(16): 8496-8501.
[124]Vidal M, Brachmann RK, Fattaey A, et al. Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions. Proc Natl Acad Sci U S A,1996,93(19):10315-10320.
[125]Bennett MA, Shern JF, Kahn RA. Reverse two-hybrid techniques in the yeast Saccharomyces cerevisiae. Methods Mol Biol,2004,261 (2):313-326.
[126]Serebriiskii I, Khazak V, Golemis EA. A two-hybrid dual bait system to discriminate specificity of protein interactions. J Biol Chem,1999,274(24): 17080-17087.
[127]Serebriiskii IG, Kotova E. Analysis of protein-protein interactions utilizing dual bait yeast two-hybrid system. Methods Mol Biol,2004,261 (7):263-296.
[128]Aronheim A. Improved efficiency sos recruitment system:expression of the mammalian GAP reduces isolation of Ras GTPase false positives. Nucleic Acids Res,1997,25(16):3373-3374.
[129]Johnsson N, Varshavsky A. Split ubiquitin as a sensor of protein interactions in vivo. Proc Natl Acad Sci U S A,1994,91(22):10340-10344.
[130]Schonhofer-Merl S, Torres-Ruiz RA. The Sos-recruitment system as a tool to analyze cellular localization of plant proteins:membrane localization of Arabidopsis thaliana PEPINO/PASTICCINO2. Mol Genet Genomics,2010, 283(5):439-449.
[131]Huang W, Wang SL, Lozano G, et al. cDNA library screening using the SOS recruitment system. Biotechniques,2001,30(1):94-98,100.
[132]Snider J, Kittanakom S, Curak J, et al. Split-ubiquitin based membrane yeast two-hybrid (MYTH) system:a powerful tool for identifying protein-protein interactions. J Vis Exp,2010,36(6):112-115
[133]Wehr MC, Laage R, Bolz U, et al. Monitoring regulated protein-protein interactions using split TEV. Nat Methods,2006,3(12):985-993.
[134]Luo Y, Batalao A, Zhou H, et al. Mammalian two-hybrid system:a complementary approach to the yeast two-hybrid system. Biotechniques,1997, 22(2):350-352.
[135]Lee JW, Lee SK. Mammalian two-hybrid assay for detecting protein-protein interactions in vivo. Methods Mol Biol,2004,261(7):327-336.
[136]Shui X, Lu X, Gao Y, et al. A mammalian two-hybrid system-based assay for small-molecular HIV fusion inhibitors targeting gp41. Antiviral Res,2011,90(1): 54-63.
[137]Karimova G, Pidoux J, Ullmann A, et al. A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A,1998, 95(10):5752-5756.
[138]Battesti A, Bouveret E. Improvement of bacterial two-hybrid vectors for detection of fusion proteins and transfer to pBAD-tandem affinity purification, calmodulin binding peptide, or 6-histidine tag vectors. Proteomics,2008,8(22): 4768-4771.
[139]Engelender S, Kaminsky Z, Guo X, et al. Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nat Genet, 1999,22(1):110-114.
[140]Soehn AS, Franck T, Biskup S, et al. Periphilin is a novel interactor of synphilin-1, a protein implicated in Parkinson's disease. Neurogenetics,2010, 11(2):203-215.
[141]Park UH, Kim EJ, Um SJ. A novel cytoplasmic adaptor for retinoic acid receptor (RAR) and thyroid receptor functions as a Derepressor of RAR in the absence of retinoic acid. J Biol Chem,2010,285(44):34269-34278.
[142]Moerdyk-Schauwecker M, Destephanis D, Hastie E, et al. Detecting protein-protein interactions in vesicular stomatitis virus using a cytoplasmic yeast two hybrid system. J Virol Methods,2011,173(2):203-212.
[143]Shi YH, Chen J, Li CH, et al. The establishment of a library screening method based on yeast two-hybrid system and its use to determine the potential interactions of liver proteins in ayu, Plecoglossus altivelis. Fish Shellfish Immunol,2011,30(4-5):1184-1187.
[144]Ito T, Chiba T, Ozawa R, et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci U S A,2001,98(8): 4569-4574.
[145]Parrish JR, Yu J, Liu G, et al. A proteome-wide protein interaction map for Campylobacter jejuni. Genome Biol,2007,8(7):R130.
[146]Hackbusch J, Richter K, Muller J, et al. A central role of Arabidopsis thaliana ovate family proteins in networking and subcellular localization of 3-aa loop extension homeodomain proteins. Proc Natl Acad Sci U S A,2005,102(13): 4908-4912.
[147]Formstecher E, Aresta S, Collura V, et al. Protein interaction mapping:a Drosophila case study. Genome Res,2005,15(3):376-384.
[148]Li S, Armstrong CM, Bertin N, et al. A map of the interactome network of the metazoan C. elegans. Science,2004,303(5657):540-543.
[149]Uetz P, Dong YA, Zeretzke C, et al. Herpesviral protein networks and their interaction with the human proteome. Science,2006,311(5758):239-242.
[150]Johansson M, Brooks AJ, Jans DA, et al. A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importin-beta and the viral helicase, NS3. J Gen Virol,2001,82(Pt 4):735-745.
[151]Vasudevan SG, Johansson M, Brooks AJ, et al. Characterisation of inter-and intra-molecular interactions of the dengue virus RNA dependent RNA polymerase as potential drug targets. Farmaco,2001,56(1-2):33-36.
[152]Bartel P, Chien CT, Sternglanz R, et al. Elimination of false positives that arise in using the two-hybrid system. Biotechniques,1993,14(6):920-924.
[153]von Mering C, Krause R, Snel B, et al. Comparative assessment of large-scale data sets of protein-protein interactions. Nature,2002,417(6887):399-403.
[154]Ratushny V, Golemis E. Resolving the network of cell signaling pathways using the evolving yeast two-hybrid system. Biotechniques,2008,44(5):655-662.
[155]Rajagopala SV, Titz B, Goll J, et al. The protein network of bacterial motility. Mol Syst Biol,2007,3(2):128.
[156]Fashena SJ, Serebriiskii I, Golemis EA. The continued evolution of two-hybrid screening approaches in yeast:how to outwit different preys with different baits. Gene,2000,250(1-2):1-14.
[157]Vidalain PO, Boxem M, Ge H, et al. Increasing specificity in high-throughput yeast two-hybrid experiments. Methods,2004,32(4):363-370.
[158]Stellberger T, Hauser R, Baiker A, et al. Improving the yeast two-hybrid system with permutated fusions proteins:the Varicella Zoster Virus interactome. Proteome Sci,2010,8(1):8.
[159]Chen YC, Rajagopala SV, Stellberger T, et al. Exhaustive benchmarking of the yeast two-hybrid system. Nat Methods,2010,7(9):667-668;author reply 668.
[160]Wang W, Huang B, Feng ZG, et al. Expression, purification, and characterization of functional recombinant human daintain/AIF-1 in Escherichia coli. Z Naturforsch C,2010,65(11-12):726-732.
[161]赵燕英.Daintain/AIF-1在1型糖尿病发生中的作用：[博士学位论文].保存地点：华中科技大学图书馆,2009
[162]James P, Halladay J, Craig EA. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics,1996,144(4): 1425-1436.
[163]Fu K, Zhao YY, Tang WX, et al. Preparation and identification of monoclonal antibodies against daintain. Hybridoma (Larchmt),2006,25(2):95-97.
[164]付康,程首超,刘收等.人同种异体移植炎症因子-1的基因克隆及其在小鼠成纤维细胞中的表达.华中科技大学学报(医学版),2007,36(5)：663-666.
[165]Yoon JW, Jun HS. Autoimmune destruction of pancreatic beta cells. Am J Ther, 2005,12(6):580-591.
[166]Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods,1983, 65(1-2):55-63.
[167]Green LC, Wagner DA, Glogowski J, et al. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem,1982,126(1):131-138.
[168]Lee BW, Kwon SJ, Chae HY, et al. Dose-related cytoprotective effect of alpha-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells. Free Radic Res,2009,43(1):68-77.
[169]Kolb H, Kolb-Bachofen V. Type 1 (insulin-dependent) diabetes mellitus and nitric oxide. Diabetologia,1992,35(8):796-797.
[170]Eizirik DL, Pavlovic D. Is there a role for nitric oxide in beta-cell dysfunction and damage in IDDM? Diabetes Metab Rev,1997,13(4):293-307.
[171]Hamid M, McCluskey JT, McClenaghan NH, et al. Comparison of the secretory properties of four insulin-secreting cell lines. Endocrine Research,2002,28(1-2): 35-47.
[172]Asfari M, Janjic D, Meda P, et al. Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. Endocrinology,1992,130(1):167-178.
[173]Skelin M, Rupnik M, Cencic A. Pancreatic beta cell lines and their applications in diabetes mellitus research. ALTEX,2010,27(2):105-113.
[174]Thomas HE, Darwiche R, Corbett JA, et al. Interleukin-1 plus gamma-interferon-induced pancreatic beta-cell dysfunction is mediated by beta-cell nitric oxide production. Diabetes,2002,51(2):311-316.
[175]Autieri MV. cDNA cloning of human allograft inflammatory factor-1:tissue distribution, cytokine induction, and mRNA expression in injured rat carotid arteries. Biochem Biophys Res Commun,1996,228(1):29-37.
[176]Autieri MV, Chen X. The ability of AIF-1 to activate human vascular smooth muscle cells is lost by mutations in the EF-hand calcium-binding region. Exp Cell Res,2005,307(1):204-211.
[177]Henquin JC. Regulation of insulin secretion:a matter of phase control and amplitude modulation. Diabetologia,2009,52(5):739-751.
[178]Janjic D, Asfari M. Effects of cytokines on rat insulinoma INS-1 cells. J Endocrinol,1992,132(1):67-76.
[2]Utans U, Arceci RJ, Yamashita Y, et al. Cloning and characterization of allograft inflammatory factor-1:a novel macrophage factor Identified in Rat Cardiac Allografts with Chronic Rejection. J. Clin. Invest.,1995,95(6):2954-2962.
[3]Utans U, Quist WC, McManus BM, et al. Allograft inflammatory factory-1. A cytokine-responsive macrophage molecule expressed in transplanted human hearts. Transplantation,1996,61(9):1387-1392.
[4]Imai Y, Ibata I, Ito D, et al. A novel gene ibal in the major histocompatibility complex class III region encoding an EF hand protein expressed in a monocytic lineage. Biochem Biophys Res Commun,1996,224(3):855-862.
[5]Tanaka S, Suzuki K, Watanabe M, et al. Upregulation of a new microglial gene, mrf-1, in response to programmed neuronal cell death and degeneration. J Neurosci,1998,18(16):6358-6369.
[6]Chen ZW, Ahren B, Ostenson CG, et al. Identification, isolation, and characterization of daintain (allograft inflammatory factor 1), a macrophage polypeptide with effects on insulin secretion and abundantly present in the pancreas of prediabetic BB rats. Proc Natl Acad Sci U S A,1997,94(25): 13879-13884.
[7]Glover MD, Seidel GE, Jr. Increased messenger RNA for allograft inflammatory factor-1, LERK-5, and a novel gene in 17.5-day relative to 15.5-day bovine embryos. Biol Reprod,2003,69(3):1002-1012.
[8]Fujiki K, Shin DH, Nakao M, et al. Molecular cloning of carp (Cyprinus carpio) CC chemokine, CXC chemokine receptors, allograft inflammatory factor-1, and natural killer cell enhancing factor by use of suppression subtractive hybridization. Immunogenetics,1999,49(10):909-914.
[9]Muller WE, Krasko A, Skorokhod A, et al. Histocompatibility reaction in tissue and cells of the marine sponge Suberites domuncula in vitro and in vivo:central role of the allograft inflammatory factor 1. Immunogenetics,2002,54(1):48-58.
[10]Deininger MH, Meyermann R, Schluesener HJ. The allograft inflammatory factor-1 family of proteins. FEBS Lett,2002,514(2-3):115-121.
[11]Turner DM, Pravica V, Sinnott PJ, et al. Polymorphism in the promoter region of the gene encoding human allograft inflammatory factor-1. Eur J Immunogenet, 2001,28(4):449-450.
[12]Sibinga NE, Feinberg MW, Yang H, et al. Macrophage-restricted and interferon gamma-inducible expression of the allograft inflammatory factor-1 gene requires Pu.1. J Biol Chem,2002,277(18):16202-16210.
[13]Watano K, Iwabuchi K, Fujii S, et al. Allograft inflammatory factor-1 augments production of interleukin-6,-10 and -12 by a mouse macrophage line. Immunology,2001,104(3):307-316.
[14]Yang ZF, Ho DW, Lau CK, et al. Allograft inflammatory factor-1 (AIF-1) is crucial for the survival and pro-inflammatory activity of macrophages. Int Immunol,2005,17(11):1391-1397.
[15]Lee G, Xiang Z, Brannagan TH,3rd, et al. Differential gene expression in chronic inflammatory demyelinating polyneuropathy (CIDP) skin biopsies. J Neurol Sci,2009,290(1-2):115-122.
[16]Orsmark C, Skoog T, Jeskanen L, et al. Expression of allograft inflammatory factor-1 in inflammatory skin disorders. Acta Derm Venereol,2007,87(3): 223-227.
[17]Postler E, Rimner A, Beschorner R, et al. "Allograft-inflammatory-factor-1 is upregulated in microglial cells in human cerebral infarctions". J Neuroimmunol, 2000,108(1-2):244-250.
[18]Deininger MH, Weinschenk T, Meyermann R, et al. The allograft inflammatory factor-1 in Creutzfeldt-Jakob disease brains. Neuropathol Appl Neurobiol,2003, 29(4):389-399.
[19]Herden C, Schluesener HJ, Richt JA. Expression of allograft inflammatory factor-1 and haeme oxygenase-1 in brains of rats infected with the neurotropic Borna disease virus. Neuropathol Appl Neurobiol,2005,31(5):512-521.
[20]Schluesener HJ, Seid K, Kretzschmar J, et al. Allograft-inflammatory factor-1 in rat experimental autoimmune encephalomyelitis, neuritis, and uveitis: expression by activated macrophages and microglial cells. Glia,1998,24(2): 244-251.
[21]Schluesener HJ, Seid K, Meyermann R. Effects of autoantigen and dexamethasone treatment on expression of endothelial-monocyte activating polypeptide II and allograft-inflammatory factor-1 by activated macrophages and microglial cells in lesions of experimental autoimmune encephalomyelitis, neuritis and uveitis. Acta Neuropathol,1999,97(2):119-126.
[22]Morohashi T, Iwabuchi K, Watano K, et al. Allograft inflammatory factor-1 regulates trinitrobenzene sulphonic acid-induced colitis. Immunology,2003, 110(1):112-119.
[23]Tsubata Y, Sakatsume M, Ogawa A, et al. Expression of allograft inflammatory factor-1 in kidneys:A novel molecular component of podocyte. Kidney Int,2006, 70(11):1948-1954.
[24]Kimura M, Kawahito Y, Obayashi H, et al. A critical role for allograft inflammatory factor-1 in the pathogenesis of rheumatoid arthritis. J Immunol, 2007,178(5):3316-3322.
[25]Pawlik A, Kurzawski M, Szczepanik T, et al. Association of allograft inflammatory factor-1 gene polymorphism with rheumatoid arthritis. Tissue Antigens,2008,72(2):171-175.
[26]Autieri MV, Kelemen S, Thomas BA, et al. Allograft inflammatory factor-1 expression correlates with cardiac rejection and development of cardiac allograft vasculopathy. Circulation,2002,106(17):2218-2223.
[27]Kelemen SE, Autieri MV. Expression of allograft inflammatory factor-1 in T lymphocytes:a role in T-lymphocyte activation and proliferative arteriopathies. Am J Pathol,2005,167(2):619-626.
[28]Autieri MV, Carbone CM. Overexpression of allograft inflammatory factor-1 promotes proliferation of vascular smooth muscle cells by cell cycle deregulation. Arterioscler Thromb Vase Biol,2001,21(9):1421-1426.
[29]Chen X, Kelemen SE, Autieri MV. AIF-1 expression modulates proliferation of human vascular smooth muscle cells by autocrine expression of G-CSF. Arterioscler Thromb Vase Biol,2004,24(7):1217-1222.
[30]Autieri MV, Kelemen SE, Wendt KW. AIF-1 is an actin-polymerizing and Rac1-activating protein that promotes vascular smooth muscle cell migration. Circ Res,2003,92(10):1107-1114.
[31]Tian Y, Autieri MV. Cytokine expression and AIF-1-mediated activation of Rac2 in vascular smooth muscle cells:a role for Rac2 in VSMC activation. Am J Physiol Cell Physiol,2007,292(2):C841-849.
[32]Sommerville LJ, Kelemen SE, Autieri MV. Increased smooth muscle cell activation and neointima formation in response to injury in AIF-1 transgenic mice. Arterioscler Thromb Vasc Biol,2008,28(1):47-53.
[33]Sommerville LJ, Xing C, Kelemen SE, et al. Inhibition of allograft inflammatory factor-1 expression reduces development of neointimal hyperplasia and p38 kinase activity. Cardiovasc Res,2009,81(1):206-215.
[34]Broglio L, Erne B, Tolnay M, et al. Allograft inflammatory factor-1:a pathogenetic factor for vasculitic neuropathy. Muscle Nerve,2008,38(4): 1272-1279.
[35]Jiang W, Kong L, Wu X, et al. Allograft Inflammatory Factor-1 is Up-regulated in Warm and Cold Ischemia-Reperfusion Injury in Rat Liver and may be Inhibited by FK506. J Surg Res,2009,15(3):102-111.
[36]Tian Y, Jain S, Kelemen SE, et al. AIF-1 expression regulates endothelial cell activation, signal transduction, and vasculogenesis. Am J Physiol Cell Physiol, 2009,296(2):C256-266.
[37]Tian Y, Kelemen SE, Autieri MV. Inhibition of AIF-1 expression by constitutive siRNA expression reduces macrophage migration, proliferation, and signal transduction initiated by atherogenic stimuli. Am J Physiol Cell Physiol,2006, 290(4):C1083-1091.
[38]Mishima T, Iwabuchi K, Fujii S, et al. Allograft inflammatory factor-1 augments macrophage phagocytotic activity and accelerates the progression of atherosclerosis in ApoE-/-mice. Int J Mol Med,2008,21(2):181-187.
[39]Autieri MV, Carbone CJ, Eisen H. The growth enhancing effects of allograft inflammatory Factor-1 (AIF-1) in VSMC are dose-dependent and mediated by its ability to bind calcium. J Heart Lung Transplant,2001,20(2):198.
[40]Autieri MV. The Role of Allograft Inflammatory Factor-1 in Development of Coronary Artery Vasculopathy. Drug News Perspect,2002,15(8):498-505.
[41]Raisanen-Sokolowski A, Glysing-Jensen T, Mottram PL, et al. Sustained anti-CD4/CD8 treatment blocks inflammatory activation and intimal thickening in mouse heart allografts. Arterioscler Thromb Vasc Biol,1997,17(10): 2115-2122.
[42]Grimm PC, McKenna R, Nickerson P, et al. Clinical rejection is distinguished from subclinical rejection by increased infiltration by a population of activated macrophages. J Am Soc Nephrol,1999,10(7):1582-1589.
[43]Nagakawa Y, Nomoto S, Kato Y, et al. Over-expression of AIF-1 in liver allografts and peripheral blood correlates with acute rejection after transplantation in rats. Am J Transplant,2004,4(12):1949-1957.
[44]Kruse M, Steffen R, Batel R, et al. Differential expression of allograft inflammatory factor 1 and of glutathione peroxidase during auto- and allograft response in marine sponges. J Cell Sci,1999,112 (Pt 23):4305-4313.
[45]Shimada S, Iwabuchi K, Watano K, et al. Expression of allograft inflammatory factor-1 in mouse uterus and poly(I:C)-induced fetal resorption. Am J Reprod Immunol,2003,50(1):104-112.
[46]Koshiba H, Kitawaki J, Teramoto M, et al. Expression of allograft inflammatory factor-1 in human eutopic endometrium and endometriosis:possible association with progression of endometriosis. J Clin Endocrinol Metab,2005,90(1): 529-537.
[47]Iida H, Doiguchi M, Yamashita H, et al. Spermatid-specific expression of Ibal, an ionized calcium binding adapter molecule-1, in rat testis. Biol Reprod,2001, 64(4):1138-1146.
[48]Kohler C. Allograft inflammatory factor-1/Ionized calcium-binding adapter molecule 1 is specifically expressed by most subpopulations of macrophages and spermatids in testis. Cell Tissue Res,2007,330(2):291-302.
[49]Eike MC, Olsson M, Undlien DE, et al. Genetic variants of the HLA-A, HLA-B and AIF1 loci show independent associations with type 1 diabetes in Norwegian families. Genes Immun,2009,10(2):141-150.
[50]Del Galdo F, Artlett CM, Jimenez SA. The role of allograft inflammatory factor 1 in systemic sclerosis. Curr Opin Rheumatol,2006,18(6):588-593.
[51]Del Galdo F, Maul GG, Jimenez SA, et al. Expression of allograft inflammatory factor 1 in tissues from patients with systemic sclerosis and in vitro differential expression of its isoforms in response to transforming growth factor beta. Arthritis Rheum,2006,54(8):2616-2625.
[52]Del Galdo F, Jimenez SA. T cells expressing allograft inflammatory factor 1 display increased chemotaxis and induce a profibrotic phenotype in normal fibroblasts in vitro. Arthritis Rheum,2007,56(10):3478-3488.
[53]Deininger MH, Seid K, Engel S, et al. Allograft inflammatory factor-1 defines a distinct subset of infiltrating macrophages/microglial cells in rat and human gliomas. Acta Neuropathol,2000,100(6):673-680.
[54]Jia J, Cai Y, Wang R, et al. Overexpression of allograft inflammatory factor-1 promotes the proliferation and migration of human endothelial cells (HUV-EC-C) probably by up-regulation of bFGF. Pediatr Res,2010,67(1):29-34.
[55]Jia J, Bai Y, Fu K, et al. Expression of allograft inflammatory factor-1 and CD68 in haemangioma:implication in the progression of haemangioma. Br J Dermatol, 2008,159(4):811-819.
[56]Liu S, Tan WY, Chen QR, et al. Daintain/AIF-1 promotes breast cancer proliferation via activation of the NF-kappaB/cyclin D1 pathway and facilitates tumor growth. Cancer Sci,2008,99(5):952-957.
[57]李发芳,马金梁,陈正望.应用原位杂交检测乳腺癌中大炎肽基因的表达.现代肿瘤医学,2008,16(2)：201-203.
[58]Mentschel J, Deininger MH, Schluesener HJ, et al. Effects of malnutrition on the expression of daintain/AIF-1 in the gut mucosa of pigs. J Vet Med A Physiol Pathol Clin Med,2002,49(4):184-188.
[59]Eizirik DL, Colli ML, Ortis F. The role of inflammation in insulitis and beta-cell loss in type 1 diabetes. Nat Rev Endocrinol,2009,5(4):219-226.
[60]Yoon JW, Jun HS. Cellular and molecular pathogenic mechanisms of insulin-dependent diabetes mellitus. Ann N Y Acad Sci,2001,928(3):200-211.
[61]Mandrup-Poulsen T, Zumsteg U, Reimers J, et al. Involvement of interleukin 1 and interleukin 1 antagonist in pancreatic beta-cell destruction in insulin-dependent diabetes mellitus. Cytokine,1993,5(3):185-191.
[62]Donath MY, Boni-Schnetzler M, Ellingsgaard H, et al. Cytokine production by islets in health and diabetes:cellular origin, regulation and function. Trends Endocrinol Metab,2010,21(5):261-267.
[63]Ling Z, In't Veld PA, Pipeleers DG. Interaction of interleukin-1 with islet beta-cells. Distinction between indirect, aspecific cytotoxicity and direct, specific functional suppression. Diabetes,1993,42(1):56-65.
[64]Darville MI, Eizirik DL. Regulation by cytokines of the inducible nitric oxide synthase promoter in insulin-producing cells. Diabetologia,1998,41(9): 1101-1108.
[65]Yamada K, Takane-Gyotoku N, Yuan X, et al. Mouse islet cell lysis mediated by interleukin-1-induced Fas. Diabetologia,1996,39(11):1306-1312.
[66]Stassi G, Todaro M, Richiusa P, et al. Expression of apoptosis-inducing CD95 (Fas/Apo-1) on human beta-cells sorted by flow-cytometry and cultured in vitro. Transplant Proc,1995,27(6):3271-3275.
[67]Petrovsky N, Silva D, Socha L, et al. The role of Fas ligand in beta cell destruction in autoimmune diabetes of NOD mice. Ann N Y Acad Sci,2002, 958(4):204-208.
[68]Wachlin G, Augstein P, Schroder D, et al. IL-1beta, IFN-gamma and TNF-alpha increase vulnerability of pancreatic beta cells to autoimmune destruction. J Autoimmun,2003,20(4):303-312.
[69]Delaney CA, Green MH, Lowe JE, et al. Endogenous nitric oxide induced by interleukin-1 beta in rat islets of Langerhans and HIT-T15 cells causes significant DNA damage as measured by the 'comet' assay. FEBS Lett,1993, 333(3):291-295.
[70]Bolaffi JL, Rodd GG, Wang J, et al. Interrelationship of changes in islet nicotine adeninedinucleotide, insulin secretion, and cell viability induced by interleukin-1 beta. Endocrinology,1994,134(2):537-542.
[71]Mandrup-Poulsen T. The role of interleukin-1 in the pathogenesis of IDDM. Diabetologia,1996,39(9):1005-1029.
[72]Suk K, Kim S, Kim YH, et al. IFN-gamma/TNF-alpha synergism as the final effector in autoimmune diabetes:a key role for STAT1/IFN regulatory factor-1 pathway in pancreatic beta cell death. J Immunol,2001,166(7):4481-4489.
[73]Yang XD, Tisch R, Singer SM, et al. Effect of tumor necrosis factor alpha on insulin-dependent diabetes mellitus in NOD mice. I. The early development of autoimmunity and the diabetogenic process. Journal of Experimental Medicine, 1994,180(3):995-1004.
[74]Green EA, Flavell RA. Tumor necrosis factor-alpha and the progression of diabetes in non-obese diabetic mice. Immunol Rev,1999,169(3):11-22.
[75]Christen U, Wolfe T, Mohrle U, et al. A dual role for TNF-alpha in type 1 diabetes:islet-specific expression abrogates the ongoing autoimmune process when induced late but not early during pathogenesis. J Immunol,2001,166(12): 7023-7032.
[76]Lee LF, Xu B, Michie SA, et al. The role of TNF-alpha in the pathogenesis of type 1 diabetes in the nonobese diabetic mouse:analysis of dendritic cell maturation. Proc Natl Acad Sci U S A,2005,102(44):15995-16000.
[77]Richardson SJ, Willcox A, Bone AJ, et al. Immunopathology of the human pancreas in type-I diabetes. Semin Immunopathol,2011,33(1):9-21.
[78]Ban L, Zhang J, Wang L, et al. Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism. Proc Natl Acad Sci U S A,2008, 105(36):13644-13649.
[79]Foulis AK, McGill M, Farquharson MA. Insulitis in type 1 (insulin-dependent) diabetes mellitus in man--macrophages, lymphocytes, and interferon-gamma containing cells. J Pathol,1991,165(2):97-103.
[80]Rabinovitch A, Suarez-Pinzon WL, Sorensen O, et al. IFN-gamma gene expression in pancreatic islet-infiltrating mononuclear cells correlates with autoimmune diabetes in nonobese diabetic mice. J Immunol,1995,154(9): 4874-4882.
[81]Muir A, Peck A, Clare-Salzler M, et al. Insulin immunization of nonobese diabetic mice induces a protective insulitis characterized by diminished intraislet interferon-gamma transcription. J Clin Invest,1995,95(2):628-634.
[82]Sarvetnick N, Shizuru J, Liggitt D, et al. Loss of pancreatic islet tolerance induced by beta-cell expression of interferon-gamma. Nature,1990,346(6287): 844-847.
[83]Debray-Sachs M, Carnaud C, Boitard C, et al. Prevention of diabetes in NOD mice treated with antibody to murine IFN gamma. J Autoimmun,1991,4(2): 237-248.
[84]Nicoletti F, Meroni PL, Landolfo S, et al. Prevention of diabetes in BB/Wor rats treated with monoclonal antibodies to interferon-gamma. Lancet,1990, 336(8710):319.
[85]Campbell IL, Iscaro A, Harrison LC. IFN-gamma and tumor necrosis factor-alpha. Cytotoxicity to murine islets of Langerhans. J Immunol,1988, 141(7):2325-2329.
[86]Chang I, Cho N, Kim S, et al. Role of calcium in pancreatic islet cell death by IFN-gamma/TNF-alpha. J Immunol,2004,172(11):7008-7014.
[87]Hultgren B, Huang X, Dybdal N, et al. Genetic absence of gamma-interferon delays but does not prevent diabetes in NOD mice. Diabetes,1996,45(6): 812-817.
[88]Savinov AY, Wong FS, Chervonsky AV. IFN-gamma affects homing of diabetogenic T cells. J Immunol,2001,167(11):6637-6643.
[89]Amrani A, Verdaguer J, Thiessen S, et al. IL-1 alpha, IL-1beta, and IFN-gamma mark beta cells for Fas-dependent destruction by diabetogenic CD4+ T lymphocytes. J Clin Invest,2000,105(4):459-468.
[90]Thomas HE, Parker JL, Schreiber RD, et al. IFN-gamma action on pancreatic beta cells causes class I MHC upregulation but not diabetes. J Clin Invest,1998, 102(6):1249-1257.
[91]Sobel DO, Han J, Williams J, et al. Gamma interferon paradoxically inhibits the development of diabetes in the NOD mouse. J Autoimmun,2002,19(3): 129-137.
[92]Wang B, Andre I, Gonzalez A, et al. Interferon-gamma impacts at multiple points during the progression of autoimmune diabetes. Proc Natl Acad Sci U S A, 1997,94(25):13844-13849.
[93]Serreze DV, Post CM, Chapman HD, et al. Interferon-gamma receptor signaling is dispensable in the development of autoimmune type 1 diabetes in NOD mice. Diabetes,2000,49(12):2007-2011.
[94]Foulis AK, Farquharson MA, Meager A. Immunoreactive alpha-interferon in insulin-secreting beta cells in type 1 diabetes mellitus. Lancet,1987,2(8573): 1423-1427.
[95]Huang X, Yuang J, Goddard A, et al. Interferon expression in the pancreases of patients with type I diabetes. Diabetes,1995,44(6):658-664.
[96]Huang X, Hultgren B, Dybdal N, et al. Islet expression of interferon-alpha precedes diabetes in both the BB rat and streptozotocin-treated mice. Immunity, 1994,1(6):469-478.
[97]Stewart TA, Hultgren B, Huang X, et al. Induction of type I diabetes by interferon-alpha in transgenic mice. Science,1993,260(5116):1942-1946.
[98]Nakazawa T, Satoh J, Takahashi K, et al. Complete suppression of insulitis and diabetes in NOD mice lacking interferon regulatory factor-1. J Autoimmun, 2001,17(2):119-125.
[99]Devendra D, Eisenbarth GS. Interferon alpha--a potential link in the pathogenesis of viral-induced type 1 diabetes and autoimmunity. Clin Immunol, 2004,111(3):225-233.
[100]Devendra D, Jasinski J, Melanitou E, et al. Interferon-alpha as a mediator of polyinosinic:polycytidylic acid-induced type 1 diabetes. Diabetes,2005,54(9): 2549-2556.
[101]Peng RH, Paek E, Xia CQ, et al. Heightened interferon-alpha/beta response causes myeloid cell dysfunction and promotes T1D pathogenesis in NOD mice. Ann N Y Acad Sci,2006,1079(7):99-102.
[102]Li Q, Xu B, Michie SA, et al. Interferon-alpha initiates type 1 diabetes in nonobese diabetic mice. Proc Natl Acad Sci U S A,2008,105(34): 12439-12444.
[103]Stewart TA. Neutralizing interferon alpha as a therapeutic approach to autoimmune diseases. Cytokine Growth Factor Rev,2003,14(2):139-154.
[104]Sobel DO, Ahvazi B. Alpha-interferon inhibits the development of diabetes in NOD mice. Diabetes,1998,47(12):1867-1872.
[105]Tanaka-Kataoka M, Kunikata T, Takayama S, et al. Oral use of interferon-alpha delays the onset of insulin-dependent diabetes mellitus in nonobese diabetes mice. J Interferon Cytokine Res,1999,19(8):877-879.
[106]Brod SA. Ingested type I interferon:a potential treatment for autoimmunity. J Interferon Cytokine Res,2002,22(12):1153-1166.
[107]Harris PE, Malanga D, Liu Z, et al. Effect of interferon alpha on MHC class II gene expression in ex vivo human islet tissue. Biochim Biophys Acta,2006, 1762(6):627-635.
[108]Allison J, Oxbrow L, Miller JF. Consequences of in situ production of IL-2 for islet cell death.Int Immunol,1994,6(4):541-549.
[109]Pacheco-Silva A, Bastos MG, Muggia RA, et al. Interleukin 2 receptor targeted fusion toxin (DAB486-IL-2) treatment blocks diabetogenic autoimmunity in non-obese diabetic mice. Eur J Immunol,1992,22(3):697-702.
[110]Molano RD, Pileggi A, Berney T, et al. Long-term islet allograft survival in nonobese diabetic mice treated with tacrolimus, rapamycin, and anti-interleukin-2 antibody. Transplantation,2003,75(11):1812-1819.
[111]Serreze DV, Hamaguchi K, Leiter EH. Immunostimulation circumvents diabetes in NOD/Lt mice. J Autoimmun,1989,2(6):759-776.
[112]Zielasek J, Burkart V, Naylor P, et al. Interleukin-2-dependent control of disease development in spontaneously diabetic BB rats. Immunology,1990,69(2): 209-214.
[113]Shi FD, Flodstrom M, Balasa B, et al. Germ line deletion of the CD1 locus exacerbates diabetes in the NOD mouse. Proc Natl Acad Sci U S A,2001, 98(12):6777-6782.
[114]D'Cruz LM, Klein L. Development and function of agonist-induced CD25+Foxp3+ regulatory T cells in the absence of interleukin 2 signaling. Nat Immunol,2005,6(11):1152-1159.
[115]Yamanouchi J, Rainbow D, Serra P, et al. Interleukin-2 gene variation impairs regulatory T cell function and causes autoimmunity. Nat Genet,2007,39(3): 329-337.
[116]Tang Q, Adams JY, Penaranda C, et al. Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction. Immunity,2008, 28(5):687-697.
[117]McDaniel ML, Corbett JA, Kwon G, et al. A role for nitric oxide and other inflammatory mediators in cytokine-induced pancreatic beta-cell dysfunction and destruction. Advances in Experimental Medicine & Biology,1997, 426(5):313-319.
[118]Pitocco D, Zaccardi F, Di Stasio E, et al. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud,2010,7(1):15-25.
[119]Rabinovitch A, Suarez-Pinzon WL. Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus. Biochem Pharmacol,1998,55(8):1139-1149.
[120]Fields S, Song O. A novel genetic system to detect protein-protein interactions. Nature,1989,340(6230):245-246.
[121]Koegl M, Uetz P. Improving yeast two-hybrid screening systems. Brief Funct Genomic Proteomic,2007,6(4):302-312.
[122]Li JJ, Herskowitz I. Isolation of ORC6, a component of the yeast origin recognition complex by a one-hybrid system. Science,1993,262(5141): 1870-1874.
[123]SenGupta DJ, Zhang B, Kraemer B, et al. A three-hybrid system to detect RNA-protein interactions in vivo. Proc Natl Acad Sci U S A,1996,93(16): 8496-8501.
[124]Vidal M, Brachmann RK, Fattaey A, et al. Reverse two-hybrid and one-hybrid systems to detect dissociation of protein-protein and DNA-protein interactions. Proc Natl Acad Sci U S A,1996,93(19):10315-10320.
[125]Bennett MA, Shern JF, Kahn RA. Reverse two-hybrid techniques in the yeast Saccharomyces cerevisiae. Methods Mol Biol,2004,261 (2):313-326.
[126]Serebriiskii I, Khazak V, Golemis EA. A two-hybrid dual bait system to discriminate specificity of protein interactions. J Biol Chem,1999,274(24): 17080-17087.
[127]Serebriiskii IG, Kotova E. Analysis of protein-protein interactions utilizing dual bait yeast two-hybrid system. Methods Mol Biol,2004,261 (7):263-296.
[128]Aronheim A. Improved efficiency sos recruitment system:expression of the mammalian GAP reduces isolation of Ras GTPase false positives. Nucleic Acids Res,1997,25(16):3373-3374.
[129]Johnsson N, Varshavsky A. Split ubiquitin as a sensor of protein interactions in vivo. Proc Natl Acad Sci U S A,1994,91(22):10340-10344.
[130]Schonhofer-Merl S, Torres-Ruiz RA. The Sos-recruitment system as a tool to analyze cellular localization of plant proteins:membrane localization of Arabidopsis thaliana PEPINO/PASTICCINO2. Mol Genet Genomics,2010, 283(5):439-449.
[131]Huang W, Wang SL, Lozano G, et al. cDNA library screening using the SOS recruitment system. Biotechniques,2001,30(1):94-98,100.
[132]Snider J, Kittanakom S, Curak J, et al. Split-ubiquitin based membrane yeast two-hybrid (MYTH) system:a powerful tool for identifying protein-protein interactions. J Vis Exp,2010,36(6):112-115
[133]Wehr MC, Laage R, Bolz U, et al. Monitoring regulated protein-protein interactions using split TEV. Nat Methods,2006,3(12):985-993.
[134]Luo Y, Batalao A, Zhou H, et al. Mammalian two-hybrid system:a complementary approach to the yeast two-hybrid system. Biotechniques,1997, 22(2):350-352.
[135]Lee JW, Lee SK. Mammalian two-hybrid assay for detecting protein-protein interactions in vivo. Methods Mol Biol,2004,261(7):327-336.
[136]Shui X, Lu X, Gao Y, et al. A mammalian two-hybrid system-based assay for small-molecular HIV fusion inhibitors targeting gp41. Antiviral Res,2011,90(1): 54-63.
[137]Karimova G, Pidoux J, Ullmann A, et al. A bacterial two-hybrid system based on a reconstituted signal transduction pathway. Proc Natl Acad Sci U S A,1998, 95(10):5752-5756.
[138]Battesti A, Bouveret E. Improvement of bacterial two-hybrid vectors for detection of fusion proteins and transfer to pBAD-tandem affinity purification, calmodulin binding peptide, or 6-histidine tag vectors. Proteomics,2008,8(22): 4768-4771.
[139]Engelender S, Kaminsky Z, Guo X, et al. Synphilin-1 associates with alpha-synuclein and promotes the formation of cytosolic inclusions. Nat Genet, 1999,22(1):110-114.
[140]Soehn AS, Franck T, Biskup S, et al. Periphilin is a novel interactor of synphilin-1, a protein implicated in Parkinson's disease. Neurogenetics,2010, 11(2):203-215.
[141]Park UH, Kim EJ, Um SJ. A novel cytoplasmic adaptor for retinoic acid receptor (RAR) and thyroid receptor functions as a Derepressor of RAR in the absence of retinoic acid. J Biol Chem,2010,285(44):34269-34278.
[142]Moerdyk-Schauwecker M, Destephanis D, Hastie E, et al. Detecting protein-protein interactions in vesicular stomatitis virus using a cytoplasmic yeast two hybrid system. J Virol Methods,2011,173(2):203-212.
[143]Shi YH, Chen J, Li CH, et al. The establishment of a library screening method based on yeast two-hybrid system and its use to determine the potential interactions of liver proteins in ayu, Plecoglossus altivelis. Fish Shellfish Immunol,2011,30(4-5):1184-1187.
[144]Ito T, Chiba T, Ozawa R, et al. A comprehensive two-hybrid analysis to explore the yeast protein interactome. Proc Natl Acad Sci U S A,2001,98(8): 4569-4574.
[145]Parrish JR, Yu J, Liu G, et al. A proteome-wide protein interaction map for Campylobacter jejuni. Genome Biol,2007,8(7):R130.
[146]Hackbusch J, Richter K, Muller J, et al. A central role of Arabidopsis thaliana ovate family proteins in networking and subcellular localization of 3-aa loop extension homeodomain proteins. Proc Natl Acad Sci U S A,2005,102(13): 4908-4912.
[147]Formstecher E, Aresta S, Collura V, et al. Protein interaction mapping:a Drosophila case study. Genome Res,2005,15(3):376-384.
[148]Li S, Armstrong CM, Bertin N, et al. A map of the interactome network of the metazoan C. elegans. Science,2004,303(5657):540-543.
[149]Uetz P, Dong YA, Zeretzke C, et al. Herpesviral protein networks and their interaction with the human proteome. Science,2006,311(5758):239-242.
[150]Johansson M, Brooks AJ, Jans DA, et al. A small region of the dengue virus-encoded RNA-dependent RNA polymerase, NS5, confers interaction with both the nuclear transport receptor importin-beta and the viral helicase, NS3. J Gen Virol,2001,82(Pt 4):735-745.
[151]Vasudevan SG, Johansson M, Brooks AJ, et al. Characterisation of inter-and intra-molecular interactions of the dengue virus RNA dependent RNA polymerase as potential drug targets. Farmaco,2001,56(1-2):33-36.
[152]Bartel P, Chien CT, Sternglanz R, et al. Elimination of false positives that arise in using the two-hybrid system. Biotechniques,1993,14(6):920-924.
[153]von Mering C, Krause R, Snel B, et al. Comparative assessment of large-scale data sets of protein-protein interactions. Nature,2002,417(6887):399-403.
[154]Ratushny V, Golemis E. Resolving the network of cell signaling pathways using the evolving yeast two-hybrid system. Biotechniques,2008,44(5):655-662.
[155]Rajagopala SV, Titz B, Goll J, et al. The protein network of bacterial motility. Mol Syst Biol,2007,3(2):128.
[156]Fashena SJ, Serebriiskii I, Golemis EA. The continued evolution of two-hybrid screening approaches in yeast:how to outwit different preys with different baits. Gene,2000,250(1-2):1-14.
[157]Vidalain PO, Boxem M, Ge H, et al. Increasing specificity in high-throughput yeast two-hybrid experiments. Methods,2004,32(4):363-370.
[158]Stellberger T, Hauser R, Baiker A, et al. Improving the yeast two-hybrid system with permutated fusions proteins:the Varicella Zoster Virus interactome. Proteome Sci,2010,8(1):8.
[159]Chen YC, Rajagopala SV, Stellberger T, et al. Exhaustive benchmarking of the yeast two-hybrid system. Nat Methods,2010,7(9):667-668;author reply 668.
[160]Wang W, Huang B, Feng ZG, et al. Expression, purification, and characterization of functional recombinant human daintain/AIF-1 in Escherichia coli. Z Naturforsch C,2010,65(11-12):726-732.
[161]赵燕英.Daintain/AIF-1在1型糖尿病发生中的作用：[博士学位论文].保存地点：华中科技大学图书馆,2009
[162]James P, Halladay J, Craig EA. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast. Genetics,1996,144(4): 1425-1436.
[163]Fu K, Zhao YY, Tang WX, et al. Preparation and identification of monoclonal antibodies against daintain. Hybridoma (Larchmt),2006,25(2):95-97.
[164]付康,程首超,刘收等.人同种异体移植炎症因子-1的基因克隆及其在小鼠成纤维细胞中的表达.华中科技大学学报(医学版),2007,36(5)：663-666.
[165]Yoon JW, Jun HS. Autoimmune destruction of pancreatic beta cells. Am J Ther, 2005,12(6):580-591.
[166]Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods,1983, 65(1-2):55-63.
[167]Green LC, Wagner DA, Glogowski J, et al. Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal Biochem,1982,126(1):131-138.
[168]Lee BW, Kwon SJ, Chae HY, et al. Dose-related cytoprotective effect of alpha-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells. Free Radic Res,2009,43(1):68-77.
[169]Kolb H, Kolb-Bachofen V. Type 1 (insulin-dependent) diabetes mellitus and nitric oxide. Diabetologia,1992,35(8):796-797.
[170]Eizirik DL, Pavlovic D. Is there a role for nitric oxide in beta-cell dysfunction and damage in IDDM? Diabetes Metab Rev,1997,13(4):293-307.
[171]Hamid M, McCluskey JT, McClenaghan NH, et al. Comparison of the secretory properties of four insulin-secreting cell lines. Endocrine Research,2002,28(1-2): 35-47.
[172]Asfari M, Janjic D, Meda P, et al. Establishment of 2-mercaptoethanol-dependent differentiated insulin-secreting cell lines. Endocrinology,1992,130(1):167-178.
[173]Skelin M, Rupnik M, Cencic A. Pancreatic beta cell lines and their applications in diabetes mellitus research. ALTEX,2010,27(2):105-113.
[174]Thomas HE, Darwiche R, Corbett JA, et al. Interleukin-1 plus gamma-interferon-induced pancreatic beta-cell dysfunction is mediated by beta-cell nitric oxide production. Diabetes,2002,51(2):311-316.
[175]Autieri MV. cDNA cloning of human allograft inflammatory factor-1:tissue distribution, cytokine induction, and mRNA expression in injured rat carotid arteries. Biochem Biophys Res Commun,1996,228(1):29-37.
[176]Autieri MV, Chen X. The ability of AIF-1 to activate human vascular smooth muscle cells is lost by mutations in the EF-hand calcium-binding region. Exp Cell Res,2005,307(1):204-211.
[177]Henquin JC. Regulation of insulin secretion:a matter of phase control and amplitude modulation. Diabetologia,2009,52(5):739-751.
[178]Janjic D, Asfari M. Effects of cytokines on rat insulinoma INS-1 cells. J Endocrinol,1992,132(1):67-76.