Immunological aspects and therapeutic significance of an autoantibody against histone H1 in a rat model of concanavalin A-induced hepatitis

被引：23

作者：

Nakano, Toshiaki ^{[1
,2
,3
]}

Goto, Shigeru ^{[1
,4
]}

Lai, Chia-Yun ^{[1
]}

Hsu, Li-Wen ^{[1
]}

Takaoka, Yuki ^{[5
]}

Kawamoto, Seiji ^{[5
]}

Chiang, Kuei-Chen ^{[6
]}

Shimada, Yayoi ^{[6
]}

Ohmori, Naoya ^{[6
,7
]}

Goto, Takeshi ^{[6
,7
]}

Sato, Shuji ^{[6
,7
]}

Ono, Kazuhisa ^{[5
]}

Cheng, Yu-Fan ^{[8
]}

Chen, Chao-Long ^{[1
]}

机构：

[1] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Surg,Kaohsiung Med Ctr, Kaohsiung 833, Taiwan

[2] Chang Gung Univ, Coll Med,Transplantat & Regenrat Med Core Lab, Chang Gung Mem Hosp, Kaohsiung Med Ctr,Dept Med Res, Kaohsiung 833, Taiwan

[3] Chang Gung Univ, Coll Med, Grad Inst Clin Med Sci, Kaohsiung, Taiwan

[4] Iwao Hosp, Oita, Japan

[5] Hiroshima Univ, Dept Mol Biotechnol, Grad Sch Adv Sci Matter, Higashihiroshima 724, Japan

[6] Josai Int Univ, Kazusa Inst Drug Discovery, Chiba, Japan

[7] Josai Int Univ, Fac Pharmaceut Sci, Chiba, Japan

[8] Chang Gung Univ, Coll Med, Chang Gung Mem Hosp, Dept Diagnost Radiol,Kaohsiung Med Ctr, Kaohsiung 833, Taiwan

来源：

IMMUNOLOGY | 2010年 / 129卷 / 04期

关键词：

autoantibodies; autoimmunity; liver immunology; disease; T-CELL-ACTIVATION; MOBILITY GROUP BOX-1; N-TERMINAL-KINASE; LIVER-TRANSPLANTATION; DENDRITIC CELLS; ANTINUCLEAR ANTIBODIES; ORGAN-TRANSPLANTATION; IMMUNE-RESPONSE; ALLOGRAFTS; REGENERATION;

D O I：

10.1111/j.1365-2567.2009.03149.x

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

P>We previously demonstrated the immunosuppressive activity of anti-histone H1 autoantibody induced in experimental and clinical liver allograft tolerance. This study aimed to explore the immunological aspects of anti-histone H1 autoantibody in liver injury induced by concanavalin A (Con A). To establish a Con A-hepatitis model, 20 mg/kg Con A was intravenously injected into rats, after which liver function and histopathological analyses were performed. In this model, anti-histone H1 autoantibody was transiently induced in the sera during the natural recovery stage, 3-7 days after Con A injection. To evaluate the therapeutic significance of anti-histone H1 autoantibody, a polyclonal antibody against histone H1 was intraperitoneally injected immediately after Con A injection. We found that injection of anti-histone H1 antibody could reduce Con A-induced liver damage. Further mechanical analyses revealed that anti-histone H1 antibody altered the intracellular activation of mitogen-activated protein kinase, nuclear factor-kappa B and calcineurin via T-cell receptor signalling, suggesting that anti-histone H1 antibody may protect the liver from Con A-induced injury by inhibiting activation of effector T cells. These findings suggest that anti-histone H1 autoantibody may be a natural immune regulatory factor that protects inflamed livers suffering from autoimmune hepatitis and may lead to T-cell unresponsiveness through the selective regulation of mitogen-activated protein kinase/nuclear factor-kappa B and calcineurin signalling.

引用

页码：547 / 555

页数：9

共 40 条

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