Details

Autor(en) / Beteiligte

• Nakano, Toshiaki
• Goto, Shigeru
• Lai, Chia-Yun
• Hsu, Li-Wen
• Takaoka, Yuki
• Kawamoto, Seiji
• Chiang, Kuei-Chen
• Shimada, Yayoi
• Ohmori, Naoya
• Goto, Takeshi
• Sato, Shuji
• Ono, Kazuhisa
• Cheng, Yu-Fan
• Chen, Chao-Long

Titel

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

Ist Teil von

• Immunology, 2010-04, Vol.129 (4), p.547-555

Ort / Verlag

Oxford, UK: Oxford, UK : Blackwell Publishing Ltd

Erscheinungsjahr

2010

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• 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-κB 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-κB and calcineurin signalling.