Endogenous αCGRP protects against concanavalin A-induced hepatitis in mice
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- 作者：Akiko Kamiyoshi ; Takayuki Sakurai ; Yuka Ichikawa-Shindo ; Junichi Fukuchi ; Hisaka Kawate ; Shin-ichi Muto ; Yoh-ichi Tagawa and Takayuki Shindo
- 关键词：CGRP ; Knockout mice ; Liver ; Hepatitis ; Apoptosis ; IL-6
- 刊名：Biochemical and Biophysical Research Communications
- 出版年：2006
- 出版时间：28 April 2006
- 年：2006
- 卷：343
- 期：1
- 页码：152-158
- 全文大小：1853 K
文摘
To evaluate hepatoprotective effect of α-calcitonin gene-related peptide (αCGRP), we compared the susceptibilities of αCGRP−/− and wild-type mice to concanavalin A (Con A)-induced hepatitis. Twelve hours after Con A administration, serum transaminases were markedly higher in αCGRP−/− than wild-type mice, and much more extensive TUNEL-positive lesions and DNA fragmentation were detected in the livers of αCGRP−/− mice. Notably, expression of IL-6 was selectively diminished in αCGRP−/− mice, suggesting that induction of IL-6 during acute inflammatory responses is blunted in αCGRP−/− mice. In addition, primary cultured αCGRP−/− hepatocytes were more susceptible to IFN-γ-induced cell death than hepatocytes from wild-type mice. Administration of exogenous αCGRP reduced the incidence of apoptosis among hepatocytes and endothelial cells. It thus appears that αCGRP exerts a hepatoprotective effect by modulating cytokine expression and preventing apoptosis.