Up-regulation of hepatic heme oxygenase-1 expression by locally induced interleukin-6 in rats administered carbon tetrachloride intraperitoneally

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• 作者：Kenzaburo Yamaji ; Yosuke Ochiai ; Ken-ichi Ohnishi ; Ayako Yawata ; Toshiyuki Chikuma ; Hiroshi Hojo
• 关键词：Carbon tetrachloride ; Heme oxygenase-1 ; Interleukin-6 ; Liver injury
• 刊名：Toxicology Letters
• 出版年：2008
• 出版时间：10 July 2008
• 年：2008
• 卷：179
• 期：3
• 页码：124-129
• 全文大小：445 K

文摘

We previously reported that interleukin-6 (IL-6) was locally produced in the early period after intraperitoneal (i.p.) or subcutaneous carbon tetrachloride (CCl₄) administration, but not after oral (p.o.) administration. In the present study, we focused on the up-regulation of stress-inducible proteins induced by IL-6 after i.p. CCl₄ administration. The expression of heme oxygenase-1 (HO-1) (EC 1.14.99.3) mRNA and protein were induced more in rats administered CCl₄ via the i.p. route, compared with the p.o. route; however, expression of heat shock protein (HSP) 72 and HSP90 mRNA were increased to similar extents in both experimental groups. The induction of HO-1 mRNA and protein after i.p. CCl₄ administration were significantly reduced after pretreatment with anti-rat IL-6 antibody. Activation of the signal transducer and activator of transcription factor 3 (STAT3), which promotes HO-1 expression, peaked together with plasma levels of IL-6 after i.p. CCl₄ administration, suggesting that hepatic HO-1 expression was increased by IL-6 via the Janus kinase/STAT3 pathway. The present data indicate that hepatic HO-1 is up-regulated by endogenously produced IL-6, in addition to its up-regulation by heme derived from cytochrome P450 which has already been reported in rats administered i.p. CCl₄. The up-regulation of hepatic HO-1 expression may reduce the tissue injury to livers caused by CCl₄.