Deletion of gp130 in myeloid cells modulates IL-6-release and is associated with more severe liver injury of Con A hepatitis

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• 作者：H.H. Lutz^a ; S.D. Sackett^a ; D.C. Kroy^a ; ^c ; N. Gassler^b ; C. Trautwein^a ; ^{ctrautwein@ukaachen.de}
• 关键词：gp130 ; LysMCre ; Concanavalin A ; Hepatitis ; IL-6 ; Macrophages
• 刊名：European Journal of Cell Biology
• 出版年：2012
• 期刊代码：15_01719335
• 类别：bio
• 出版时间：June-July, 2012
• 卷：91
• 期：6-7
• 页码：576-581
• 文件大小：1040 K

摘要

IL-6/gp130 dependent signaling plays an important role in modulating inflammation in acute and chronic diseases. The course of Concanavalin A- (Con A) induced hepatitis can be modulated by different immune-mediated mechanisms. IL-6/gp130-dependent signaling has been shown to be protective in hepatocytes. However, the role of this pathway in myeloid cells has not yet been studied. In our present study we used macrophage/neutrophil-specific gp130 knockout (gp130^螖Lys, KO) animals and analyzed its relevance in modulating Con A-induced hepatitis. Additionally, we performed in vitro studies with gp130^螖Lys-macrophages. We demonstrate that gp130^螖Lys animals are more susceptible to Con A-induced hepatitis. This is reflected by higher transaminases, higher lethality and more severe liver injury as shown by histological staining. Using flow cytometry analysis we further could show that increased liver injury of gp130^螖Lys animals is associated with a stronger infiltration of CD11b/F4/80 double-positive cells compared to wild-type (gp130^flox/flox, WT) controls. To further characterize our observations we studied thioglycolate-elicited peritoneal macrophages from gp130^螖Lys animals. Interestingly, the LPS-dependent IL-6 release in gp130^螖Lys macrophages is significantly reduced (p < 0.05) compared to WT macrophages. Additionally, IL-6 blood levels in vivo after Con A injection were significantly lower in gp130^螖Lys animals compared to WT animals (p < 0.05). In summary, our results suggest that gp130-deletion in macrophages and granulocytes leads to diminished IL-6 release from these cells, which is associated with more severe Con A-induced hepatitis.