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

作者：Lutz H H; Sackett S D; Kroy D C; Gassler N; Trautwein C^*

来源：European Journal of Cell Biology, 2012, 91(6-7): 576-581.

DOI：10.1016/j.ejcb.2011.09.006

• gp130
• LysMCre
• Concanavalin A
• Hepatitis
• IL-6
• Macrophages

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(Delta Lys), KO) animals and analyzed its relevance in modulating Con A-induced hepatitis. Additionally, we performed in vitro studies with gp130(Delta Lys)-macrophages. We demonstrate that gp130(Delta 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(Delta 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(Delta Lys) animals. Interestingly, the LPS-dependent IL-6 release in gp130(Delta Lys) macrophages is significantly reduced (p %26lt; 0.05) compared to WT macrophages. Additionally, IL-6 blood levels in vivo after Con A injection were significantly lower in gp130(Delta Lys) animals compared to WT animals (p %26lt; 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.

• 出版日期2012-7