AKT regulates IL-1β-induced proliferation and activation of hepatic stellate cells

Background:Activated hepatic stellate cells(HSCs)are closely involved in the initiation,perpetuation,and resolution of liver fibrosis.Pro-inflammatory cytokine levels are positively correlated with the transition from liver injury to fibrogenesis and contribute to HSC pathophysiology in liver fibrosis.Methods:In this study,we investigated the effect of the pro-inflammatory cytokine interleukin(IL)-1βon the proliferation and signaling pathways involved in fibrogenesis in LX-2 cells,an HSC cell line,using western blotting and cell proliferation assays.Results:IL-1βincreased the proliferation rate andα-smooth muscle actin(SMA)expression of LX-2 cells in a dose-dependent manner.Within 1 h after IL-1βtreatment,c-Jun N-terminal kinase(JNK),p38,and nuclear factor-κB(NF-κB)signaling was activated in LX-2 cells.Subsequently,protein kinase B(AKT)phosphorylation and an increase inα-SMA expression were observed in LX-2 cells.Each inhibitor of JNK,p38,or NF-κB decreased cell proliferation,AKT phosphorylation,andα-SMA expression in IL-1β-treated LX-2 cells.Conclusion:These results indicate that JNK,p38,and NF-κB signals converge at AKT phosphorylation,leading to LX-2 activation by IL-1β.Therefore,the AKT signaling pathway can be used as a target for alleviating liver fibrosis by the inflammatory cytokine IL-1β.