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

Abstract

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)-1(3 on 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-1(3 increased the proliferation rate and a-smooth muscle actin (SMA) expression of LX-2 cells in a dose-dependent manner. Within 1 h after IL-1(3 treatment, c-Jun N-terminal kinase (JNK), p38, and nuclear factor-KB (NF-KB) signaling was activated in LX-2 cells. Subsequently, protein kinase B (AKT) phosphorylation and an increase in aSMA expression were observed in LX-2 cells. Each inhibitor of JNK, p38, or NF-KB decreased cell proliferation, AKT phosphorylation, and a-SMA expression in IL-1(3-treated LX-2 cells. Conclusion: These results indicate that JNK, p38, and NF-KB signals converge at AKT phosphorylation, leading to LX-2 activation by IL-1(3. Therefore, the AKT signaling pathway can be used as a target for alleviating liver fibrosis by the inflammatory cytokine IL-1(3.