TIMP-1 expression induced by IL-32 is mediated through activation of AP-1 signal pathway

Hepatic fibrosis is a necessarily stage from the progression of chronic liver diseases to cirrhosis, even hepatocellular carcinoma (HCC). Hepatic fibrosis is characterized by the progressive accumulation of extracellular matrix (ECM). The balance between ECM production and degradation is mediated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 is an important regulator in the synthesis and degradation of ECM. IL-32, a multi-function cytokine, could induce IL-1β, IL-6, IL-8 and other cytokine expressions by activating AP-1, NF-κβ, p38MAPK signal pathways. IL-32 expression is increased in liver tissues of hepatic fibrosis. However, the role of IL-32 in the pathogenesis of liver fibrosis is not thoroughly clear. Recently, it is demonstrated that TIMP-1 expression is induced by the activation of AP-1 signal pathway. So we assayed the effect of IL-32 on TIMP-1 expression by LX-2 cells (one of HSCs cell lines) in the present study. We found that IL-32 could induce TIMP-1 expression by LX-2 cells at a dose-dependent manner. IL-32 could increase TIMP-1 promoter activity and induce TIMP-1 expression by activating AP-1 signal pathway. Moreover, the increase of TIMP-1 expression could promote the migration of LX-2 cells. In conclusion, we believe that IL-32 might be involved in the pathogenesis of hepatic fibrosis by inducing TIMP-1 expression.

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