Zhang Y, Yao X. Role of c-Jun N-terminal kinase and p38/activation protein-1 in interleukin-1β-mediated type I collagen synthesis in rat hepatic stellate cells. APMIS 2011.
Interleukin-1 (IL-1) may play a role in maintaining hepatic stellate cell (HSC) in activated state that is responsible for hepatic fibrogenesis. However, the signal transduction pathway that is stimulated by IL-1 in HSC remains to be fully elucidated. The aims of this study were to investigate the role of c-Jun N-terminal kinase (JNK) and p38/activation protein (AP-1) in IL-1β-mediated type I collagen synthesis in rat HSCs. Here, we show that IL-1β could activate JNK and p38 in a time-dependent manner, and that inhibition of the JNK pathway could increase collagen synthesis; however, inhibition of the p38 pathway could inhibit collagen synthesis. Furthermore, IL-1β activated AP-1 in a time-dependent manner in rat HSCs. These data demonstrate that L-1β could promote the synthesis of type I collagen in rat HSCs, and the JNK and p38/AP-1 pathways were involved in this process. In summary, IL-1β-induced collagen synthesis is possibly mediated by cytoplasmic JNK and p38/AP-1 pathways. Therefore, drugs that block the p38/AP-1 pathway may inhibit liver extracellular matrix synthesis and suppress liver fibrosis.