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

Abstract

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.

Protective effects of baicalin on rabbit articular chondrocytes in vitro

“…Previous studies have demonstrated that baicalin may decrease levels of interleukin (IL)-1β (19) and depress the expression of collagen type I (20). As IL-1β is a pro-inflammatory agent and collagen type I expression is an indicator of dedifferentiation (21), baicalin may have a positive effect on inflammation and the dedifferentiation of chondrocytes.…”

IL-1 receptor antagonist ameliorates inflammasome-dependent alcoholic steatohepatitis in mice

“…Our data and reports of others demonstrate that the mechanisms by which IL-1β exerts its pathogenic effects involve sensitization of hepatocytes to cytotoxicity induced by TNF-α (14,29), upregulation of lipid synthesis in hepatocytes (12), activation of hepatic stellate cells (30), maintenance of macrophages in inflammatory state (31), and feed-forward induction of LPS-inducible inflammatory cytokines (17), such as TNF-α or MCP-1, that are crucial in ALD (24,32). Our results also demonstrated that even very low concentrations of IL-1β exerted significant biological effects on hepatocytes and macrophages, thus giving additional support to the crucial role of IL-1β in ALD, even at the relatively low absolute serum levels of IL-1β in vivo.…”

Tracking anti‐fibrotic pathways of nilotinib and imatinib in experimentally induced liver fibrosis: An insight

“…27 It is involved in the perpetuation of HSC activation resulting in hepatic fibrogenesis as a functional change. 28 It also promotes the deposition of ECM. 29 In the present study, levels of both IL-1 subtypes (a and b) were lowered by nilotinib and imatinib at the doses tested.…”