Department of Pediatrics, The Third Hospital of Hebei Medical University, Shijiazhuang, China.
APMIS. 2012 Feb;120(2):101-7. doi: 10.1111/j.1600-0463.2011.02816.x. Epub 2011 Oct 6.
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.
白细胞介素-1 (IL-1) 可能在维持活化的肝星状细胞 (HSC) 中发挥作用，而活化的 HSC 是肝纤维化形成的主要原因。然而，IL-1 刺激 HSC 中所涉及的信号转导途径仍未完全阐明。本研究旨在探讨 c-Jun N-末端激酶 (JNK) 和 p38/激活蛋白 (AP-1) 在 IL-1β介导的大鼠 HSCs Ⅰ型胶原合成中的作用。在这里，我们发现 IL-1β可以在时间依赖性的方式下激活 JNK 和 p38，并且 JNK 通路的抑制可以增加胶原合成；然而，p38 通路的抑制可以抑制胶原合成。此外，IL-1β可以在时间依赖性的方式下激活大鼠 HSCs 中的 AP-1。这些数据表明，IL-1β可以促进大鼠 HSCs 中 I 型胶原的合成，而 JNK 和 p38/AP-1 途径参与了这一过程。总之，IL-1β诱导的胶原合成可能是通过细胞质 JNK 和 p38/AP-1 途径介导的。因此，阻断 p38/AP-1 途径的药物可能会抑制肝脏细胞外基质的合成并抑制肝纤维化。
