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.
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.
Department of Pediatrics, The Third Hospital of Hebei Medical University, Shijiazhuang, China. gracezhangyaping@yahoo.com.cn
Yaping
Y
Zhang
Xixian
X
Yao
D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D024042:Collagen Type I / Q000096:biosynthesis*; D024202:Electrophoretic Mobility Shift Assay; D055166:Hepatic Stellate Cells / Q000201:enzymology / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008103:Liver Cirrhosis / Q000201:enzymology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000873:Anthracenes; D024042:Collagen Type I; D007093:Imidazoles; D053583:Interleukin-1beta; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D018808:Transcription Factor AP-1; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; C093642:SB 203580