Abstract: Aim To investigate the effects of IL-4 on collagen type I mRNA expression and protein production, and the roles of Janus kinase/signal transducers and activators transcription(JAK/STAT) signaling transduction pathway in increased collagen type I mRNA expression stimulated by IL-4 in activated hepatic stellate cells(HSCs). Methods First, collagen type I mRNA expression and protein production induced by IL-4 at different doses in a human HSC cell line, LX-2 was determined by RT-PCR and ELISA. Second, the effects of JAK inhibitor AG490 on JAK1 phosphorylation and collagen type I mRNA expression stimulated by IL-4 were detected by Western blot and RT-PCR. Third, the roles of transfection with STAT6 antisense oligonucleotide (STAT6-ASON) in STAT6 phosphorylation after IL-4 were detected by Western blot. Finally, the effect of transfection with STAT6-ASON on collagen type I mRNA expression after IL-4 was measured by RT-PCR. Results IL-4 increased collagen type I mRNA expression and protein production in a dose-dependent manner in LX-2, reaching a maximal level at 50 ng/ml IL-4. In addition, JAK inhibitor AG490 completely blocked JAK1 and STAT6 phosphorylation and increase in collagen type I gene expression after IL-4 in LX-2. Transfection with STAT6-ASON blocked STAT6 phosphorylation and increased collagen type I mRNA by IL-4 in LX-2. Conclusion JAK/STAT signaling pathway had mediated IL-4-induced collagen type I mRNA expression and protein production in activated HSC.

Key words: IL-4, Hepatic stellate cell(HSC), JAK/STAT signaling pathway, Collagen type I