Effect of IL‐4 and IL‐13 on collagen production in cultured LI90 human hepatic stellate cells

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Abstract
Background: Recently, it has been reported that interleukin 4 (IL‐4) and 13 (IL‐13) directly activate fibroblasts and promote fibrosis. In the process of hepatic fibrosis, the effects of these cytokines on hepatic stellate cells (HSCs) are not well known. Methods: We evaluated the effects of IL‐4 and IL‐13 on the collagen production and the proliferation of LI90, a hepatic stellate cell line. We also examined whether interferon (IFN) interferes with the expression of collagen, since IFN has been reported to clinically suppress hepatic fibrosis. Results: The receptor complex for IL‐4 and IL‐13 was IL‐4Rα/IL‐13Rα1 on LI90 cells, and the phosphorylation of Stat6 was induced by IL‐4 and IL‐13. The treatment of LI90 cells with IL‐4 or IL‐13 increased the production of collagen I protein levels by nearly three times in comparison with untreated cells. Collagen mRNA levels were increased roughly 10‐fold by IL‐4 and 100‐fold by IL‐13. Interestingly, BrdU incorporation in LI90 cells was decreased by IL‐4 or IL‐13 treatment. Furthermore, induction of collagen I production by these cytokines was blocked by IFNα or IFNβ treatment, although neither treatment alone suppressed collagen production. Conclusions: Our data suggested that IL‐4 and IL‐13 directly affected HSCs by increasing collagen production and suppressing cell proliferation. The anti‐fibrogenetic effect of IFN may be due in part to the blockade of IL‐4 and IL‐13 stimulation of HSCs.