Abstract
Abstract Excessive accumulation of collagen contributes to the fibrotic process. Several experimental studies have shown that interferon (IFN)-γ is effective in preventing fibrogenesis. Interleukin-18, formerly called IFN-γ -inducing factor, is a key mediator of inflammation and host defense responses. Here, we investigated the regulatory effect of IL-18 on expression of type I and collagen genes in dermal fibroblasts. Exposure of human dermal fibroblasts (HDF) to IL-18 resulted in a reduction of collagen gene expression and protein production was in a dose-dependent manner using real-time RT-PCR and Sircol assay. Next, we determined the signaling pathways involved by small interfering RNA(siRNA), reporter assay, and Western blotting. Silencing of the Ets-1 reversed inhibitory effects of IL-18. We demonstrated that IL-18 induced phosphorylation of extracellular signal-regulated kinase (ERK) within 10 minutes, and inhibitor of ERK blocked the inhibitory effects of IL-18. These results suggest that L-18 downregulates collagen production in HDF directly via Ets-1-dependent pathway and ERK pathway.
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