IL-18 downregulates collagen production in human dermal fibroblasts via the ERK pathway

Hee Jung Kim, Seok Bean Song, Jung Min Choi, Kyung Moon Kim, Baik Kee Cho, Dae Ho Cho, Hyun Jeong Park

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Excessive accumulation of collagen contributes to the fibrotic process. Several experimental studies have shown that IFN-γ is effective in preventing fibrogenesis. IL-18, originally identified as an IFN-γ-inducing factor, is a key mediator of inflammation and host defense responses. In this study, we investigated the regulatory effect of IL-18 on the expression of type I and III collagen genes in dermal fibroblasts. The exposure of human dermal fibroblasts (HDFs) to IL-18 resulted in a reduction of collagen gene expression and production. Also, IL-18 inhibited the fibrogenic cytokine transforming growth factor (TGF)-Β-induced collagen gene expression. Next, to determine the molecular mechanism involved in this regulation, we showed that IL-18-regulated collagen expression was blocked by small interfering RNA (siRNA)-mediated Ets-1 knockdown. Furthermore, we showed that IL-18 induced phosphorylation of extracellular signal-regulated kinase (ERK) within 10 minutes and that the ERK inhibitor PD98059 blocked the inhibitory effect of IL-18. IL-18 also inhibited the production of collagen in systemic sclerosis (SSc) dermal fibroblasts. Our data indicate that IL-18 downregulates collagen production in HDF directly via Ets-1 and the ERK pathway, suggesting that IL-18 may exert antifibrotic activities in dermal fibroblasts.

Original languageEnglish
Pages (from-to)706-715
Number of pages10
JournalJournal of Investigative Dermatology
Volume130
Issue number3
DOIs
Publication statusPublished - 2010 Mar

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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