IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway
- Authors
- Kim, Hee Jung; Song, Seok Bean; Choi, Jung Min; Kim, Kyung Moon; Cho, Baik Kee; Cho, Dae Ho; Park, Hyun Jeong
- Issue Date
- Mar-2010
- Publisher
- NATURE PUBLISHING GROUP
- Citation
- JOURNAL OF INVESTIGATIVE DERMATOLOGY, v.130, no.3, pp 706 - 715
- Pages
- 10
- Journal Title
- JOURNAL OF INVESTIGATIVE DERMATOLOGY
- Volume
- 130
- Number
- 3
- Start Page
- 706
- End Page
- 715
- URI
- https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13254
- DOI
- 10.1038/jid.2009.302
- ISSN
- 0022-202X
1523-1747
- Abstract
- Excessive accumulation of collagen contributes to the fibrotic process. Several experimental studies have shown that IFN-gamma is effective in preventing fibrogenesis. IL-18, originally identified as an IFN-gamma-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)-beta-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.
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