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IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway

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dc.contributor.authorKim, Hee Jung-
dc.contributor.authorSong, Seok Bean-
dc.contributor.authorChoi, Jung Min-
dc.contributor.authorKim, Kyung Moon-
dc.contributor.authorCho, Baik Kee-
dc.contributor.authorCho, Dae Ho-
dc.contributor.authorPark, Hyun Jeong-
dc.date.available2021-02-22T13:48:30Z-
dc.date.created2020-09-03-
dc.date.issued2010-03-
dc.identifier.issn0022-202X-
dc.identifier.urihttps://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/13254-
dc.description.abstractExcessive 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.-
dc.language영어-
dc.language.isoen-
dc.publisherNATURE PUBLISHING GROUP-
dc.subjectGROWTH-FACTOR-BETA-
dc.subjectTRANSCRIPTION FACTOR ETS-1-
dc.subjectMATRIX GENE-EXPRESSION-
dc.subjectTGF-BETA-
dc.subjectSYSTEMIC-SCLEROSIS-
dc.subjectHEPATIC-FIBROSIS-
dc.subjectLIVER FIBROSIS-
dc.subjectENDOTHELIAL-CELLS-
dc.subjectSKIN FIBROBLASTS-
dc.subjectINTERFERON-ALPHA-
dc.titleIL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway-
dc.typeArticle-
dc.contributor.affiliatedAuthorCho, Dae Ho-
dc.identifier.doi10.1038/jid.2009.302-
dc.identifier.scopusid2-s2.0-76649097312-
dc.identifier.wosid000275017600014-
dc.identifier.bibliographicCitationJOURNAL OF INVESTIGATIVE DERMATOLOGY, v.130, no.3, pp.706 - 715-
dc.relation.isPartOfJOURNAL OF INVESTIGATIVE DERMATOLOGY-
dc.citation.titleJOURNAL OF INVESTIGATIVE DERMATOLOGY-
dc.citation.volume130-
dc.citation.number3-
dc.citation.startPage706-
dc.citation.endPage715-
dc.type.rimsART-
dc.type.docTypeArticle-
dc.description.journalClass1-
dc.description.journalRegisteredClassscie-
dc.description.journalRegisteredClassscopus-
dc.relation.journalResearchAreaDermatology-
dc.relation.journalWebOfScienceCategoryDermatology-
dc.subject.keywordPlusGROWTH-FACTOR-BETA-
dc.subject.keywordPlusTRANSCRIPTION FACTOR ETS-1-
dc.subject.keywordPlusMATRIX GENE-EXPRESSION-
dc.subject.keywordPlusTGF-BETA-
dc.subject.keywordPlusSYSTEMIC-SCLEROSIS-
dc.subject.keywordPlusHEPATIC-FIBROSIS-
dc.subject.keywordPlusLIVER FIBROSIS-
dc.subject.keywordPlusENDOTHELIAL-CELLS-
dc.subject.keywordPlusSKIN FIBROBLASTS-
dc.subject.keywordPlusINTERFERON-ALPHA-
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