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

@article{citeulike:6054101, 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.Journal of Investigative Dermatology advance online publication, 29 October 2009; doi:10.1038/jid.2009.302.}, author = {Kim, Hee Jung J. and Song, Seok Bean B. and Choi, Jung Min M. and Kim, Kyung Moon M. and Cho, Baik Kee K. and Cho, Dae Ho H. and Park, Hyun Jeong J.}, citeulike-article-id = {6054101}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/jid.2009.302}, citeulike-linkout-1 = {http://dx.doi.org/10.1038/jid2009302a}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19865096}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19865096}, day = {29}, doi = {10.1038/jid.2009.302}, issn = {1523-1747}, journal = {The Journal of investigative dermatology}, keywords = {il-18}, month = {October}, posted-at = {2009-11-01 22:29:47}, priority = {2}, publisher = {Nature Publishing Group}, title = {IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway.}, url = {http://dx.doi.org/10.1038/jid.2009.302}, year = {2009} }

TY - JOUR ID - citeulike:6054101 L3 - citeulike-article-id:6054101 N2 - 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.Journal of Investigative Dermatology advance online publication, 29 October 2009; doi:10.1038/jid.2009.302. JF - The Journal of investigative dermatology SN - 1523-1747 TI - IL-18 Downregulates Collagen Production in Human Dermal Fibroblasts via the ERK Pathway. PB - Nature Publishing Group KW - il-18 AU - Kim, Hee Jung AU - Song, Seok Bean AU - Choi, Jung Min AU - Kim, Kyung Moon AU - Cho, Baik Kee AU - Cho, Dae Ho AU - Park, Hyun Jeong PY - 2009/10/29/ UR - http://dx.doi.org/10.1038/jid.2009.302 ER -