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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kim, Hee Jung Song, Seok Bean Choi, Jung Min Kim, Kyung Moon Cho, Baik Kee Cho, Dae Ho Park, Hyun Jeong |
| Description | Author Affiliation: Kim HJ ( Department of Dermatology, St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.) |
| 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. |
| File Format | HTM / HTML |
| ISSN | 0022202X |
| e-ISSN | 15231747 |
| Journal | Journal of Investigative Dermatology |
| Issue Number | 3 |
| Volume Number | 130 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2010-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Discipline Dermatology Collagen Type I Metabolism Dermis Cytology Extracellular Signal-regulated Map Kinases Fibroblasts Interleukin-18 Scleroderma, Systemic Cells, Cultured Collagen Genetics Collagen Type Iii Down-regulation Drug Effects Physiology Enzyme Inhibitors Pharmacology Antagonists & Inhibitors Flavonoids Gene Expression Map Kinase Signaling System Promoter Regions, Genetic Proto-oncogene Protein C-ets-1 Rna, Small Interfering Physiopathology Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Biochemistry Molecular Biology Dermatology |
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