PMID- 11178980 OWN - NLM STAT- MEDLINE DCOM- 20010405 LR - 20101118 IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 281 IP - 1 DP - 2001 Feb 16 TI - Effect of interleukin-10 on the gene expression of type I collagen, fibronectin, and decorin in human skin fibroblasts: differential regulation by transforming growth factor-beta and monocyte chemoattractant protein-1. PG - 200-5 AB - Interleukin-10 (IL-10) is a cytokine with many regulatory functions. In particular, IL-10 exerts neutralizing effect on other cytokines, and therefore IL-10 is thought to have important therapeutic implications. Recent reports suggest that IL-10 regulates not only immunocytes but also collagen and collagenase gene expression in fibroblasts. In this study, we investigated the effect of IL-10 on gene expression of extracellular matrix (ECM) proteins, such as type I collagen, fibronectin, and decorin, in human skin fibroblasts. Results of Northern blot analysis showed that both collagen I and fibronectin mRNAs were downregulated, while decorin gene expression was enhanced by IL-10 (10 ng/ml) time-dependently (6-24 h). alpha1(I) collagen and fibronectin mRNAs were decreased to one-third and one-fourth, respectively, by 50 ng/ml IL-10, whereas decorin mRNA was increased up to 2.7-fold by 50 ng/ml IL-10. Response to IL-10 by scleroderma fibroblasts was similar to that in normal dermal fibroblasts, with decreased expression levels of collagen and fibronectin and induced decorin mRNA levels. Transforming growth factor-beta (TGF-beta) is a crucial fibrogenic cytokine which upregulates the mRNA expression of collagen and fibronectin, whereas it downregulates decorin mRNA expression in fibroblasts. Monocyte chemoattractant protein-1 (MCP-1) has recently been shown to upregulate the type I collagen mRNA expression in cultured fibroblasts. We therefore examined whether IL-10 alters gene expression of ECM elicited by TGF-beta and MCP-1. Our results demonstrated that IL-10 downregulated the TGF-beta-elicited increase of mRNA expression of type I collagen and fibronectin, while partially recovering TGF-beta-elicited decrease of decorin expression in normal skin fibroblasts. By contrast, IL-10 did not alter the MCP-1-elicited upregulation of mRNA expression of either alpha1(I) collagen and decorin. Our data indicate that IL-10 differentially regulates TGF-beta and MCP-1 in the modulation of ECM proteins and therefore suggest that IL-10 plays a role in the regulation of tissue remodeling. FAU - Yamamoto, T AU - Yamamoto T AD - Department of Dermatology, University of Cologne, Joseph-Stelzmann Strasse 9, Cologne, 50924, Germany. yamamoto.derm@med.tmd.ac.jp FAU - Eckes, B AU - Eckes B FAU - Krieg, T AU - Krieg T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Chemokine CCL2) RN - 0 (DCN protein, human) RN - 0 (Decorin) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Fibronectins) RN - 0 (Proteoglycans) RN - 0 (RNA, Messenger) RN - 0 (Transforming Growth Factor beta) RN - 130068-27-8 (Interleukin-10) RN - 9007-34-5 (Collagen) SB - IM MH - Blotting, Northern MH - Cells, Cultured MH - Chemokine CCL2/*metabolism MH - Collagen/*biosynthesis MH - Decorin MH - Dose-Response Relationship, Drug MH - Down-Regulation MH - Extracellular Matrix/metabolism MH - Extracellular Matrix Proteins MH - Fibroblasts/*metabolism MH - Fibronectins/*biosynthesis MH - Gene Expression Regulation/*drug effects MH - Humans MH - Interleukin-10/*pharmacology MH - Proteoglycans/*biosynthesis MH - RNA, Messenger/metabolism MH - Scleroderma, Localized/metabolism MH - Skin/*metabolism MH - Time Factors MH - Transforming Growth Factor beta/*metabolism MH - Up-Regulation EDAT- 2001/02/17 11:00 MHDA- 2001/04/06 10:01 CRDT- 2001/02/17 11:00 PHST- 2001/02/17 11:00 [pubmed] PHST- 2001/04/06 10:01 [medline] PHST- 2001/02/17 11:00 [entrez] AID - S0006-291X(01)94321-9 [pii] AID - 10.1006/bbrc.2001.4321 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2001 Feb 16;281(1):200-5. doi: 10.1006/bbrc.2001.4321.