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

Interleukin-10 (IL-10) is a cytokine with many regulatory functions. In par ticular, IL-10 exerts neutralizing effect on other cytokines, and therefore IL-10 is thought to have important therapeutic implications. Recent report s suggest that IL-10 regulates nest 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) protei ns, such as type I collagen, fibronectin, and decorin, in human skin fibrob lasts. Results of Northern blot analysis showed that both collagen I and fi bronectin mRNAs were downregulated, while decorin gene expression was enhan ced by IL-10 (10 ng/ml) time-dependently (6-24 h). alpha1(I) collagen and f ibronectin mRNAs mere 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 th at in normal dermal fibroblasts, with decreased expression levels of collag en and fibronectin and induced decorin mRNA levels. Transforming growth fac tor-beta (TGF-beta) is a crucial fibrogenic cytokine which upregulates the mRNA expression of collagen and fibronectin, whereas it down-regulates deco rin mRNA expression its fibroblasts. Monocyte chemoattractant protein-1 (MC P-1) has recently been shown to upregulate the type I collagen mRNA express ion in cultured fibroblasts. We therefore examined whether IL-10 alters gen e expression of ECM elicited by TGF-beta and MCP-1. Our results demonstrate d that IL-10 downregulated the TGF-beta -elicited increase of mRNA expressi on of type I collagen and fibronectin, while partially recovering TGF-beta -elicited decrease of decorin expression in normal skin fibroblasts. By con trast, IL-10 did not alter the MCP-1-elicited upregulation of mRNA expressi on of either alpha1(I) collagen and decorin. Our data indicate that IL-10 d ifferentially regulates TGF-beta and MCP-1 in the modulation of ECM protein s and therefore suggest that IL-10 plays a role in the regulation of tissue remodeling. (C) 2001 Academic Press.