INTERLEUKIN-10 MODULATES TYPE-I COLLAGEN AND MATRIX METALLOPROTEASE GENE-EXPRESSION IN CULTURED HUMAN SKIN FIBROBLASTS

IL-10, originally isolated from mouse helper T cells, is a cytokine wi th regulatory functions on a number of interleukins. In this study we show that recombinant human IL-10 affects the expression of several ge nes involved in extracellular matrix synthesis and remodeling in human dermal fibroblast cultures. As judged by Northern blot analyses, type I collagen gene expression was downregulated, while collagenase and s tromelysin gene expression were markedly enhanced by IL-10. No effect on tissue inhibitor of metalloproteases mRNA levels was noted. Transie nt transfections of skin fibroblasts with type I collagen promoter/chl oramphenicol acetyl transferase reporter gene constructs showed downre gulation by IL-10, suggesting inhibition at the transcriptional level. When compared with control cultures, incubation with IL-10 resulted i n a decrease in immunostaining of fibroblast cultures with antibodies to human type I collagen. In contrast, immunostaining of such IL-10-tr eated cultures with antibodies to human collagenase resulted in an inc rease in immunostaining. This study suggests a role for IL-10 in the b reakdown and remodeling of the extracellular matrix.