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 with regulatory functions on a number of interleukins. In this study we show that recombinant human IL-10 affects the expression of several genes 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 stromelysin gene expression were markedly enhanced by IL-10. No effect on tissue inhibitor of metalloproteases mRNA levels was noted. Transient transfections of skin fibroblasts with type I collagen promoter/chloramphenicol acetyl transferase reporter gene constructs showed downregulation by IL-10, suggesting inhibition at the transcriptional level. When compared with control cultures, incubation with IL-10 resulted in a decrease in immunostaining of fibroblast cultures with antibodies to human type I collagen. In contrast, immunostaining of such IL-10-treated cultures with antibodies to human collagenase resulted in an increase in immunostaining. This study suggests a role for IL-10 in the breakdown and remodeling of the extracellular matrix.
Reitamo
S
S
Department of Dermatology, Jefferson Medical College, Philadelphia, Pennsylvania 19107.
Remitz
A
A
Tamai
K
K
Uitto
J
J
D015152:Blotting, Northern; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000235:genetics; D017364:Collagenases / Q000096:biosynthesis / Q000235:genetics; D003238:Connective Tissue / Q000378:metabolism; D003239:Connective Tissue Cells; D015536:Down-Regulation / Q000187:drug effects; D005109:Extracellular Matrix / Q000201:enzymology / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology*; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D012333:RNA, Messenger; D016753:Interleukin-10; D003094:Collagen; D017364:Collagenases; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3