Interferon-alpha and interferon-gamma reduce excessive collagen synthesis and procollagen mRNA levels of scleroderma fibroblasts in culture.
The effects of interferon-alpha and interferon-gamma on collagen synthesis and mRNA levels of type I and type III procollagens were studied in skin fibroblasts cultured from affected and unaffected skin sites of two patients with localized scleroderma (morphea). Both scleroderma cell lines exhibited elevated type I and type III procollagen mRNA levels to account for the increased procollagen synthesis, when compared to the unaffected controls. Interferon-gamma treatment resulted in a dose-dependent reduction in collagen synthesis and procollagen mRNA levels in scleroderma fibroblasts. A 72-h exposure to interferon-gamma reduced procollagen mRNA levels in the scleroderma fibroblast lines to the levels exhibited by the unaffected control fibroblasts. The suppressive effect of interferon-alpha on procollagen mRNA levels was somewhat weaker than that of interferon-gamma. The results suggest potential use of interferon-gamma in treatment and prevention of human fibrotic conditions.
D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D006909:Hydroxyproline / Q000378:metabolism; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011347:Procollagen / Q000235:genetics*; D011392:Proline / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics*; D012594:Scleroderma, Localized / Q000378:metabolism*; D012867:Skin / Q000378:metabolism*
D007370:Interferon Type I; D011347:Procollagen; D012333:RNA, Messenger; D007371:Interferon-gamma; D003094:Collagen; D011392:Proline; D006909:Hydroxyproline