The mechanism involved in the inhibitory action of tranilast on collagen biosynthesis of keloid fibroblasts.
Tranilast, an anti-allergic drug inhibiting the release of substances such as histamine and prostaglandins from mast cells, was previously reported to suppress collagen synthesis of fibroblasts derived from keloid tissues. However, the inhibitory mechanism on collagen synthesis is unknown. We studied its inhibitory mechanism on collagen synthesis by culturing fibroblasts from keloid and hypertrophic scar tissues of humans. Collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue is greater than that from healthy human skin. Tranilast (3-100 microM) did not inhibit prolyl hydroxylase (the rate-limiting enzyme in collagen synthesis) activity. Tranilast (3-300 microM) suppressed the collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue but not healthy skin fibroblasts. Tranilast (30-300 microM) inhibited the release of transforming growth factor (TGF)-beta 1 from keloid fibroblasts, which enhances the collagen synthesis of keloid fibroblasts. Anti-TGF-beta 1 antibody (50 microliter/ml) inhibited the collagen synthesis, although diphenhydramine (10 microM) and indomethacin (10 microM) did not show any inhibition. These results suggest that tranilast inhibits collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue through suppressing the release of TGF-beta 1 from the fibroblasts themselves.
D002921:Cicatrix / Q000378:metabolism; D003094:Collagen / Q000096:biosynthesis*; D003864:Depression, Chemical; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D006634:Histamine H1 Antagonists; D016212:Transforming Growth Factor beta; D062367:ortho-Aminobenzoates; D003094:Collagen; D011393:Procollagen-Proline Dioxygenase; C012293:tranilast