The Mechanism Involved in the Inhibitory Action of Tranilast on Collagen Biosynthesis of Keloid Fibroblasts

The Japanese Journal of Pharmacology

Akihide Koda¹  Shinji Kikuchi²  Haruo Suzawa²  Nobuhiko Arai² 

[1] Department of Pharmacology, Gifu Pharmaceutical University;Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd.

关键词: Tranilast;    Collagen synthesis;    Keloid fibroblast;    Transforming growth factor (TGF)-β1;    Cytokine;   

DOI  :  10.1254/jjp.60.91

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(27)Cited-By(95)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 μM) did not inhibit prolyl hydroxylase (the rate-limiting enzyme in collagen synthesis) activity. Tranilast (3-300 μM) suppressed the collagen synthesis of fibroblasts from keloid and hypertrophic scar tissue but not healthy skin fibroblasts. Tranilast (30-300 μM) inhibited the release of transforming growth factor (TGF)-β1 from keloid fibroblasts, which enhances the collagen synthesis of keloid fibroblasts. Anti-TGF-β1 antibody (50 μl/ml) inhibited the collagen synthesis, although diphenhydramine (10 μM) and indomethacin (10 μM) 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-β1 from the fibroblasts themselves.

【 授权许可】

Unknown