Suzawa H, Kikuchi S, Arai N, Koda A
Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Jpn J Pharmacol. 1992 Oct;60(2):91-6. doi: 10.1254/jjp.60.91.
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.
曲尼司特是一种抗过敏药物，可抑制肥大细胞释放组胺和前列腺素等物质，此前有报道称其可抑制瘢痕疙瘩组织来源的成纤维细胞的胶原蛋白合成。然而，其对胶原蛋白合成的抑制机制尚不清楚。我们通过培养人瘢痕疙瘩和增生性瘢痕组织中的成纤维细胞，研究了其对胶原蛋白合成的抑制机制。瘢痕疙瘩和增生性瘢痕组织中的成纤维细胞的胶原蛋白合成量大于健康人皮肤中的成纤维细胞。曲尼司特（3 - 100微摩尔）不抑制脯氨酰羟化酶（胶原蛋白合成中的限速酶）的活性。曲尼司特（3 - 300微摩尔）可抑制瘢痕疙瘩和增生性瘢痕组织中的成纤维细胞的胶原蛋白合成，但对健康皮肤成纤维细胞无此作用。曲尼司特（30 - 300微摩尔）可抑制瘢痕疙瘩成纤维细胞中转化生长因子（TGF）-β1的释放，而TGF-β1可增强瘢痕疙瘩成纤维细胞的胶原蛋白合成。抗TGF-β1抗体（50微升/毫升）可抑制胶原蛋白合成，而苯海拉明（10微摩尔）和吲哚美辛（10微摩尔）未显示出任何抑制作用。这些结果表明，曲尼司特通过抑制成纤维细胞自身TGF-β1的释放来抑制瘢痕疙瘩和增生性瘢痕组织中的成纤维细胞的胶原蛋白合成。
