Suzawa H, Kikuchi S, Ichikawa K, Koda A
Pharmacological Laboratories, Kissei Pharmaceutical Co., Ltd., Nagano, Japan.
Jpn J Pharmacol. 1992 Oct;60(2):85-90. doi: 10.1254/jjp.60.85.
Tranilast, an anti-allergic drug that inhibits the release of substances such as histamine and prostaglandins from mast cells, has been reported to improve keloids and hypertrophic scars which originate from the abnormal proliferation and excessive collagen accumulation of fibroblasts. It has been considered that various chemical mediators produced by inflammatory cells play important roles in the development of keloids and hypertrophic scars. We therefore studied the effect of tranilast on the release of chemical mediators including transforming growth factor (TGF)-beta 1, interleukin (IL)-1 beta and prostaglandin (PG) E2 which are produced by the human monocytes-macrophages, and estimated whether these mediators induce collagen synthesis and cell proliferation of normal skin fibroblasts. Tranilast inhibited the release of TGF-beta 1, IL-1 beta and PGE2 from the human monocytes-macrophages. TGF-beta 1 (25-200 pM) enhanced the collagen synthesis by fibroblasts. IL-1 (0.1-1 U/ml) increased the proliferation and conversely decreased the collagen synthesis. PGE2 (2 micrograms/ml) enhanced the collagen synthesis. These results suggest that tranilast suppresses collagen synthesis by fibroblasts through inhibiting TGF-beta 1 and PGE2 production and cell proliferation by fibroblasts through inhibiting IL-1 production by inflammatory cells such as macrophages.
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，据报道它能改善瘢痕疙瘩和增生性瘢痕，这些瘢痕源于成纤维细胞的异常增殖和过度胶原积累。人们认为炎症细胞产生的各种化学介质在瘢痕疙瘩和增生性瘢痕的形成中起重要作用。因此，我们研究了曲尼司特对人单核细胞 - 巨噬细胞产生的包括转化生长因子（TGF）-β1、白细胞介素（IL）-1β和前列腺素（PG）E2在内的化学介质释放的影响，并评估这些介质是否诱导正常皮肤成纤维细胞的胶原合成和细胞增殖。曲尼司特抑制人单核细胞 - 巨噬细胞释放TGF-β1、IL-1β和PGE2。TGF-β1（25 - 200 pM）增强成纤维细胞的胶原合成。IL-1（0.1 - 1 U/ml）增加细胞增殖，反之则减少胶原合成。PGE2（2微克/毫升）增强胶原合成。这些结果表明，曲尼司特通过抑制TGF-β1和PGE2的产生来抑制成纤维细胞的胶原合成，并通过抑制巨噬细胞等炎症细胞产生IL-1来抑制成纤维细胞的细胞增殖。
