Yi Dan, Bihl Ji, Newman Mackenzie S, Chen Yanfang, Simman Richard
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA.
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA ; Department of Plastic and Reconstructive Surgery, Boonshoft School of Medicine, Wright State University, 3640 Colonel Glenn Hwy, Dayton, OH 45435, USA.
Dermatol Res Pract. 2014;2014:736957. doi: 10.1155/2014/736957. Epub 2014 Sep 22.
Keloid scarring is a fibroproliferative disorder due to the accumulation of collagen type I. Tolfenamic acid (TA), a nonsteroidal anti-inflammatory drug, has been found to potentially affect the synthesis of collagen in rats. In this preliminary study, we aimed to test the effects of TA on cell proliferation, cell apoptosis, and the deposition of intracellular collagen in keloid fibroblasts. Normal fibroblasts (NFs) and keloid fibroblasts (KFs) were obtained from human dermis tissue. Within the dose range 10(-3)-10(-6) M and exposure times 24 h, 48 h, and 72 h, we found that 0.55 × 10(-3) M TA at 48 h exposure exhibited significantly decreased cell proliferation in both NFs and KFs. Under these experimental conditions, we demonstrated that (1) TA treatment induced a remarkable apoptotic rate in KFs compared to NFs; (2) TA treatment reduced collagen production in KFs versus NFs; (3) TA treatment decreased collagen type I expression in KFs comparing to that of NFs. In summary, our data suggest that TA decreases cell proliferation, induces cell apoptosis, and inhibits collagen accumulation in KFs.
瘢痕疙瘩是一种由于I型胶原蛋白积聚引起的纤维增生性疾病。托芬那酸(TA)是一种非甾体抗炎药,已发现其可能影响大鼠体内胶原蛋白的合成。在这项初步研究中,我们旨在测试TA对瘢痕疙瘩成纤维细胞的细胞增殖、细胞凋亡和细胞内胶原蛋白沉积的影响。正常成纤维细胞(NFs)和瘢痕疙瘩成纤维细胞(KFs)取自人真皮组织。在10(-3)-10(-6) M的剂量范围内以及24 h、48 h和72 h的暴露时间下,我们发现48 h暴露时0.55×10(-3) M的TA在NFs和KFs中均表现出细胞增殖显著降低。在这些实验条件下,我们证明:(1)与NFs相比,TA处理诱导KFs出现显著的凋亡率;(2)与NFs相比,TA处理降低了KFs中的胶原蛋白产生;(3)与NFs相比,TA处理降低了KFs中I型胶原蛋白的表达。总之,我们的数据表明TA可降低KFs中的细胞增殖、诱导细胞凋亡并抑制胶原蛋白积聚。