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Abstract：
Objective: Dermal fibroproliferative disorders impair patients\' quality of life. Although several therapeutic approaches exist for treatment of dermal scars, the development of effective ointments with few adverse effects could improve these therapeutic methods. Short-chain and ω-3 polyunsaturated fatty acids are reported to be immunomodulators with anti-inflammatory properties. Our aim was to evaluate anti-inflammatory and antifibrogenic effects of these fatty acids in human dermal fibroblasts. Methods: Cells were incubated with short-chain fatty acids (butyrate or propionate; 0-16 mM) and/or ω-3 polyunsaturated fatty acids (docosahexaenoic acid or eicosapentaenoic acid; 0-100 μM) for 24 hours to evaluate antifibrogenic effects and for 3 or 48 hours to evaluate anti-inflammatory effects after stimulation with lipopolysaccharide or without stimulation. Expression levels of α-smooth muscle actin, collagen I, collagen III, and IL-6 were evaluated, as were cell proliferation, stress fiber formation, and histone acetylation. Results: In the lipopolysaccharide-unstimulated group, butyrate inhibited mRNA expression of α-smooth muscle actin and collagen III more effectively than propionate and increased histone acetylation. Docosahexaenoic acid inhibited mRNA expression of α-smooth muscle actin and collagen III, whereas eicosapentaenoic acid did not. Combining butyrate with docosahexaenoic acid had stronger effects, downregulating α-smooth muscle actin, collagen I, and collagen III mRNA. As for cell proliferation and stress fiber formation, butyrate acted as a stronger inhibitor than docosahexaenoic acid and the combined administration had stronger effects. In the lipopolysaccharide-stimulated group, butyrate and docosahexaenoic acid attenuated IL-6 mRNA upregulation by lipopolysaccharide. Conclusion: Butyrate and docosahexaenoic acid may be a novel therapeutic approach to treatment of dermal fibroproliferative disorders.
摘要：
目的：皮肤纤维增生性疾病损害患者的生活质量。尽管存在几种治疗皮肤疤痕的治疗方法，开发副作用少的有效软膏可以改善这些治疗方法。据报道，短链和ω-3多不饱和脂肪酸是具有抗炎特性的免疫调节剂。我们的目的是评估这些脂肪酸在人真皮成纤维细胞中的抗炎和抗纤维化作用。方法：将细胞与短链脂肪酸（丁酸或丙酸盐；0-16mM）和/或ω-3多不饱和脂肪酸（二十二碳六烯酸或二十碳五烯酸；0-100μM）孵育24小时以评估抗纤维化作用，并孵育3或48小时以评估用脂多糖刺激或不刺激后的抗炎作用。α-平滑肌肌动蛋白的表达水平,胶原蛋白I，胶原蛋白III，和IL-6进行了评估，就像细胞增殖一样，应力纤维形成，和组蛋白乙酰化。结果：在未刺激的脂多糖组中，丁酸盐比丙酸盐更有效地抑制α-平滑肌肌动蛋白和胶原蛋白III的mRNA表达，并增加组蛋白乙酰化。二十二碳六烯酸抑制α-平滑肌肌动蛋白和胶原蛋白III的mRNA表达，而二十碳五烯酸没有。结合丁酸和二十二碳六烯酸有更强的效果，下调α-平滑肌肌动蛋白，胶原蛋白I，和胶原蛋白IIImRNA。至于细胞增殖和应力纤维形成，丁酸酯是比二十二碳六烯酸更强的抑制剂，联合给药具有更强的作用。在脂多糖刺激组中，丁酸盐和二十二碳六烯酸减弱了脂多糖对IL-6mRNA的上调。结论：丁酸酯和二十二碳六烯酸可能是治疗真皮纤维增生性疾病的一种新方法。
