Maeshige Noriaki, Torii Kazuhiro, Tabuchi Hiroto, Imai Midori, Koga Yuka, Uemura Mikiko, Aoyama-Ishikawa Michiko, Miyoshi Makoto, Fujino Hidemi, Terashi Hiroto, Usami Makoto
Department of Rehabilitation Science.
Division of Nutrition and Metabolism, Department of Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Japan.
Eplasty. 2019 Mar 1;19:e4. eCollection 2019.
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. 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. 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. Butyrate and docosahexaenoic acid may be a novel therapeutic approach to treatment of dermal fibroproliferative disorders.
皮肤纤维增生性疾病会损害患者的生活质量。尽管目前有多种治疗皮肤瘢痕的方法，但开发出不良反应少的有效药膏可以改进这些治疗手段。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对人皮肤成纤维细胞的抗炎和抗纤维化作用。将细胞与短链脂肪酸（丁酸盐或丙酸盐；0 - 16 mM）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 - 100 μM）孵育24小时以评估抗纤维化作用，孵育3小时或48小时以评估在脂多糖刺激或未刺激后的抗炎作用。评估α-平滑肌肌动蛋白、胶原蛋白I、胶原蛋白III和白细胞介素-6的表达水平，以及细胞增殖、应力纤维形成和组蛋白乙酰化情况。在未用脂多糖刺激的组中，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，而二十碳五烯酸则没有。丁酸盐与二十二碳六烯酸联合使用效果更强，可下调α-平滑肌肌动蛋白、胶原蛋白I和胶原蛋白III的mRNA。至于细胞增殖和应力纤维形成，丁酸盐比二十二碳六烯酸是更强的抑制剂，联合给药效果更强。在脂多糖刺激的组中，丁酸盐和二十二碳六烯酸减弱了脂多糖引起的白细胞介素-6 mRNA上调。丁酸盐和二十二碳六烯酸可能是治疗皮肤纤维增生性疾病的一种新的治疗方法。
