Inhibitory Effects of Short-Chain Fatty Acids on Matrix Metalloproteinase Secretion from Human Colonic Subepithelial Myofibroblasts
Inhibitory Effects of Short-Chain Fatty Acids on Matrix Metalloproteinase Secretion from Human Colonic Subepithelial Myofibroblasts
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DOI：
10.1007/s10620-008-0348-1
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发表时间：
2009-02-01
影响因子：
3.1
通讯作者：
Fujiyama, Yoshihide
中科院分区：
文献类型：
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作者：
Kawamura, Takato;Andoh, Akira;Fujiyama, Yoshihide
背景和目的短链脂肪酸（SCFA），例如乙酸盐、丙酸盐和丁酸盐，是结肠中膳食纤维细菌发酵的主要副产物。在本报告中，我们研究了 SCFA 如何调节人结肠上皮下肌成纤维细胞 (SEMF) 分泌基质金属蛋白酶 (MMP)。材料和方法 SEMF 通过α-平滑肌肌动蛋白和波形蛋白的表达进行鉴定。通过酶联免疫吸附测定测定细胞因子诱导的 MMP-1 和 MMP-3 水平。通过RT-PCR和实时PCR方法分析细胞因子诱导的MMP mRNA表达。结果醋酸对MMP的分泌没有影响。丙酸盐和丁酸盐显着减弱 IL-1β 和 TNF-α 诱导的 MMP-1 和 MMP-3 分泌。在 mRNA 水平上也观察到类似的反应。丙酸盐和丁酸盐不会调节 IL-1 β 和 TNF-α 诱导的丝裂原激活蛋白激酶 (MAPK) 的激活，而 MAPK 在 MMP 诱导中起着至关重要的作用。 Trichostatin A 是一种组蛋白脱乙酰酶抑制剂，可减少 IL-1β 诱导的 MMP-1 和 MMP-3 mRNA 表达，并抑制 TNF-α 诱导的 MMP-3 mRNA 表达。结论 SCFAs通过抑制结肠MMP分泌发挥抗炎作用。 SCFA 对 MMP 分泌的抑制作用可能与其组蛋白过度乙酰化作用有关。
Background and Aims Short-chain fatty acids (SCFAs), such as acetate, propionate and butyrate, are the major by-product of bacterial fermentation of dietary fiber in the colon. In this report, we investigated how SCFAs modulate matrix metalloproteinase (MMP) secretion from human colonic subepithelial myofibroblasts (SEMFs). Materials and Methods SEMFs were identified by expression of alpha-smooth muscle actin and vimentin. Cytokine-induced MMP-1 and MMP-3 levels were determined by enzyme-linked immunosorbent assay. Cytokine-induced MMP mRNA expression was analyzed by RT-PCR and real-time PCR methods. Results Acetate had no effect on MMP secretion. Propionate and butyrate significantly attenuated IL-1 beta- and TNF-alpha-induced MMP-1 and MMP-3 secretion. Similar responses were also observed at the mRNA levels. Propionate and butyrate did not modulate IL-1 beta- and TNF-alpha-induced activation of mitogen-activated protein kinases (MAPKs), which play a crucial role in MMP induction. Trichostatin A, a histone-deacetylase inhibitor, reduced IL-1 beta-induced MMP-1 and MMP-3 mRNA expression, and suppressed TNF-alpha-induced MMP-3 mRNA expression. Conclusion SCFAs play an anti-inflammatory role through suppression of MMP secretion in the colon. Inhibitory effects of SCFAs on MMP secretion might be associated with their action of histone hyperacetylation.