Short-chain fatty acids alter tight junction permeability in intestinal monolayer cells via lipoxygenase activation
Short-chain fatty acids alter tight junction permeability in intestinal monolayer cells via lipoxygenase activation
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DOI：
10.1016/j.nut.2004.12.004
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发表时间：
2005-07-01
期刊：
影响因子：
4.4
通讯作者：
Miyoshi, M
中科院分区：
文献类型：
--
作者：
Ohata, A;Usami, M;Miyoshi, M
目的：脂氧合酶(LOX)和环氧合酶(COX)参与丁酸诱导的细胞分化或凋亡，但对紧密连接(TJ)通透性的影响尚未见报道。丁酸和丙酸的一个主要活性是通过组蛋白去乙酰化组蛋白去乙酰酶抑制活性来调节基因转录。本研究通过组蛋白乙酰化研究了短链脂肪酸、丁酸、丙酸和醋酸盐对肠道单层细胞TJ通透性改变中LOX和COX的激活作用及其可能的机制。方法：采用Transwell小室观察LOX和COX抑制剂对短链脂肪酸诱导的Caco-2细胞TJ通透性的影响。此外，还评价了羟二十碳四烯酸(LOX的产物)对TJ通透性的影响。结果：LOX抑制剂可明显抑制丁酸盐对TJ通透性的影响，而COX抑制剂则无此作用。熏鲑鱼和。COX抑制剂可部分抑制丙酸的作用，但不能抑制醋酸盐的作用。结论：短链脂肪酸，尤其是丁酸，通过组蛋白乙酰化激活LOX，诱导TJ通透性改变。(C)2005 Elsevier Inc.保留所有权利。
Objective: Involvement of lipoxygenase (LOX) and cyclo-oxygenase (COX) on cellular differentiation or apoptosis induced by butyrate has been reported recently, but the effect on tight junction (TJ) permeability has not been reported. One major activity of butyrate and, to a lesser extent, propionate is to modulate gene transcription via histone acetylation by their histone deacetylase inhibitor activity. In this study, we evaluated the activation of LOX and COX in TJ permeability changes by short-chain fatty acids, butyrate, propionate, and acetate in intestinal monolayer cells and their possible mechanism by histone acetylation.Methods: The effects of LOX and COX inhibitors on TJ permeability and the expression of LOX or COX mRNA induced by short-chain fatty acids were investigated in Caco-2 cells using Transwell chambers. The effects of hydroxyeicosatetraenoic acid (a product of LOX) on TJ permeability were also evaluated. The effects of short-chain fatty acids were compared with those of trichostatin A (histone deacetylase inhibitor).Results: A LOX inhibitor clearly inhibited the effect of butyrate on TJ permeability, whereas COX inhibitors did not. The LOX and. COX inhibitors partly inhibited the effects of propionate, but not of acetate. Butyrate increased LOX mRNA expression, and hydroxyeicosatetraenoic acid and trichostatin A mimicked its effect.Conclusion: These results suggest that short-chain fatty acids, especially butyrate, induce TJ permeability changes through LOX activation through histone acetylation. (c) 2005 Elsevier Inc. All rights reserved.