Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation
Butyrate switches the pattern of chemokine secretion by intestinal epithelial cells through histone acetylation
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DOI：
10.1007/bf03402075
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发表时间：
1999-09-01
影响因子：
5.7
通讯作者：
Sanderson, IR
中科院分区：
文献类型：
--
作者：
Fusunyan, RD;Quinn, JJ;Sanderson, IR
背景资料：丁酸盐是肠道细菌的发酵产物，通过组蛋白乙酰化修饰染色质结构，从而改变基因转录。IL-8和MCP-1是肠上皮细胞表达的趋化因子，分别吸引中性粒细胞和单核细胞。材料和方法：采用ELISA和RNA转移印迹法检测肠上皮细胞IL-8和MCP-1的表达。乙酰化组蛋白在醋酸-尿素-Triton凝胶上分离。丁酸比较曲古抑菌素-A，组蛋白脱乙酰酶的特异性抑制剂和其他短链fatty acids.Results：Caco-2细胞组成型分泌MCP-1，但不IL-8。丁酸可逆地降低MCP-1的分泌。相反，丁酸盐增加IL-8的产生。丁酸盐和曲古抑菌素-A的作用在用IL-1 β刺激细胞时更大。丁酸盐和曲古抑菌素-A均增加组蛋白乙酰化。曲古抑菌素-A和其他乳木果链脂肪酸改变趋化因子的分泌，根据他们的影响组蛋白acetylation.Conclusions：丁酸可逆开关上皮细胞通过组蛋白乙酰化趋化因子的分泌。我们推测丁酸盐将常驻细菌的信息传递到上皮细胞。上皮细胞通过组蛋白乙酰化调节趋化因子的分泌来传递该信号。
Background: Butyrate, a fermentation product of intestinal bacteria, modifies chromatin structure through histone acetylation, thereby altering gene transcription. IL-8 and MCP-1 are chemokines, expressed by intestinal epithelial cells, which attract neutrophils and monocytes, respectively. We hypothesized that butyrate may alter IL-8 and MCP-1 expression by intestinal epithelial cells through histone acetylation.Materials and Methods: IL-8 and MCP-1 expression was measured by ELISA and RNA transfer blots. Acetylated histones were separated on acetic acid-urea-triton gels. Butyrate was compared to Trichostatin-A, a specific inhibitor of histone deacetylase and to other short chain fatty acids.Results: Caco-2 cells constitutively secreted MCP-1 but not IL-8. Butyrate reversibly decreased MCP-1 secretion. In contrast, butyrate increased IL-8 production. The effects of butyrate and Trichostatin-A were greater when cells were stimulated with IL-1 beta. Butyrate and Trichostatin-A both increased histone acetylation. Trichostatin-A and other shea chain fatty acids altered chemokine secretion according to their effect on histone acetylation.Conclusions: Butyrate reversibly switches chemokine secretion by epithelial cells through histone acetylation. We speculate that butyrate carries information from resident bacteria to epithelial cells. Epithelial cells transduce this signal through histone acetylation modulating the secretion of chemokines.