Macrophage inflammatory protein-2: Chromosomal regulation in rat small intestinal epithelial cells
Macrophage inflammatory protein-2: Chromosomal regulation in rat small intestinal epithelial cells
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DOI：
10.1073/pnas.94.19.10279
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发表时间：
1997-09-16
影响因子：
11.1
通讯作者：
Sanderson, IR
中科院分区：
文献类型：
--
作者：
Ohno, Y;Lee, J;Sanderson, IR
非致病性常驻细菌参与小肠炎症的发病机制，但这些细菌产生的分子信息尚不清楚，炎症反应涉及特异性白细胞亚群的募集。因此，我们假设丁酸盐，一种正常的细菌代谢物，可能通过放大上皮细胞对促炎信号的反应来调节上皮细胞的趋化因子分泌。我们研究了趋化因子巨噬细胞炎症蛋白-2 （MIP-2）在大鼠小肠上皮细胞系IEC-6中的表达。用脂多糖或白细胞介素1 β (IL-1 β)刺激细胞，用丁酸钠孵育，用PAGE检测Triton X乙酸-尿素凝胶中组蛋白的乙酰化。未刺激的IEC-6细胞不分泌MIP-2，但脂多糖和IL-1 β诱导了MIP-2的表达，丁酸盐增强了MIP-2在脂多糖刺激和IL-1 β刺激肠细胞中的分泌；而单用丁酸盐对MIP-2的表达无诱导作用。丁酸增加了从IEC-6细胞细胞核中提取的组蛋白的乙酰化，此外，组蛋白的乙酰化（由组蛋白去乙酰化酶的特异性抑制剂trichostatin A诱导）增强了IL-1 β刺激细胞的MIP-2表达。综上所述，trichostatin A复制了丁酸盐对MIP-2分泌的影响，因此，丁酸盐通过增加组蛋白乙酰化来增加受刺激细胞的MIP-2分泌。我们推测丁酸盐将信息从细菌传递到上皮细胞。上皮细胞通过组蛋白去乙酰化酶转导该信号，调节趋化因子的分泌。
Nonpathogenic, resident bacteria participate in the pathogenesis of inflammation in the small intestine, but the molecular messages produced by such bacteria are unknown, Inflammatory responses involve the recruitment of specific leukocyte subsets. We, therefore, hypothesized that butyrate, a normal bacterial metabolite, may modulate chemokine secretion by epithelial cells, by amplifying their response to proinflammatory signals. We studied the expression of the chemokine, macrophage inflammatory protein-2 (MIP-2) by the rat small intestinal epithelial cell line, IEC-6. Cells were stimulated with lipopolysaccharide or with interleukin 1 beta (IL-1 beta) and incubated with sodium butyrate, Acetylation of histones was examined in Triton X acetic acid-urea gels by PAGE. Unstimulated IEC-6 cells did not secrete MIP-2, However, lipopolysaccharide and IL-1 beta induced MIP-2 expression, Butyrate enhanced MIP-2 secretion both in lipopolysaccharide-stimulated and IL-1 beta-stimulated enterocytes; but butyrate alone did not induce MIP-2 expression. Butyrate increased the acetylation of histones extracted from the nuclei of IEC-6 cells, Furthermore, acetylation of histones (induced by trichostatin A, a specific inhibitor of histone deacetylase) enhanced MIP-2 expression by cells stimulated with IL-1 beta. In conclusion, trichostatin A reproduced the effects of butyrate on MIP-2 secretion, Butyrate, therefore, increases MIP-2 secretion in stimulated cells by increasing histone acetylation. We speculate that butyrate carries information from bacteria to epithelial cells. Epithelial cells transduce this signal through histone deacetylase, modulating the secretion of chemokines.