Redirection of Epithelial Immune Responses by Short-Chain Fatty Acids through Inhibition of Histone Deacetylases.
Redirection of Epithelial Immune Responses by Short-Chain Fatty Acids through Inhibition of Histone Deacetylases.
复制标题
通过抑制组蛋白脱乙酰基酶，短链脂肪酸通过短链脂肪酸重定向。
DOI：
10.3389/fimmu.2015.00554
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发表时间：
2015
影响因子：
7.3
通讯作者：
Strijbis K
中科院分区：
文献类型：
--
作者：
Lin MY;de Zoete MR;van Putten JP;Strijbis K
短链脂肪酸（SCFA）是微生物发酵的产物，对肠道上皮健康很重要。在这里，我们描述了SCFAs对上皮细胞中的Toll样受体（TLR）反应具有快速和可逆的作用。将HEK 293或HeLa上皮细胞与生理浓度的SCFA丁酸盐或丙酸盐一起孵育增强了由TLR 5、TLR 2/1、TLR 4和TLR 9激动剂诱导的NF-κB活化。SCFAs还增加了NF-κB对肿瘤坏死因子α（TNFα）的激活。HT-29结肠上皮细胞的比较转录分析显示，SCFA增强了TLR 5诱导的TNFα转录，但抑制甚至消除了TLR 5介导的IL-8和单核细胞趋化蛋白1的诱导。SCFA是已知的组蛋白脱乙酰酶（HDAC）抑制剂。丁酸盐或丙酸盐引起上皮细胞中组蛋白乙酰化的快速增加，类似于小分子HDAC抑制剂阿司他丁A（TSA）。TSA还模拟SCFA对TLR-NF-κB应答的作用。这项研究表明，细菌SCFA迅速改变宿主细胞的表观遗传状态，导致先天免疫应答的重定向和细胞因子/趋化因子表达的选择性重编程。
Short-chain fatty acids (SCFAs) are products of microbial fermentation that are important for intestinal epithelial health. Here, we describe that SCFAs have rapid and reversible effects on toll-like receptor (TLR) responses in epithelial cells. Incubation of HEK293 or HeLa epithelial cells with the SCFAs butyrate or propionate at physiological concentrations enhanced NF-κB activation induced by TLR5, TLR2/1, TLR4, and TLR9 agonists. NF-κB activation in response to tumor necrosis factor α (TNFα) was also increased by SCFAs. Comparative transcript analysis of HT-29 colon epithelial cells revealed that SCFAs enhanced TLR5-induced transcription of TNFα but dampened or even abolished the TLR5-mediated induction of IL-8 and monocyte chemotactic protein 1. SCFAs are known inhibitors of histone deacetylases (HDACs). Butyrate or propionate caused a rapid increase in histone acetylation in epithelial cells, similar to the small molecule HDAC inhibitor trichostatin A (TSA). TSA also mimicked the effects of SCFAs on TLR–NF-κB responses. This study shows that bacterial SCFAs rapidly alter the epigenetic state of host cells resulting in redirection of the innate immune response and selective reprograming of cytokine/chemokine expression.