Butyrate modulates intestinal epithelial cell-mediated neutrophil migration
Butyrate modulates intestinal epithelial cell-mediated neutrophil migration
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DOI：
10.1046/j.1365-2249.2003.02056.x
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发表时间：
2003-01-01
影响因子：
4.6
通讯作者：
Singer, MV
中科院分区：
文献类型：
--
作者：
Böcker, U;Nebe, T;Singer, MV
丁酸是一种由结肠细菌释放的短链脂肪酸，用于治疗炎症性肠病，具有免疫调节作用。本研究的目的是确定丁酸盐暴露对人肠上皮细胞（IEC）促炎反应的功能后果。通过转染荧光素酶构建体测定用丁酸盐预处理然后暴露于促炎刺激物的IEC中的IL-8启动子活性。通过ELISA测定IL-8分泌，通过流式细胞术测定中性粒细胞迁移。用逆转录聚合酶链反应（RT-PCR）检测受体mRNA。丁酸在转录水平上调节Caco-2和HT-29细胞中促炎性IL-8的分泌差异。提示IL-1 β刺激HT-29细胞IL-8分泌增加的潜在机制，丁酸盐上调IL-1 RI mRNA，但不上调IL-1 RII。丁酸盐预处理的IEC细胞系由IL-1 β刺激调节中性粒细胞迁移显着：减少向Caco-2和增强向HT-29/p细胞。蛋白酪氨酸磷酸酶的药理学抑制或用美沙拉嗪或柳氮磺胺吡啶治疗显著减少了丁酸盐暴露的HT-29细胞的IL-1 β刺激的IL-8分泌。丁酸盐对IEC的免疫调节作用与中性粒细胞迁移功能相关。药理学抑制IEC亚群中IL-1 β介导的IL-8分泌增强可能会改善丁酸盐的临床疗效。
Butyrate, a short-chain fatty acid released by colonic bacteria and administered therapeutically in inflammatory bowel diseases, exerts immunomodulatory properties. The aim of the study was to determine the functional consequences of butyrate exposure on the proinflammatory responsiveness of human intestinal epithelial cells (IEC). IL-8 promoter activity in IEC pretreated with butyrate then exposed to proinflammatory stimuli was assayed by transfection of luciferase constructs. IL-8 secretion was determined by ELISA and neutrophil migration by flow cytometry. Receptor mRNA was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR). Butyrate modulated proinflammatory IL-8 secretion differentially in Caco-2 and HT-29 cells on the transcriptional level. Pointing to the potentially underlying mechanism of increased IL-1beta-stimulated IL-8 secretion in HT-29 cells, butyrate up-regulated IL-1RI mRNA but not IL-1RII. Butyrate pretreatment of IEC lines stimulated by IL-1beta modulated neutrophil migration significantly: reduction towards Caco-2 and enhancement towards HT-29/p cells. Pharmacological inhibition of protein tyrosine phosphatases or treatment with mesalamine or sulphasalazine diminished IL-1beta-stimulated IL-8 secretion by butyrate-exposed HT-29 cells substantially. Immunomodulatory effects of butyrate on IEC are functionally relevant for neutrophil migration. Pharmacological inhibition of enhanced IL-1beta-mediated IL-8 secretion in a subpopulation of IEC may improve the clinical efficacy of butyrate.