微生物代谢物对体外人肠上皮细胞和巨噬细胞的影响

Marleen H.M.C. van Nuenen , Rianne A.F. de Ligt , Robert P. Doornbos , Janneke C.J. van der Woude , Ernst J. Kuipers , Koen Venema
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引用次数: 43

摘要

微生物代谢物可能影响肠上皮细胞的代谢完整性并诱导粘膜免疫反应。因此,我们研究了微生物代谢物丁酸盐、异戊酸盐和铵对Caco-2细胞和巨噬细胞的影响。屏障功能是通过测量经上皮电阻和代谢物的基底侧回收率来确定的。暴露后Caco-2细胞的屏障功能保持完整。底外侧加样回收率为6.2% ~ 15.2%。检测肿瘤坏死因子-α和白细胞介素-10的免疫反应。Caco-2细胞不分泌这两种细胞因子。生理浓度的丁酸盐和异戊酸盐刺激肿瘤坏死因子-α的分泌,抑制不受上皮屏障保护的巨噬细胞分泌白细胞介素-10。相反,当屏障功能受损时,IBD患者体内微生物群产生的高铵浓度会抑制这两种细胞因子的释放。
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The influence of microbial metabolites on human intestinal epithelial cells and macrophages in vitro

Microbial metabolites may influence the metabolic integrity of intestinal epithelial cells and induce mucosal immune responses. Therefore, we investigated the effects of the microbial metabolites butyrate, iso-valerate, and ammonium on Caco-2 cells and macrophages. Barrier functioning was determined by measuring transepithelial electrical resistance and basolateral recoveries of metabolites. The barrier function of Caco-2 cells remained intact after exposures. Basolateral recoveries ranged from 6.2% to 15.2%. Tumour necrosis factor-α and interleukin-10 were measured to determine immune reactions. The Caco-2 cells did not secrete both cytokines. Physiological concentrations of butyrate and iso-valerate stimulated the secretion of tumour necrosis factor-α and suppressed the secretion of interleukin-10 by macrophages that are not protected by an epithelial barrier. In contrast, ammonium concentrations as high as those produced by microbiotas of IBD patients suppressed the release of both cytokines when the barrier function is impaired.

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