Butyrate inhibits inflammatory responses through NFκB inhibition:: implications for Crohn's disease
Butyrate inhibits inflammatory responses through NFκB inhibition:: implications for Crohn's disease
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DOI：
10.1136/gut.47.3.397
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发表时间：
2000-09-01
期刊：
影响因子：
24.5
通讯作者：
Galmiche, JP
中科院分区：
文献类型：
--
作者：
Segain, JP;de la Blétière, DR;Galmiche, JP
促炎细胞因子是克罗恩病（CD）发病机制中的关键因素。CD患者肠粘膜中参与其基因转录的核因子κ B（NF κ B B）的活化增加。作为丁酸盐灌肠剂可能是有益的，在治疗结肠炎症，我们调查，如果丁酸盐促进这种效果通过作用于促炎细胞因子expression. Methods肠活检标本，分离的固有层细胞（LPMC），和外周血单核细胞（PBMC）培养或不丁酸盐的分泌肿瘤坏死因子（TNF）和mRNA水平的评估。通过免疫荧光和基因报告实验测定NF κ B p65活化。通过蛋白质印迹法分析NF κ B抑制蛋白（I κ B α）的水平。丁酸盐的体内疗效进行了评估，在大鼠与三硝基苯磺酸（TNBS）诱导colis.Results-Butyrate降低TNF的产生和促炎细胞因子mRNA的表达，肠活检和LPMC CD患者。丁酸可阻断脂多糖（LPS）诱导的PBMC细胞因子表达和NF κ B B从细胞质向细胞核的迁移。丁酸盐降低了LPS诱导的NF κ B转录活性，而I κ B α水平稳定。丁酸盐治疗也改善TNBS诱导colis. Conclusions丁酸盐通过抑制NF κ B活化和I κ B α降解降低促炎细胞因子的表达。这些抗炎特性为评估丁酸盐治疗CD提供了依据。
Background/aim-Proinflammatory cytokines are key factors in the pathogenesis of Crohn's disease (CD). Activation of nuclear factor kappa B (NF kappa B), which is involved in their gene transcription, is increased in the intestinal mucosa of CD patients. As butyrate enemas may be beneficial in treating colonic inflammation, we investigated if butyrate promotes this effect by acting on proinflammatory cytokine expression.Methods-Intestinal biopsy specimens, isolated lamina propria cells (LPMC), and peripheral blood mononuclear cells (PBMC) were cultured with or without butyrate for assessment of secretion of tumour necrosis factor (TNF) and mRNA levels. NF kappa B p65 activation was determined by immunofluorescence and gene reporter experiments. Levels of NF kappa B inhibitory protein (I kappa B alpha) were analysed by western blotting. The in vivo efficacy of butyrate was assessed in rats with trinitrobenzene sulphonic acid (TNBS) induced colitis.Results-Butyrate decreased TNF production and proinflammatory cytokine mRNA expression by intestinal biopsies and LPMC from CD patients. Butyrate abolished lipopolysaccharide (LPS) induced expression of cytokines by PBMC and transmigration of NF kappa B from the cytoplasm to the nucleus. LPS induced NF kappa B transcriptional activity was decreased by butyrate while I kappa B alpha levels were stable. Butyrate treatment also improved TNBS induced colitis.Conclusions-Butyrate decreases proinflammatory cytokine expression via inhibition of NF kappa B activation and I kappa B alpha degradation. These anti-inflammatory properties provide a rationale for assessing butyrate in the treatment of CD.