Sodium Butyrate Inhibits Inflammation and Maintains Epithelium Barrier Integrity in a TNBS-induced Inflammatory Bowel Disease Mice Model

作者：Guangxin Chen, Xin Ran, Bai Li, Yuhang Li, Dewei He, Bingxu Huang, Shoupeng Fu, Juxiong Liu, Wei Wang · 发表于：EBioMedicine · 年份：2018 · DOI：10.1016/j.ebiom.2018.03.030 · 被引用次数：589 · 研究领域：Inflammatory Bowel Disease、Immune Cell Function and Interaction、Eosinophilic Esophagitis

G Protein Coupled Receptor 109A (GPR109A), which belongs to the G protein coupled receptor family, can be activated by niacin, butyrate, and β-hydroxybutyric acid. Here, we assessed the anti-inflammatory activity of sodium butyrate (SB) on 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis mice, an experimental model that resembles Crohn's disease, and explored the potential mechanism of SB in inflammatory bowel disease (IBD). In vivo , experimental GPR109a −/− and wild-type ( WT ) mice were administered SB (5g/L) in their drinking water for 6weeks. The mice were then administered TNBS via rectal perfusion to imitate colitis. In vitro , RAW246.7 macrophages, Caco-2 cells, and primary peritoneal macrophages were used to investigate the protective roles of SB on lipopolysaccharide (LPS)-induced inflammatory response and epithelium barrier dysfunction. In vivo , SB significantly ameliorated the inflammatory response and intestinal epithelium barrier dysfunction in TNBS-induced WT mice, but failed to provide a protective effect in TNBS-induced GPR109a −/− mice. In vitro , pre-treatment with SB dramatically inhibited the expression of TNF-α and IL-6 in LPS-induced RAW246.7 macrophages. SB inhibited the LPS-induced phosphorylation of the NF-κB p65 and AKT signaling pathways, but failed to inhibit the phosphorylation of the MAPK signaling pathway. Our data indicated that SB ameliorated the TNBS-induced inflammatory response and intestinal epithelium barrier dysfunction throu...