Resveratrol Ameliorates Intestinal Barrier Defects and Inflammation in Colitic Mice and Intestinal Cells
Resveratrol Ameliorates Intestinal Barrier Defects and Inflammation in Colitic Mice and Intestinal Cells
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DOI：
10.1021/acs.jafc.8b04138
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发表时间：
2018-12-05
影响因子：
6.1
通讯作者：
Suzuki, Takuya
中科院分区：
文献类型：
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作者：
Mayangsari, Yunika;Suzuki, Takuya
本研究旨在探讨白藜芦醇对右旋糖酐硫酸钠（DSS）诱导的结肠炎小鼠模型和肠道Caco-2细胞的改善作用，重点关注中性粒细胞浸润和紧密连接（TJ）屏障。DSS政府造成身体减肥(day8、控制104 + / - 1、DSS 72 + / - 2%, p < 0.05),结肠长度的缩短(控制5.1 + / - 0.1,DSS 3.8 + / - 0.1厘米,p < 0.05),促炎细胞因子increase-including白介素(IL) 1β(控制1.0 + / - 0.2,DSS任意单元(AU) 58.5 + / - 29.6, p < 0.05), IL - 6(控制1.0 + / - 0.3,DSS 312 + / - 82 AU, p < 0.05),和趋化因子配体2主题(小鼠引发同系物CXCL-2,控制1.0 + / - 0.4,DSS 696 + / - 262 AU, p < 0.05),TJ蛋白（如occludin，对照组1.0 +/- 0.05,DSS 0.11 +/- 0.03 AU, p < 0.05）和中性粒细胞浸润（对照组1.2 +/- 0.2,DSS 25.9 +/- 1.1细胞，p < 0.05）降低。添加白藜芦醇（日粮中0.1% (w/w)）部分或完全逆转了这些症状（体重变化100 +/- 1，结肠长度4.6 +/- 0.1,IL-1 β 5.9 +/- 1.8, IL-6 10 +/- 3, CXCL-2 14 +/- 7, occludin 0.76 +/- 0.06，中性粒细胞浸润9.3 +/- 0.7,p < 0.05）。白藜芦醇预处理肠道Caco-2细胞可抑制TNF- α诱导的IL-8生成（对照1.00 +/- 0.04,TNF- α 3.40 +/- 0.16, TNF- α +Res 1.81 +/- 0.28 AU, p < 0.05）和炎症信号分子NF-kappa B、细胞外信号调节激酶和应激c-Jun n端蛋白激酶磷酸化。总的来说，肠道细胞中TJ屏障缺陷和IL-8的减少，导致中性粒细胞向结肠组织的浸润减少，似乎是白藜芦醇介导作用的主要机制之一。
This study is aimed to investigate the ameliorative effect of resveratrol in a dextran sodium sulfate (DSS)-induced colitis mouse model and intestinal Caco-2 cells, focusing on neutrophil infiltration and tight junction (TJ) barriers. DSS administration caused body weight loss (day8, control 104 +/- 1, DSS 72 +/- 2%, p < 0.05), shortening of colon length (control 5.1 +/- 0.1, DSS 3.8 +/- 0.1 cm, p < 0.05), pro-inflammatory cytokines increase-including interleukin (IL)-1 beta (control 1.0 +/- 0.2, DSS 58.5 +/- 29.6 arbitrary unit (AU), p < 0.05), IL-6 (control 1.0 +/- 0.3, DSS 312 +/- 82 AU, p < 0.05), and chemokine motif ligand 2 (CXCL-2, a murine IL-8 homologue, control 1.0 +/- 0.4, DSS 696 +/- 262 AU, p < 0.05), decreased TJ proteins (e.g., occludin, control 1.0 +/- 0.05, DSS 0.11 +/- 0.03 AU, p < 0.05), and neutrophil infiltration (control 1.2 +/- 0.2, DSS 25.9 +/- 1.1 cells, p < 0.05). Supplemental resveratrol (0.1% (w/w) in the diet) partially or totally reversed these symptoms (body weight change 100 +/- 1, colon length 4.6 +/- 0.1; IL-1 beta 5.9 +/- 1.8, IL-6 10 +/- 3, CXCL-2 14 +/- 7, occludin 0.76 +/- 0.06, neutrophil infiltration 9.3 +/- 0.7, p < 0.05). Pretreatment of intestinal Caco-2 cells with resveratrol suppressed the TNF-alpha-induced production of IL-8 (control 1.00 +/- 0.04, TNF alpha 3.40 +/- 0.16, TNF alpha+Res 1.81 +/- 0.28 AU, p < 0.05) and phosphorylation of the inflammatory signaling molecules including NF-kappa B, extracellular signal-regulated kinase and stress c-Jun N-terminal protein kinase. Collectively, the reduction of TJ barrier defect and IL-8 in intestinal cells, leading to reduced neutrophil infiltration into colonic tissues, appears to be one of the central mechanisms for the resveratrol-mediated effect.