Effect of adiponectin on murine colitis induced by dextran sulfate sodium
Effect of adiponectin on murine colitis induced by dextran sulfate sodium
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DOI：
10.1053/j.gastro.2006.06.015
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发表时间：
2006-09-01
期刊：
影响因子：
29.4
通讯作者：
Shimomura, Iichiro
中科院分区：
文献类型：
--
作者：
Nishihara, Tamao;Matsuda, Morihiro;Shimomura, Iichiro
背景和目标：脂联素是一种脂肪组织来源的激素，具有抗炎作用，并具有多种生物学功能，如增加胰岛素敏感性，降低高血压，抑制动脉粥样硬化，肝纤维化和肿瘤生长。本研究的目的是确定脂联素对肠道炎症的影响。研究方法：我们通过脂联素基因敲除（APN-KO）小鼠和腺病毒介导的脂联素表达系统研究了脂联素对葡聚糖硫酸钠（DSS）诱导的结肠炎的影响。我们还研究了脂联素缺乏对三硝基苯磺酸（TNBS）诱导的结肠炎的作用。在体外，我们研究了脂联素对肠上皮细胞的影响。结果：给予0.5%DSS 15天后，与野生型小鼠相比，APN-KO小鼠发生了更严重的结肠炎。与野生型小鼠相比，DSS处理的APN-KO小鼠的结肠组织中趋化因子的信使RNA表达水平显著更高，伴有细胞浸润增加，包括巨噬细胞。腺病毒介导的脂联素补充显著减轻了结肠炎的严重程度，但两组之间TNBS诱导的结肠炎的严重程度没有差异。肠上皮细胞表达脂联素受体，脂联素抑制脂多糖诱导的肠上皮细胞产生白细胞介素8。结论：脂联素对DSS诱导的小鼠结肠炎具有保护作用，这可能是由于抑制肠上皮细胞中趋化因子的产生和随后的炎症反应，包括巨噬细胞的浸润和促炎细胞因子的释放。
Background & Aims: Adiponectin, an adipose tissue-derived hormone, exhibits anti-inflammatory properties and has various biological functions, such as increasing insulin sensitivity, reducing hypertension, and suppressing atherosclerosis, liver fibrosis, and tumor growth. The aim of the present study was to determine the effect of adiponectin on intestinal inflammation. Methods: We investigated the effect of adiponectin on dextran sulfate sodium (DSS)-induced colitis by using adiponectin-knockout (APN-KO) mice and an adenovirus-mediated adiponectin expression system. We also examined the contribution of adiponectin deficiency to trinitrobenzene sulfonic acid (TNBS)-induced colitis. In vitro, we examined the effect of adiponectin on intestinal epithelial cells. Results: After administration of 0.5% DSS for 15 days, APN-KO mice developed much more severe colitis compared with wild-type mice. The messenger RNA expression levels of chemokines were significantly higher in the colonic tissues of DSS-treated APN-KO mice compared with wild-type mice, accompanied by increased cellular infiltration, including macrophages. Adenovirus-mediated supplementation of adiponectin significantly attenuated the severity of colitis, but there were no differences in the severity of TNBS-induced colitis between the 2 groups. Adiponectin receptors were expressed in intestinal epithelial cells, and adiponectin inhibited lipopolysaccharide-induced interleukin-8 production in intestinal epithelial cells. Conclusions: Adiponectin is protective against DSS-induced murine colitis, probably due to the inhibition of chemokine production in intestinal epithelial cells and the following inflammatory responses, including infiltration of macrophages and release of proinflammatory cytokines.