Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function.
Interleukin-4 Receptor α Subunit Deficiency Alleviates Murine Intestinal Inflammation In Vivo Through the Enhancement of Intestinal Mucosal Barrier Function.
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白介素-4受体α亚基缺乏通过增强肠粘膜屏障功能来减轻体内鼠肠炎。
DOI：
10.3389/fphar.2020.573470
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发表时间：
2020
影响因子：
5.6
通讯作者：
Kadowaki M
中科院分区：
文献类型：
--
作者：
Hertati A;Hayashi S;Ogawa Y;Yamamoto T;Kadowaki M
上皮屏障功能障碍会导致慢性肠道炎症，例如炎症性肠道疾病。一些研究报道，Th 2细胞因子如白细胞介素（IL）-4和IL-13在肠屏障功能的调节中起重要作用。然而，IL-4受体α亚基（IL-4 R α）在肠道炎症中的确切作用仍不清楚。因此，我们使用实验性结肠炎模型来研究IL-4 R α在肠道炎症中的作用。使用IL-4 R α缺陷（IL-4 R α-/-）小鼠及其同窝野生型（WT）小鼠。通过在饮用水中给予3%葡聚糖硫酸钠（DSS）连续7天诱导实验性结肠炎。DSS给药导致WT结肠炎小鼠体重减轻、疾病活动指数增加和组织学异常，所有这些在IL-4 R α-/-结肠炎小鼠中均显著减弱。与WT结肠炎小鼠相比，IL-4 R α-/-结肠炎小鼠结肠粘膜中的神经元浸润减少。IL-4 R α-/-小鼠结肠中NADPH氧化酶1表达和活性氧产生增加。此外，在IL-4 R α-/-结肠炎小鼠中，DSS处理诱导的肠通透性升高受到抑制。这些结果表明，IL-4 R α-/-小鼠对DSS诱导的结肠炎的易感性降低。我们目前的研究结果表明，IL-4 R α缺乏通过上调NADPH氧化酶1依赖性活性氧的产生来增强肠粘膜屏障功能，从而抑制肠道炎症的发展。
Disturbance of epithelial barrier function causes chronic intestinal inflammation such as inflammatory bowel disease. Several studies have reported that Th2 cytokines such as interleukin (IL)-4 and IL-13 play an important role in the regulation of intestinal barrier function. However, the precise role of the IL-4 receptor α subunit (IL-4Rα) in intestinal inflammation remains unclear. Thus, we used an experimental colitis model to investigate the role of IL-4Rα in intestinal inflammation. IL-4Rα-deficient (IL-4Rα-/-) mice and their littermate wild-type (WT) mice were used. Experimental colitis was induced by administration of 3% dextran sulfate sodium (DSS) in the drinking water for seven days. Treatment with DSS caused body weight loss, an increase in the disease activity index and histological abnormalities in WT colitis mice, all of which were significantly attenuated in IL-4Rα-/- colitis mice. Neutrophil infiltration in the colonic mucosa was reduced in IL-4Rα-/- colitis mice compared with WT colitis mice. NADPH oxidase 1 expression and reactive oxygen species production were increased in the colons of IL-4Rα-/- mice. Furthermore, elevated intestinal permeability induced by DSS treatment was suppressed in IL-4Rα-/- colitis mice. These results demonstrate that IL-4Rα-/- mice exhibit reduced susceptibility to DSS-induced colitis. Our present findings suggest that IL-4Rα deficiency enhances intestinal mucosal barrier function through the upregulation of NADPH oxidase 1-dependent reactive oxygen species production, thereby suppressing the development of intestinal inflammation.
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影响因子：
14.2
作者：
Groschwitz, Katherine R.;Hogan, Simon P.
通讯作者：
Hogan, Simon P.
影响因子：
5.3
作者：
Coant, Nicolas;Ben Mkaddem, Sanae;Ogier-Denis, Eric
通讯作者：
Ogier-Denis, Eric
DOI：
10.1124/jpet.108.145862
发表时间：
2009-04-01
影响因子：
3.5
作者：
Farooq, Shukkur Muhammed;Stillie, RoseMarie;Stadnyk, Andrew W.
通讯作者：
Stadnyk, Andrew W.
影响因子：
29.7
作者：
Kaser A;Zeissig S;Blumberg RS
通讯作者：
Blumberg RS
影响因子：
4.4
作者：
Madden, KB;Whitman, L;Shea-Donohue, T
通讯作者：
Shea-Donohue, T