Corticotropin releasing hormone promotes inflammatory bowel disease via inducing intestinal macrophage autophagy.
Corticotropin releasing hormone promotes inflammatory bowel disease via inducing intestinal macrophage autophagy.
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促肾上腺皮质激素释放激素通过诱导肠道巨噬细胞自噬促进炎症性肠病。
DOI：
10.1038/s41420-021-00767-8
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发表时间：
2021-12-07
影响因子：
7
通讯作者：
Bai Y
中科院分区：
文献类型：
--
作者：
Zhao SB;Wu JY;He ZX;Song YH;Chang X;Xia T;Fang X;Li ZS;Xu C;Wang SL;Bai Y
心理社会应激是炎症性肠病（IBD）发病和进展的重要因素。肠巨噬细胞自噬在IBD发病和发展中的作用已被广泛研究。在此，我们研究了IBD小鼠模型中与巨噬细胞自噬有关的心理社会应激的潜在机制。促肾上腺皮质激素释放激素（CRH）外周给药，以诱导心理社会应激。对于体内研究，葡聚糖硫酸钠（DSS）用于创建我们的IBD小鼠模型。对于体外研究，将脂多糖（LPS）应用于小鼠骨髓源性巨噬细胞（BMDM）作为IBD相关的细胞激发。应用氯喹抑制自噬。我们发现CRH加重DSS诱导的IBD的严重程度，增加整体和局部炎症反应和浸润。肠巨噬细胞和小鼠BMDM中的自噬水平在这些IBD相关的炎症挑战下增加，CRH进一步增强了这些作用。随后给予氯喹通过抑制自噬显著减弱CRH对IBD严重程度和炎症反应的不利影响。这些发现说明CRH外周给药通过增强肠道巨噬细胞自噬对DSS诱导的IBD的影响，从而为IBD的治疗提供了新的认识和治疗靶点。
Psychosocial stress is a vital factor contributing to the pathogenesis and progression of inflammatory bowel disease (IBD). The contribution of intestinal macrophage autophagy to the onset and development of IBD has been widely studied. Herein, we investigated the underlying mechanism of psychosocial stress in an IBD mouse model pertaining to macrophage autophagy. Corticotropin releasing hormone (CRH) was peripherally administrated to induce psychosocial stress. For in vivo studies, dextran sulfate sodium (DSS) was used for the creation of our IBD mouse model. For in vitro studies, lipopolysaccharide (LPS) was applied on murine bone marrow-derived macrophages (BMDMs) as a cellular IBD-related challenge. Chloroquine was applied to inhibit autophagy. We found that CRH aggravated the severity of DSS-induced IBD, increasing overall and local inflammatory reactions and infiltration. The levels of autophagy in intestinal macrophages and murine BMDMs were increased under these IBD-related inflammatory challenges and CRH further enhanced these effects. Subsequent administration of chloroquine markedly attenuated the detrimental effects of CRH on IBD severity and inflammatory reactions via inhibition of autophagy. These findings illustrate the effects of peripheral administration of CRH on DSS-induced IBD via the enhancement of intestinal macrophage autophagy, thus providing a novel understanding as well as therapeutic target for the treatment of IBD.
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影响因子：
24.5
作者：
Palmela, Carolina;Chevarin, Caroline;Colombel, Jean-Frederic
通讯作者：
Colombel, Jean-Frederic
DOI：
10.1152/ajpendo.00221.2017
发表时间：
2018-08-01
影响因子：
5.1
作者：
Gavin, Kathleen M.;Shea, Karen L.;Kohrt, Wendy M.
通讯作者：
Kohrt, Wendy M.
DOI：
10.1126/science.aad9948
发表时间：
2016-05-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Chu H;Khosravi A;Kusumawardhani IP;Kwon AH;Vasconcelos AC;Cunha LD;Mayer AE;Shen Y;Wu WL;Kambal A;Targan SR;Xavier RJ;Ernst PB;Green DR;McGovern DP;Virgin HW;Mazmanian SK
通讯作者：
Mazmanian SK
影响因子：
20.1
作者：
Gatica D;Chiong M;Lavandero S;Klionsky DJ
通讯作者：
Klionsky DJ
多巴胺系统参与慢性内脏痛大鼠模型室旁核脑促肾上腺皮质激素释放激素的调节
影响因子：
1.9
作者：
Ji, Ning-Ning;Kang, Jie;Zhang, Yong-Mei
通讯作者：
Zhang, Yong-Mei