Mucosal immunosuppression and epithelial barrier defects are key events in murine psychosocial stress-induced colitis
Mucosal immunosuppression and epithelial barrier defects are key events in murine psychosocial stress-induced colitis
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DOI：
10.1016/j.bbi.2011.03.004
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发表时间：
2011-08-01
影响因子：
15.1
通讯作者：
Obermeier, Florian
中科院分区：
文献类型：
--
作者：
Reber, Stefan O.;Peters, Sebastian;Obermeier, Florian
慢性心理社会压力是许多情感和躯体疾病的危险因素，包括炎症性肠病。在支持慢性从属群体住房(CSC，19天)中，建立了慢性心理社会应激的小鼠模型，导致自发性结肠炎的发展。然而，这种应激诱导结肠炎的发病机制尚不清楚。在最初的应激阶段评估结肠的几个功能水平，我们发现明显的肾上腺激素介导的局部免疫抑制，同时伴随着肠道屏障功能的受损，导致粪便和结肠组织中细菌负荷的增加。此外，广谱抗生素的长期治疗揭示了这些早期适应不良在应激诱导结肠炎发展中的原因作用。同时，我们证明共生细菌的易位在应激诱导结肠炎的启动中至关重要。然而，肾上腺激素水平波动的免疫调节作用需要加重，才能将其发展成全面的结肠炎。(C)2011 Elsevier Inc.保留所有权利。
Chronic psychosocial stress is a risk factor for many affective and somatic disorders, including inflammatory bowel diseases. In support chronic subordinate colony housing (CSC, 19 days), an established mouse model of chronic psychosocial stress, causes the development of spontaneous colitis. However, the mechanisms underlying the development of such stress-induced colitis are poorly understood. Assessing several functional levels of the colon during the initial stress phase, we show a pronounced adrenal hormone-mediated local immune suppression, paralleled by impaired intestinal barrier functions, resulting in enhanced bacterial load in stool and colonic tissue. Moreover, prolonged treatment with broad-spectrum antibiotics revealed the causal role of these early maladaptations in the development of stress-induced colitis.Together, we demonstrate that translocation of commensal bacteria is crucial in the initiation of stress-induced colonic inflammation. However, aggravation by the immune-modulatory effects of fluctuating levels of adrenal hormones is required to develop this into a full-blown colitis. (C) 2011 Elsevier Inc. All rights reserved.