CRH, the hypothalamic component of the hypothalamic-pituitary adrenal axis, attenuates inflammation through stimulation of glucocorticoid release, whereas peripherally expressed CRH acts as a proinflammatory mediator. CRH is expressed in the intestine and up-regulated in patients with ulcerative colitis. However, its pathophysiological significance in intestinal inflammatory diseases has just started to emerge. In a mouse model of acute, trinitrobenzene sulfonic acid-induced experimental colitis, we demonstrate that, despite low glucocorticoid levels, CRH-deficient mice develop substantially reduced local inflammatory responses. These effects were shown by histological scoring of tissue damage and neutrophil infiltration. At the same time, CRH deficiency was found to be associated with higher serum leptin and IL-6 levels along with sustained anorexia and weight loss, although central CRH has been reported to be a strong appetite suppressor. Taken together, our results support an important proinflammatory role for CRH during mouse experimental colitis and possibly in inflammatory bowel disease in humans. Moreover, the results suggest that CRH is involved in homeostatic pathways that link inflammation and metabolism.

译文

:CRH,下丘脑-垂体肾上腺轴的下丘脑成分,通过刺激糖皮质激素释放来减轻炎症,而外周表达的CRH则充当促炎介质。 CRH在溃疡性结肠炎患者的肠中表达并上调。然而,其在肠道炎性疾病中的病理生理意义才刚刚开始显现。在急性三硝基苯磺酸诱导的实验性结肠炎的小鼠模型中,我们证明,尽管糖皮质激素水平较低,但CRH缺陷型小鼠的局部炎症反应却大大降低。组织损伤和中性粒细胞浸润的组织学评分显示了这些作用。同时,CRH缺乏症与血清瘦素和IL-6水平升高以及持续的厌食和体重减轻有关,尽管据报道中枢性CRH是强烈的食欲抑制剂。两者合计,我们的结果支持在小鼠实验性结肠炎期间CRH的重要促炎作用,并可能在人类的炎症性肠病中。此外,结果表明CRH参与了连接炎症和新陈代谢的体内平衡途径。

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