Chen Weigang, Pu Aimin, Sheng Baifa, Zhang Zhicao, Li Liangzi, Liu Zhongze, Wang Qimeng, Li Xiang, Ma Yuanhang, Yu Min, Sun Lihua, Qiu Yuan, Yang Hua
Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Department of General Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Biomed Pharmacother. 2017 Mar;87:127-134. doi: 10.1016/j.biopha.2016.12.061. Epub 2016 Dec 31.
This research is dedicated to investigating the effects and potential mechanism of action of the aryl hydrocarbon receptor on the intestinal mucosal immune system in dextran sulfate sodium (DSS)-induced colitis.
Colitis was induced by the administration of 3% DSS to wild-type C57BL/6J mice for 7days. 6-formylindolo(3, 2-b)carbazole (FICZ), an endogenous agonist of the aryl hydrocarbon receptor (AhR), was given intraperitoneally on a daily basis beginning 2days after the start of DSS administration. The mice were weighed and assessed, and colon tissues were measured. Intraepithelial lymphocytes (IELs) were isolated from the colon and examined by flow cytometry and quantitative real-time PCR.
FICZ ameliorated DSS-induced colitis, resulting in a reduced disease activity index and improvement in the histology and length of the colon. Colitis reduced the percentage and number of CD8ααTCRαβ IELs. FICZ prevented the reduction in the numbers of CD8ααTCRαβ IELs by upregulating the expression of the IL-15 receptor and the aryl hydrocarbon receptor (AhR), and attenuating the apoptotic rate of CD8ααTCRαβ IELs. Finally, IL-10 was increased and IFN-γ was decreased in CD8ααTCRαβ IELs by FICZ administration in DSS-induced colitis.
The results suggest that AhR activation ameliorated DSS-induced acute colitis, in a manner that is associated with the local expansion and functions of CD8ααTCRαβ IELs in acute colitis. The findings indicate that AhR-related ligands might be targeted as novel drug targets for IBD.
本研究致力于探讨芳烃受体对葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠肠道黏膜免疫系统的作用及其潜在作用机制。
给野生型C57BL/6J小鼠灌胃3% DSS诱导结肠炎，持续7天。从DSS给药开始2天后，每天腹腔注射芳烃受体（AhR）的内源性激动剂6-甲酰基吲哚并[3,2-b]咔唑（FICZ）。对小鼠进行称重和评估，并测量结肠组织。从结肠分离上皮内淋巴细胞（IELs），通过流式细胞术和定量实时PCR进行检测。
FICZ改善了DSS诱导的结肠炎，导致疾病活动指数降低，结肠组织学和长度得到改善。结肠炎降低了CD8ααTCRαβ IELs的百分比和数量。FICZ通过上调IL-15受体和芳烃受体（AhR）的表达，减弱CD8ααTCRαβ IELs的凋亡率，从而防止CD8ααTCRαβ IELs数量的减少。最后，在DSS诱导的结肠炎中，FICZ给药使CD8ααTCRαβ IELs中的IL-10增加，IFN-γ减少。
结果表明，AhR激活改善了DSS诱导的急性结肠炎，其方式与急性结肠炎中CD8ααTCRαβ IELs的局部扩增和功能有关。研究结果表明，AhR相关配体可能成为治疗炎症性肠病的新型药物靶点。
