Aryl Hydrocarbon Receptor Activation Down-Regulates IL-7 and Reduces Inflammation in a Mouse Model of DSS-Induced Colitis
Aryl Hydrocarbon Receptor Activation Down-Regulates IL-7 and Reduces Inflammation in a Mouse Model of DSS-Induced Colitis
复制标题
在 DSS 诱导的结肠炎小鼠模型中，芳基烃受体激活可下调 IL-7 并减少炎症
DOI：
10.1007/s10620-015-3632-x
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发表时间：
2015-07-01
影响因子：
3.1
通讯作者：
Yang, Hua
中科院分区：
文献类型：
--
作者：
Ji, Tao;Xu, Chao;Yang, Hua
背景与目的炎症性肠病（IBD）的发病机制与肠道免疫系统失调有关。芳烃受体（AHR）被认为控制肠道慢性炎症。此外，白细胞介素-7 （IL-7）被证明是IBD中激活粘膜炎症的重要细胞因子。此外，上皮内淋巴细胞（iel）是参与调节肠道炎症的关键免疫区室之一。在这项研究中，我们研究了AHR配体6-甲酰基林多洛（3,2-b）咔唑（Ficz）对IL-7、结肠炎和IEL表型的作用。方法采用右旋糖酐硫酸钠（DSS）诱导C57BL/6J野生型小鼠结肠炎7 d。称重小鼠，收集结肠组织并测量，进行组织学分析。从结肠中分离IELs，用流式细胞术检测IELs的表型和活化情况。采用免疫荧光、Western blot、RT-PCR检测AHR、IL-7的表达。结果ficz可下调dss诱导结肠炎小鼠上皮源性IL-7表达，改善dss诱导的结肠炎。Ficz还能降低CD8αβ+和CD8+IEL亚群，提高TCRγδ+IEL亚群，降低CD4+和CD8+亚群的活化率。结论ficz可下调dss诱导结肠炎小鼠上皮源性IL-7表达，抑制小鼠胃肠道炎症反应。ahr相关化合物可能是治疗IBD患者的新的和有前途的治疗药物。
Background and AimsThe pathogenesis of inflammatory bowel disease (IBD) is associated with dysregulation of intestinal immune system. Aryl hydrocarbon receptor (AHR) is believed to control the chronic inflammation in the gut. Besides, interleukin-7 (IL-7) is proved to be an important cytokine that activates mucosal inflammation in IBD. Moreover, intraepithelial lymphocytes (IELs) are one of the key immunological compartments involved in regulating intestinal inflammation. In this study, we investigated the function of 6-formylindolo (3,2-b) carbazole (Ficz), a ligand of AHR, on IL-7, colitis, and IEL phenotypes.MethodsColitis was induced by administration of dextran sulfate sodium (DSS) to wild-type C57BL/6J mice for 7 days. Mice were weighted, colon tissues were collected and measured, and histology analyses were performed. IELs were isolated from colon, and the phenotype and activation of IELs were examined using flow cytometry detection. The expression of AHR and IL-7 was measured by immunofluorescence, Western blot, and RT-PCR.ResultsFicz down-regulated epithelial-derived IL-7 expression in mice with DSS-induced colitis and ameliorated DSS-induced colitis. Ficz also decreased CD8αβ+and CD8+IEL subpopulations, enhanced TCRγδ+IEL subpopulation, and reduced the percentage of activated CD4+and CD8+subpopulations.ConclusionsFicz could down-regulate epithelial-derived IL-7 expression in mice with DSS-induced colitis and inhibit inflammation in the gastrointestinal tract of mice. AHR-related compounds might be the new and promising therapeutic medicaments for the treatment of patients with IBD.