Zheng Bin, Morgan Mary E, van de Kant Hendrik J G, Garssen Johan, Folkerts Gert, Kraneveld Aletta D
Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht 3586 CG, The Netherlands.
Nutricia Research, Utrecht 3508 TB, The Netherlands.
Biochem Biophys Rep. 2017 Aug 22;12:29-39. doi: 10.1016/j.bbrep.2017.08.009. eCollection 2017 Dec.
Pattern recognition receptors (PRRs) may contribute to inflammatory bowel diseases (IBD) development due to their microbial-sensing ability and the unique microenvironment in the inflamed gut. In this study, the PRR mRNA expression profile together with T cell-associated factors in the colon was examined using a chronic colitis mice model. 8-12 week old C57BL/6 mice were exposed to multiple dextran sodium sulfate (DSS) treatments interspersed with a rest period to mimic the course of chronic colitis. The clinical features and histological data were collected. The mRNA expressions of colonic PRRs, T cell-associated components were measured. Finally, the colons were scored for Foxp3+ cells. During chronic colitis, the histological data, but not the clinical manifestations demonstrated characteristic inflammatory symptoms in the distal colon. In contrast to acute colitis, the expression of all , except and , was unaffected after repeated DSS treatments. The expression of was decreased, while increased. After third DSS treatment, only the expressions of and were significantly enhanced. Unlike other PRRs, decreased and increased mRNA expression persisted during the chronic colitis period. As the colitis progress, only the mRNA expression of and staid increased during chronic colitis, while the acute colitis-associated increase of and and was abolished. Finally, increased histological score of Foxp3+ cell in colon was found during the chronic colitis period. This study provides an expression pattern of PRRs during chronic colitis that is accompanied by a Th1- and Th17 cell-mediated immune response.
模式识别受体(PRRs)因其微生物感知能力以及炎症肠道中独特的微环境,可能在炎症性肠病(IBD)的发展中发挥作用。在本研究中,使用慢性结肠炎小鼠模型检测了结肠中PRR mRNA表达谱以及T细胞相关因子。将8至12周龄的C57BL/6小鼠多次暴露于葡聚糖硫酸钠(DSS),期间穿插休息期,以模拟慢性结肠炎的病程。收集临床特征和组织学数据。测量结肠PRRs、T细胞相关成分的mRNA表达。最后,对结肠中的Foxp3 +细胞进行评分。在慢性结肠炎期间,组织学数据而非临床表现显示远端结肠出现特征性炎症症状。与急性结肠炎不同,除了 和 外,所有其他的 在反复DSS处理后表达未受影响。 的表达降低,而 升高。在第三次DSS处理后,只有 和 的表达显著增强。与其他PRRs不同,在慢性结肠炎期间, 和 的mRNA表达持续降低和升高。随着结肠炎进展,在慢性结肠炎期间只有 和 的mRNA表达持续升高,而急性结肠炎相关的 、 和 的升高消失。最后,在慢性结肠炎期间发现结肠中Foxp3 +细胞的组织学评分增加。本研究提供了慢性结肠炎期间PRRs的表达模式,其伴随着Th1和Th17细胞介导的免疫反应。