cxcr4 antagonist amd3100 modulates claudin expression and intestinal barrier function in experimental colitis趋化因子受体cxcr4拮抗剂amd3100调节claudin表达和肠道屏障功能实验结肠炎.pdfVIP

CXCR4 Antagonist AMD3100 Modulates Claudin Expression and Intestinal Barrier Function in Experimental Colitis 1 2 1 1 1 3 Xian-Ming Xia *, Fang-Yu Wang , Ju Zhou , Kai-Feng Hu , Su-Wen Li , Bing-Bing Zou 1 Department of Gastroenterology and Hepatology, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China, 2 Department of Gastroenterology and Hepatology, Jinling Hospital, Nanjing, Jiangsu Province, People’s Republic of China, 3 Department of General Surgery, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, People’s Republic of China Abstract Ulcerative colitis is a gastrointestinal disorder characterized by local inflammation and impaired epithelial barrier. Previous studies demonstrated that CXC chemokine receptor 4 (CXCR4) antagonists could reduce colonic inflammation and mucosal damage in dextran sulfate sodium (DSS)-induced colitis. Whether CXCR4 antagonist has action on intestinal barrier and the possible mechanism, is largely undefined. In the present study, the experimental colitis was induced by administration of 5% DSS for 7 days, and CXCR4 antagonist AMD3100 was administered intraperitoneally once daily during the study period. For in vitro study, HT-29/B6 colonic cells were treated with cytokines or AMD3100 for 24 h until assay. DSS-induced colitis was characterized by morphologic changes in mice. In AMD3100-treated mice, epithelial destruction, inflammatory infiltration, and submucosal edema were markedly reduced, and the disease activity index was also significantly decreased. Increased intestinal permeability in DSS-induced colitis was also significantly reduced by AMD3100. The expressions of