CXC趋化因子受体2和白细胞介素-8在炎症性肠病患者中的表达及其意义

Expressions and Significance of CXC Chemokine Receptor Type 2 and Interleukin-8 in Patients with Inflammatory Bowel Disease

背景:CXC趋化因子受体2(CXCR2)为G蛋白耦联受体超家族成员,主要参与肿瘤生长、血管形成以及炎症性疾病的发病,有研究显示其参与炎症性肠病(IBD)发病,但相关作用仍未明确。研究表明白细胞介素-8(IL-8)与CXCR1和CXCR2的相互作用在IBD发病中发挥重要作用。目的:探讨CXCR2和IL-8在IBD患者中的表达及其意义。方法:纳入武汉大学中南医院2013年10月—2014年12月收治的活动期IBD患者121例,分为克罗恩病(CD)组和溃疡性结肠炎(UC)组,选取70例同期健康体检者作为正常对照(HC)组。采用real-time PCR检测外周血和肠黏膜组织IL-8和CXCR2 mRNA表达;采用蛋白质印迹法检测肠黏膜组织CXCR2蛋白表达。结果:UC组外周血IL-8 mRNA表达水平显著高于HC组(P=0.017);CD组、UC组和HC组外周血CXCR2 mRNA表达水平无明显差异(P=0.285)。CD组、UC组和HC组肠黏膜组织IL-8 mRNA表达水平无明显差异(P=0.206);CD组和UC组肠黏膜组织CXCR2 mRNA表达水平显著高于HC组(P=0.002;P<0.001),且UC组显著高于CD组(P=0.005)。UC组和CD组肠黏膜组织CXCR2蛋白表达水平高于HC组(P=0.049;P=0.080)。结论:IBD患者肠黏膜组织CXCR2 mRNA和蛋白表达均显著上调,且以UC患者为著,下调肠黏膜CXCR2表达可为治疗UC提供新靶点。IL-8主要在UC患者外周血中高表达,提示IL-8主要与UC发病相关。

Background： CXC chemokine receptor type 2 （CXCR2） is a member of G protein coupled receptor superfamily, and is mainly involved in the growth of tumor, angiogenesis and the pathogenesis of inflammatory diseases. Studies showed that CXCR2 was associated with the pathogenesis of inflammatory bowel disease （IBD）, but the exact role has not yet been clarified. It was found that the interaction of interleukin-8 （IL-8） with CXCR1 and CXCR2 played an important role in the pathogenesis of IBD. Aims： To investigate the expressions and significance of CXCR2 and IL-8 in patients with IBD. Methods： A total of 121 IBD patients in active stage from October 2013 to December 2014 at Zhongnan Hospital of Wuhan University were enrolled and assigned into Crohn＇ s disease （CD） group and ulcerative colitis （UC） group. Seventy healthy subjects were served as controls （HC）. Expressions of IL-8 mRNA and CXCR2 mRNA in peripheral blood and intestinal mucosal tissue were determined by real-time PCR; expression of CXCR2 protein in intestinal mucosal tissue was determined by Western blotting. Results： In peripheral blood, expression of IL-8 mRNA in UC group was significantly higher than that in HC group （P = 0.017）, while expressions of CXCR2 mRNA in CD, UC and HC groups were not significantly different （P = 0. 285）. In intestinal mucosal tissue, expressions of IL-8 mRNA in CD, UC and HC groups showed no significant difference （P = 0.206）, while expressions of CXCR2 mRNA in CD and UC groups were significantly higher than that in HC group （ P = 0. 002 ; P 〈 0.001 ）, and expression of CXCR2 mRNA in UC group was significantly higher than that in CD group （P = 0. 005 ） ; expressions of CXCR2 protein in UC and CD groups were higher than that in HC group （P = 0. 049 ;P = 0. 080）. Conclusions ： Expressions of CXCR2 mRNA and protein in intestinal mucosal tissue of patients with IBD, especially UC are significantly increased. Down regulation of CXCR2 expression in intestinal mucosa may provide a new target for treatment of UC. IL-8 is significantly highly expressed in peripheral blood of patients with UC, which suggests that IL-8 might be related mainly with UC.