Piroxicam treatment of IL-10-deficient mice enhances colonic epithelial apoptosis and mucosal exposure to intestinal bacteria
Piroxicam treatment of IL-10-deficient mice enhances colonic epithelial apoptosis and mucosal exposure to intestinal bacteria
复制标题
DOI：
10.1097/01.mib.0000187582.90423.bc
复制
发表时间：
2005-12-01
影响因子：
4.9
通讯作者：
Swidinski, A
中科院分区：
文献类型：
--
作者：
Hale, LP;Gottfried, MR;Swidinski, A
最近显示，使用非甾体抗炎药吡罗昔康或舒林酸治疗可加速白细胞介素 (IL)-10 缺陷 (IL-10(-/-)) 小鼠结肠炎的发展。尽管 NSAID 被假设会降低肠上皮的屏障功能，但其加速 IL-10(-/-) 小鼠结肠炎的机制尚不清楚。在这项研究中，从组织学角度评估了吡罗昔康油对IL-10(-/-) C57BL/6小鼠结肠粘膜的影响。使用比色法和荧光测定法评估吡罗昔康油对肠上皮细胞的体外作用，以评估细胞活力和细胞凋亡。通过 rRNA 引导的荧光原位杂交评估肠道细菌与结肠粘膜的相互作用。口服吡罗昔康对C57BL/6 IL-10-/-小鼠体内治疗显着增强结肠上皮细胞凋亡，导致粘膜表面局灶性糜烂，增强细菌粘附和侵袭，加速结肠炎的发展。在体外，吡罗昔康以剂量依赖性方式诱导 CT26 小鼠肠上皮细胞凋亡。吡罗昔康诱导的CT26细胞凋亡不能通过添加外源IL-10来阻止；然而，IL-10 确实显着提高了它们的增殖速度。因此，暴露于吡罗昔康在体外和体内均增强肠上皮细胞凋亡，并促进肠道细菌在体内粘附和侵入粘膜组织。 IL-I 0在此过程中的作用需要进一步研究。这些研究支持文件假设，即粘膜细胞与肠道细菌的接触增加可能导致 IL-10(-/-) 或其他遗传易感个体发生肠道炎症。
Treatment with the nonsteroidal anti-inflammatory drugs piroxicam or sulindac was recently shown to accelerate the development of colitis in interleukin (IL)-10-deficient (IL-10(-/-)) mice. Although NSAIDs have been hypothesized to decrease the barrier function of the intestinal epithelium, the mechanism by which this accelerates colitis in IL-10(-/-) mice is not Well understood. In this study, the effects of piroxicam oil the colonic mucosa of IL-10(-/-) C57BL/6 mice were evaluated histologically. The effect of piroxicam oil intestinal epithelial cells in vitro was assessed using colorimetric and fluorescent assays for cell viability and apoptotic cell death. Interactions of intestinal bacteria with the colonic mucosa were evaluated by rRNA-directed fluorescence in situ hybridization. In vivo treatment of C57BL/6 IL-10-/- mice with oral piroxicam markedly enhanced apoptosis of colonic epithelium and resulted in focal erosion Of the mucosal surface, enhanced bacterial adhesion and invasion, and accelerated the development of colitis. In vitro, piroxicam induced apoptosis of CT26 murine intestinal epithelial cells in a dose-dependent fashion. Piroxicam-induced apoptosis of CT26 cells Could not be prevented by addition of exogenous IL-10; however, IL-10 did significantly enhance their rate of proliferation. Thus, exposure to piroxicam enhances intestinal epithelial apoptosis both in vitro and in vivo and facilitates adhesion and invasion of intestinal bacteria into mucosal tissues in vivo. The role of IL-I 0 in this process requires further study. These studies Support file hypothesis that increased exposure of mucosal cells to intestinal bacteria may lead to development of intestinal inflammation in IL-10(-/-) or other genetically susceptible individuals.