Role of inducible cyclooxygenase and prostaglandins in Clostridium difficile toxin A-induced secretion and inflammation in an animal model

被引:40
作者
Alcantara, C
Stenson, WF
Steiner, TS
Guerrant, RL
机构
[1] Univ Virginia, Dept Med, Div Geog Med, Charlottesville, VA 22908 USA
[2] Washington Univ, Dept Internal Med, Div Gastroenterol, St Louis, MO USA
关键词
D O I
10.1086/322799
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Cyclooxygenase (Cox)-2 expression and inhibition were investigated in a rabbit ileal loop model of Clostridium difficile colitis and diarrhea. Intestinal tissue stimulated with C. difficile toxin A showed up-regulation of Cox-2 expression in lamina propria macrophages and elevated prostaglandin levels. Toxin A-stimulated loops exhibited severe inflammation and increased secretory volume. Celecoxib, a specific Cox-2 inhibitor, significantly reduced toxin A-induced prostaglandin production. Furthermore, celecoxib (greater than or equal to0.02 mg/mL) blocked both histologic damage (mean histologic grade, 1.25 vs. 3.44 in rabbits receiving toxin A alone; P < .0005) and secretion (volume: length ratio, 0.18 vs. 0.72 in those receiving toxin A alone; P = .002) in toxin A-stimulated loops in a dose-related manner. Thus, toxin A induced expression of Cox-2 in the host, and prostaglandins produced through Cox-2 were involved in the mediation of the increased secretion of electrolytes and water and the inflammatory response induced by toxin A.
引用
收藏
页码:648 / 652
页数:5
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