W1699 Toll-Like Receptor mRNA Expression Is Selectively Increased in the Colonic Mucosa of Two Animal Models of Chronic Stress: Relevance to Irritable Bowel Syndrome

G A A b st ra ct s reported to be reduced in UC. SERT knockout (KO), therefore, provides a gain-of-function model to test the role of 5-HT in the pathophysiology of intestinal inflammation. Dextran sodium sulfate (DSS; 3%) was included in the drinking water of wild-type C57/Bl6 mice and their transgenic SERT KO littermates for 7 days to induce colitis. The severity of colitis in SERT KO mice was significantly greater than that in their WT littermates. Body weight reduction, clinical scores, neutrophil infiltration, and mucosal ulcerations were all significantly greater in SERT KO animals; moreover, 50 % of transcripts encoding 70 prominent proinflammatory pathway-related genes (cytokines, interleukins, chemokines and their receptors), assayed by RT-PCR microarray, were also significantly more abundant in the SERT KO mice. Although these observations must still be confirmed in other models of inflammation and in a loss-of-function paradigm, these data are consistent with the hypothesis that 5-HT contributes to the severity of inflammation of the colon. The downregulation of SERT in UC may thus increase the severity of the condition as well as the abnormal intestinal motility and visceral hypersensitivity that accompany it.