S1741 Expression of the Endocannabinoid System in Human Colonic Tissue: A Potencial Protective Role in Ulcerative Colitis

Abstract

INTRODUCTION: Recent studies suggest a potential role of the endocannabinoid system in motility regulation and gastrointestinal inflammation. CB1 receptor activation reduces gastrointestinal inflammation in several animal models. In addition, patients with inflammatory bowel disease (IBD) present an increase of CB2 receptor expression. However, the presence and function of the endocannabinoid system in IBD is not well characterized. AIMS & METHODS: Western Blot and Immunohistochemical analysis were performed to identify CB1 and CB2 receptors and synthesis and inactivation enzymes in untreated active pancolitis, at disease onset and after achieving remission, in comparison with normal human colonic tissue. 24 patients with a first ever flare of pancolitis (clinical, endoscopic and pathological criteria) were studied. In each patient rectal mucosal samples were obtained at first colonoscopy, before treatment (acute group), and after achieving clinical and endoscopic remission (quiescent group). 22 normal samples of colonic tissue from patients underwent colonic resections for colorectal cancer (at least 10 cm apart from the tumor) were also analyzed (control group). RESULTS: Western Blot and immunocytochemical analyses indicated that the endocannabinoid system was present in the colonic tissue, but showed a differential distribution in themucosal epithelium, lamina propria, smooth muscle and myenteric plexus. Quantification of epithelium immunoreactivity for each component of the endocannabinoid system showed: in acute group a significant increase of CB2 receptor and 2-AG pathway activity (DAGLa and MAGL) in mild and moderate pancolitis (Truelove and Witts score) compared to normal tissue (p<0.05). In contrast, NAPE-PLD was significantly decreased in acute group in moderate and severe pancolitis. Rest of components of endocannabinoid system does not show differences. In quiescent UC, we observed a recovery of CB2, DAGLa and NAPE-PLD expression levels, mainly in patients treated with 5-ASA and 5-ASA + corticoids. Additionally, it should be noted a significantly decrease of CB1 receptor in quiescent UC. Regarding lamina propria immune cells, in acute group we observed a significant rise of inactivation enzymes (FAAH and MAGL) in comparison with normal tissue (p<0.001). These levels turned to normality in quiescent UC (p<0.001). CONCLUSION: These data indicate that the CB2 receptor, throughout 2-AG signalling pathway,may represent a braking system for the pathophysiological mechanisms of Ulcerative Colitis. These results suggest that some drugs targeting the endocannabinoid system could be useful in treating IBD.