Abstract
BackgroundRecent studies suggest potential roles of the endocannabinoid system in gastrointestinal inflammation. Although cannabinoid CB2 receptor expression is increased in inflammatory disorders, the presence and function of the remaining proteins of the endocannabinoid system in the colonic tissue is not well characterized.MethodologyCannabinoid CB1 and CB2 receptors, the enzymes for endocannabinoid biosynthesis DAGLα, DAGLβ and NAPE-PLD, and the endocannabinoid-degradating enzymes FAAH and MAGL were analysed in both acute untreated active ulcerative pancolitis and treated quiescent patients in comparison with healthy human colonic tissue by immunocytochemistry. Analyses were carried out according to clinical criteria, taking into account the severity at onset and treatment received.Principal FindingsWestern blot and immunocytochemistry indicated that the endocannabinoid system is present in the colonic tissue, but it shows a differential distribution in epithelium, lamina propria, smooth muscle and enteric plexi. Quantification of epithelial immunoreactivity showed an increase of CB2 receptor, DAGLα and MAGL expression, mainly in mild and moderate pancolitis patients. In contrast, NAPE-PLD expression decreased in moderate and severe pancolitis patients. During quiescent pancolitis, CB1, CB2 and DAGLα expression dropped, while NAPE-PLD expression rose, mainly in patients treated with 5-ASA or 5-ASA+corticosteroids. The number of immune cells containing MAGL and FAAH in the lamina propria increased in acute pancolitis patients, but dropped after treatment.ConclusionsEndocannabinoids signaling pathway, through CB2 receptor, may reduce colitis-associated inflammation suggesting a potential drugable target for the treatment of inflammatory bowel diseases.
Highlights
The endocannabinoid system (ECS) has been described in the gastrointestinal tract in the epithelial, immune and neural compartments
Components of ECS include cannabinoid CB1 and CB2 receptors, their endogenous lipid ligands (2-arachidony glycerol–2-AG; anandamide - AEA) and enzymes involved in their biosynthesis and release (DAGLa and DAGLb for 2-AG; NAPE-PLD for AEA)[10,11,12,13,14,15], as well as mechanisms for cellular uptake and degradation, such as fatty acid amide hydrolase (FAAH) for AEA and monoacylglycerol lipase (MAGL) for 2-AG.[16,17]
The role of endocannabinoids and its derivatives in Inflammatory Bowel Disease (IBD) is not completely known[18,19,20,21,22], cannabinoid CB1 receptors have been proposed to participate in the epithelial wound healing during intestinal inflammation.[1,2,3,4,20]
Summary
The endocannabinoid system (ECS) has been described in the gastrointestinal tract in the epithelial, immune and neural compartments. It is involved in many physiological and physiopathological actions (peristalsis/contraction, secretion, gastric emptying, emesis, satiety and immunomodulation/inflammation and pain).[1,2,3,4,5,6] ECS roles comprise main facets of the pathogenesis of Inflammatory Bowel Disease (IBD) in humans, a disease that is likely to result from multiple factors, especially a disregulation of intestinal immune system and an inappropriate response to comensal bacteria or other luminal antigens.[7,8,9]. Cannabinoid CB2 receptor expression is increased in inflammatory disorders, the presence and function of the remaining proteins of the endocannabinoid system in the colonic tissue is not well characterized
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
