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Ulcerative colitis induces changes on the expression of the endocannabinoid system in the human colonic tissue.
BACKGROUNDRecent studies suggest potential roles of the endocannabinoid system in gastrointestinal inflammation. Although cannabinoid CB(2) 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 CB(1) and CB(2) receptors, the enzymes for endocannabinoid biosynthesis DAGLalpha, DAGLbeta 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 CB(2) receptor, DAGLalpha 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, CB(1), CB(2) and DAGLalpha 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 CB(2) receptor, may reduce colitis-associated inflammation suggesting a potential drugable target for the treatment of inflammatory bowel diseases.
Department of Gastroenterology, Hospital del Mar, Universidad Autónoma, Barcelona, Spain., , , ,
PloS one 4:9 2009 pg e6893
Cannabinoid Receptor Modulators
Gene Expression Regulation
Pub Type(s)Journal Article
Research Support, Non-U.S. Gov't