Differential Expression of Cannabinoid Receptors in the Human Colon: Cannabinoids Promote Epithelial Wound Healing

Abstract

CB1 receptors are expressed in normal human colon and colonic epithelium is responsive biochemically and functionally to cannabinoids. Increased epithelial CB2-receptor expression in human inflammatory bowel disease tissue implies an immunomodulatory role that may impact on mucosal immunity.

The endocannabinoid system in inflammatory bowel diseases: from pathophysiology to therapeutic opportunity

“…Indeed, cannabinoids such as anandamide, noladin ether, and arachidonoylcyclopropylamide (ACPA) induce wound-closure in human colonic epithelial cell lines, suggesting that delayed wound healing, a feature of IBD lesions, might be reversed by cannabinoids [34]. Additionally, in vitro studies suggest roles for both cannabinoid receptors in modulating inflammatory processes, including suppression of the activation of macrophages and mast cells, secretion of proinflammatory cytokines, and modulation of T helper lymphocytes by reducing the activated T cell population, inducing their apoptosis, and inhibiting their proliferation [33,[35][36][37][38][39][40].…”

“…The discrepancies, between human studies, in the inflammation-induced variation of expression of cannabinoid receptors (Table 1) could be explained by varying degrees of infiltration and mucosal remodeling or alteration as well as an analysis of different zones of the inflamed colon (ulcerations or at a distance from ulcerations). Indeed, in normal colonic tissue, CB 1 immunoreactivity is most evident on the microvillus border of the apical surface of the colonic epithelium, as well as the smooth muscle and the submucosal nerve bundles [34,54,60]. By contrast, CB 2 expression was more evident in subepithelial macrophages and plasmocytes characteristically present within the lamina propria of normal bowel, with no evident staining in the colonic epithelial border [34,54,60].…”

“…Indeed, in normal colonic tissue, CB 1 immunoreactivity is most evident on the microvillus border of the apical surface of the colonic epithelium, as well as the smooth muscle and the submucosal nerve bundles [34,54,60]. By contrast, CB 2 expression was more evident in subepithelial macrophages and plasmocytes characteristically present within the lamina propria of normal bowel, with no evident staining in the colonic epithelial border [34,54,60]. In acute phase IBD, CB 1 immunostaining was evident in the same structures as normal tissue, in contrast to CB 2 immunoreactivity which was also evident in the microvillus border.…”

Du cannabis aux agonistes sélectifs du récepteur CB2

“…Ainsi, l'activation des CB 2 R par un agoniste sélectif JWH-133 induirait une régres-sion tumorale (dans le modèle de cellules de gliomes C6 greffées à des souris nude athymiques) [35] ; elle serait responsable de l'action anti-angiogénique de ce composé dans les gliomes malins (via l'inhibition directe de la migration cellulaire endothéliale vasculaire et la diminution de l'expression des facteurs pro-angiogéniques VEGF [vascular endothelial growth factor] et angiopoïétine-2) [35] et favoriserait l'apoptose via la synthèse accrue de novo de céramide [3]. En effet, il a été montré que JWH-133, un agoniste sélectif du CB 2 R, diminue l'inflammation du côlon dans un modèle de colite induite par le dextran sulfate de sodium [22]. Malgré sa prédominance périphérique, le CB 2 R est également surexprimé dans les neurones et les cellules gliales lors d'une inflammation induite par les maladies neurodégénératives chroniques [2].…”

Long term cannabinoid receptor (CB1) blockade in obesity: Implications for the development of colorectal cancer

“…4 One major side effect of daily consumption of rimonabant (20 mg) is diarrhea, 4 and one mechanism for this effect is through CB1 antagonism/inverse agonism on enteric nerves, leading to an increase in gut motility. 5 We have reported that the CB1 receptor is normally expressed in the cytoplasm and luminal membrane of human intestinal epithelium, 6 and CB1 agonists have been shown to ameliorate disease severity in animal models of intestinal inflammation. 7 In our studies investigating the mechanism of CB1 and CB2 involvement in human Inflammatory Bowel Diseases (IBD), we have utilised a cell line derived from normal human colonic epithelium, NCM460 and the synthetic CB1 antagonist/inverse agonist, AM251 (Tocris, UK).…”