9th Annual BMRP Investigator Meeting - Abstract
Prostamide and Cannabinoid CB2 Receptors Attenuate Colitis in a Human Explant Model
Scott Smida, Lauren Nicotra, Ben Harvey and Megan Vu
Discipline of Pharmacology, Faculty of Health Sciences, The University of Adelaide (Adelaide, South Australia, Australia)
The endogenous cannabinoid system (ECS) reduces inflammation in animal models of colitis. Endocannabinoids are also substrates for an alternate pathway of metabolism via COX-2, forming prostaglandin ethanolamides (prostamides). The biological roles of the prostamides have not been characterized, but may be important in the pathology of IBD where the expression of both the ECS and COX-2 is elevated. We investigated the effects of cannabinoid receptor-selective ligands and endocannabinoids, including their COX-2 metabolites on colitis outcomes in an ex vivo human explant model. Healthy full thickness bowel tissue was obtained, mucosa dissected and placed in carbogenated culture medium at 37°C for 20hrs. Mucosal damage was generated via co-incubation with pro-inflammatory cytokines TNF-α and IL1β, which produced mucosal denudation, crypt loss and increased lamina propria lymphocyte numbers that was prevented with hydrocortisone co-incubation. Both the prostamide analogue bimatoprost and the cannabinoid CB2 receptor-selective agonist JWH-015 reduced colitis scores, which were reversible in the presence of a prostamide antagonist and CB2 antagonist JTE-907 respectively. The endogenous cannabinoid anandamide also reduced colitis scores. However this was not affected by a CB1 receptor antagonist AM251 or by the COX-2 inhibitor nimesulide. These results suggest an anti-inflammatory role for exogenous prostamides and CB2 receptors in an acute human explant colitis model.
a Principal Investigator