Back to Program | 2010 Program and Abstracts Overview | 2010 Posters

Pro-inflammatory cytokines cause damage in the gastrointestinal epithelial barrier, leading to increased translocation of luminal antigens and toxins. The ability to modulate the intestinal permeability during the inflammatory process could be important in devising future therapeutic strategies. Cannabinoids have previously been shown to also exert anti-inflammatory actions in the gut, therefore the aim of the present study was to examine whether cannabinoids modulate intestinal permeability during inflammationCaco-2 cells were grown until fully confluent on inserts in 12-well plates. Cells were treated with 10ng/ml of INF-γ for 8 h and 10ng/ml TNF-α for a further 16 hours. Transepithelial electrical resistance (TEER) measurements were made as a measure of permeability for the following 72 h (until TEER had recovered to baseline). The effects of cannabinoids on TEER during inflammation were assessed. Potential target sites of action were investigated using the following (all 1 µM); AM251 (CB1 receptor antagonist), AM630 (CB2 receptor antagonist), capsazepine (TRPV1 antagonist), GW9662 (PPARγ antagonist), GW6471 (PPARα antagonist), and O-1918 (proposed endothelial cannabinoid receptor antagonist). Data were analysed by one-way ANOVA and Dunnett’s post hoc test, and are reported as mean ± S.E.M.Cytokine treatment caused a fall in TEER (indicating an increase in cell permeability) of approx 20% after 24h. Phytocannabinoids significantly enhanced the recovery of cytokines-induced reduced TEER in a concentration dependent manner (Area under the curve (AUC); vehicle 1062 +/- 153; 10 μM delta-9-hydrocannabinol (THC) 263 +/- 53, P<0.01; 10 μM cannabidiol (CBD) 309 +/- 30, P<0.01). By contrast, endocannabinoids caused a further fall in TEER during inflammation in a concentration-dependent manner (AUC; vehicle 910 +/- 40; 10 μM anandamide 1522 +/- 111, P <0.05; 10 μM 2-arachidonoylglycerol (2-AG) 1343 +/- 79, P <0.05). Only CB1 receptor antagonism inhibited the actions of cannabinoids during inflammation in Caco-2 cells (THC P <0.05; CBD P <0.01, anandamide P<0.001; 2-AG P <0.01). These findings suggest that endocannabinoids may play a role in modulating intestinal permeability during the inflammatory process, and that phytocannabinoids may have therapeutic potential in the treatment of gastrointestinal disorders associated with a 'leaky' gut.