Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
2019715 | Prostaglandins & Other Lipid Mediators | 2013 | 8 Pages |
Endocannabinoids are protective in animal colitis models. As endocannabinoids also form novel prostaglandin ethanolamides (prostamides) via COX-2, we investigated the effects of prostamides and other COX-2 mediators on tissue damage in an ex vivo human mucosal explant colitis model. Healthy human colonic mucosae were incubated with pro-inflammatory cytokines TNF-α and IL-1β to elicit colitis-like tissue damage. The PGF2α-ethanolamide analogue, bimatoprost decreased colitis scores which were reversed by a prostamide-specific antagonist AGN 211334, but not the FP receptor antagonist AL-8810. PGF2α-ethanolamide and PGE2-ethanolamide also reduced cytokine-evoked epithelial damage. Anandamide was protective in the explant colitis model; however COX-2 inhibition did not alter its effects, associated with a lack of COX-2 induction in explant mucosal tissue. These findings support an anti-inflammatory role for prostamides and endocannabinoids in the human colon.
► Cytokines evoke colitis-like mucosal damage in human colonic explant tissue. ► Both exogenous and endogenous prostamides inhibit mucosal damage. ► The synthetic prostamide bimatoprost reversibly inhibited mucosal damage. ► Anandamide was also protective, but not attributable to COX-2 metabolites. ► Prostamides and endocannabinoids are anti-inflammatory in the human colon.