title: Prostaglandin ethanolamides attenuate damage in a human explant colitis model.
abstract: 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 PGF-ethanolamide analogue, bimatoprost decreased colitis scores which were reversed by a prostamide-specific antagonist AGN 211334, but not the FP receptor antagonist AL-8810. PGF-ethanolamide and PGE-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.
authors: Discipline of Pharmacology, School of Medical Sciences, Faculty of Health Sciences, The University of Adelaide, South Australia, Australia.
authors: Lauren L
authors: LL
authors: Nicotra
authors: Megan
authors: M
authors: Vu
authors: Benjamin S
authors: BS
authors: Harvey
authors: Scott D
authors: SD
authors: Smid
mesh_terms: D000328:Adult; D000577:Amides / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D000069580:Bimatoprost; D003008:Cloprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D003092:Colitis / Q000378:metabolism / Q000517:prevention & control*; D012809:Colon, Sigmoid / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015237:Dinoprost / Q000031:analogs & derivatives / Q000494:pharmacology; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D063388:Endocannabinoids / Q000494:pharmacology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053583:Interleukin-1beta / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D010080:Oxazoles / Q000494:pharmacology; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D055815:Young Adult
chemical_list: C523387:AGN 211334; D000577:Amides; D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D063388:Endocannabinoids; D053583:Interleukin-1beta; D010080:Oxazoles; D053284:Polyunsaturated Alkamides; D011982:Receptors, Prostaglandin; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; C107684:prostaglandin E2 ethanolamide; C121227:AL 8810; D003008:Cloprostenol; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone; D000069580:Bimatoprost; C078814:anandamide; C012655:nimesulide