期刊
PROSTAGLANDINS & OTHER LIPID MEDIATORS
卷 100, 期 -, 页码 22-29出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.prostaglandins.2013.01.003
关键词
Anandamide; Bimatoprost; Colitis; Prostamides
资金
- Broad Medical Research Program of The Broad Foundation [IBD-0268R]
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-alpha and IL-1 beta to elicit colitis-like tissue damage. The PGF(2 alpha)-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(2 alpha)-ethanolamide and PGE(2)-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. (C) 2013 Elsevier Inc. All rights reserved.
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