Cannabinoid CB2 receptor activation attenuates cytokine-evoked mucosal damage in a human colonic explant model without changing epithelial permeability

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dc.contributor.authorHarvey, B.
dc.contributor.authorNicotra, L.
dc.contributor.authorVu, M.
dc.contributor.authorSmid, S.
dc.date.issued2013
dc.description.abstractCannabinoid receptor activation is protective in animal colitis models. We sought to investigate if cannabinoids attenuated colitis-like tissue damage in human colonic specimens, with the hypothesis that cannabinoids would be protective in a cytokine-driven model of human colonic mucosal damage. Healthy human colonic mucosa was incubated with pro-inflammatory cytokines TNF-α and IL-1β to elicit colitis-like tissue damage. The cytokine-driven increase in scored crypt and mucosal damage and lymphocyte density was attenuated with concomitant hydrocortisone pretreatment. The cannabinoid receptor 2 (CB2) receptor-selective agonist JWH-015 significantly reduced colitis scores following cytokine incubation, as evidenced by a reduction in mucosal crypt and luminal epithelial damage and lymphocyte density in the lamina propria. The effect of JWH-015 was reversed in the presence of the CB2 receptor inverse agonist JTE-907. Anandamide was also protective in the cytokine-incubated explant colitis model in a manner reversible with JTE-907, while CB1 receptor agonism with ACEA was without effect. TNF-α and IL-1β together evoked an increase in paracellular epithelial permeability in Caco-2 cell monolayers over 48h of incubation. However, neither CB2 nor CB1 receptor activation altered the cytokine-evoked increase in permeability. These findings support a discrete role for CB2 receptors in the attenuation of detrimental pro-inflammatory cytokine-mediated mucosal damage in the human colon without directly affecting mucosal epithelial barrier function.
dc.description.statementofresponsibilityB.S. Harvey, L.L. Nicotra, M. Vu, S.D. Smid
dc.identifier.citationCytokine, 2013; 63(2):209-217
dc.identifier.doi10.1016/j.cyto.2013.04.032
dc.identifier.issn1096-0023
dc.identifier.issn1043-4666
dc.identifier.orcidSmid, S. [0000-0003-4192-7219]
dc.identifier.urihttp://hdl.handle.net/2440/79293
dc.language.isoen
dc.publisherAcademic Press
dc.rightsCrown copyright © 2013
dc.source.urihttps://doi.org/10.1016/j.cyto.2013.04.032
dc.subjectAnandamide
dc.subjectCannabinoid
dc.subjectColitis
dc.subjectEpithelial permeability
dc.subjectMucosal
dc.titleCannabinoid CB2 receptor activation attenuates cytokine-evoked mucosal damage in a human colonic explant model without changing epithelial permeability
dc.typeJournal article
pubs.publication-statusPublished

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