Cannabinoid Receptor-2 Ameliorates Inflammation in Murine Model of Crohn's Disease.
J Crohns Colitis
; 11(11): 1369-1380, 2017 Oct 27.
Article
in En
| MEDLINE
| ID: mdl-28981653
BACKGROUND AND AIMS: Cannabinoid receptor stimulation may have positive symptomatic effects on inflammatory bowel disease [IBD] patients through analgesic and anti-inflammatory effects. The cannabinoid 2 receptor [CB2R] is expressed primarily on immune cells, including CD4+ T cells, and is induced by active inflammation in both humans and mice. We therefore investigated the effect of targeting CB2R in a preclinical IBD model. METHODS: Employing a chronic ileitis model [TNFΔARE/+ mice], we assessed expression of the CB2R receptor in ileal tissue and on CD4+ T cells and evaluated the effect of stimulation with CB2R-selective ligand GP-1a both in vitro and in vivo. Additionally, we compared cannabinoid receptor expression in the ilea and colons of healthy human controls with that of Crohn's disease patients. RESULTS: Ileal expression of CB2R and the endocannabinoid anandamide [AEA] was increased in actively inflamed TNF∆ARE/+ mice compared with controls. CB2R mRNA was preferentially induced on regulatory T cells [Tregs] compared with T effector cells, approximately 2.4-fold in wild-type [WT] and 11-fold in TNF∆ARE/+ mice. Furthermore, GP-1a enhanced Treg suppressive function with a concomitant increase in IL-10 secretion. GP-1a attenuated murine ileitis, as demonstrated by improved histological scoring and decreased inflammatory cytokine expression. Lastly, CB2R is downregulated in both chronically inflamed TNF∆ARE/+ mice and in IBD patients. CONCLUSIONS: In summary, the endocannabinoid system is induced in murine ileitis but is downregulated in chronic murine and human intestinal inflammation, and CB2R activation attenuates murine ileitis, establishing an anti-inflammatory role of the endocannabinoid system.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Crohn Disease
/
Receptor, Cannabinoid, CB2
Type of study:
Observational_studies
/
Prognostic_studies
Limits:
Animals
/
Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
J Crohns Colitis
Journal subject:
GASTROENTEROLOGIA
Year:
2017
Document type:
Article
Affiliation country:
Estados Unidos
Country of publication:
Reino Unido