title: Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats.
abstract: The endocannabinoid system is upregulated in both human inflammatory bowel diseases and experimental models of colitis. In this study, we investigated whether this upregulation is a marker also of celiac disease-induced atrophy. The levels of the cannabinoid CB(1) receptor, of the endocannabinoids, anandamide, and 2-arachidonoyl-glycerol (2-AG), and of the anti-inflammatory mediator palmitoylethanolamide (PEA) were analyzed in bioptic samples from the duodenal mucosa of celiac patients at first diagnosis assessed by the determination of antiendomysial antibodies and histological examination. Samples were analyzed during the active phase of atrophy and after remission and compared to control samples from non-celiac patients. The levels of anandamide and PEA were significantly elevated (approx. 2- and 1.8-fold, respectively) in active celiac patients and so were those of CB(1) receptors. Anandamide levels returned to normal after remission with a gluten-free diet. We also analyzed endocannabinoid and PEA levels in the jejunum of rats 2, 3, and 7 days after treatment with methotrexate, which causes inflammatory features (assessed by histopathological analyses and myeloperoxidase activity) similar to those of celiac patients. In both muscle/serosa and mucosa layers, the levels of anandamide, 2-AG, and PEA peaked 3 days after treatment and returned to basal levels at remission, 7 days after treatment. Thus, intestinal endocannabinoid levels peak with atrophy and regress with remission in both celiac patients and methotrexate-treated rats. The latter might be used as a model to study the role of the endocannabinoid system in celiac disease.
authors.affiliation: Dipartimento di Gastroenterologia, Università di Napoli Federico II, Naples, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Argenio
authors.forename: Stefania
authors.initials: S
authors.lastname: Petrosino
authors.forename: Carmen
authors.initials: C
authors.lastname: Gianfrani
authors.forename: Marta
authors.initials: M
authors.lastname: Valenti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Scaglione
authors.forename: Ilenia
authors.initials: I
authors.lastname: Grandone
authors.forename: Santosh
authors.initials: S
authors.lastname: Nigam
authors.forename: Italo
authors.initials: I
authors.lastname: Sorrentini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Mazzarella
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Di Marzo
mesh_terms: D000293:Adolescent; D000328:Adult; D000577:Amides; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D001284:Atrophy; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism*; D016022:Case-Control Studies; D002446:Celiac Disease / Q000139:chemically induced / Q000178:diet therapy / Q000378:metabolism* / Q000473:pathology; D002648:Child; D018753:Diet, Protein-Restricted; D004195:Disease Models, Animal; D004386:Duodenum / Q000378:metabolism* / Q000473:pathology; D063388:Endocannabinoids; D004983:Ethanolamines; D005260:Female; D005989:Glycerides / Q000378:metabolism; D006801:Humans; D007583:Jejunum / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008727:Methotrexate; D008875:Middle Aged; D010169:Palmitic Acids / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D000577:Amides; D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D004983:Ethanolamines; D005989:Glycerides; D010169:Palmitic Acids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; C005958:palmidrol; C094503:glyceryl 2-arachidonate; D009195:Peroxidase; C078814:anandamide; D008727:Methotrexate