Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats

• Published in: Journal of molecular medicine (Berlin, Germany) Vol. 85; no. 5; pp. 523 - 530
• Main Authors: D’Argenio, Giuseppe, Petrosino, Stefania, Gianfrani, Carmen, Valenti, Marta, Scaglione, Giuseppe, Grandone, Ilenia, Nigam, Santosh, Sorrentini, Italo, Mazzarella, Giuseppe, Di Marzo, Vincenzo
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.05.2007; Springer Nature B.V
• Subjects: 2-Arachidonoylglycerol; Adolescent; Adult; Amides; Anandamide; Animals; Arachidonic Acids - metabolism; Atrophy; Biological and medical sciences; Cannabinoid CB1 receptors; Cannabinoid Receptor Modulators - metabolism; Cannabinoids; Case-Control Studies; Celiac disease; Celiac Disease - chemically induced; Celiac Disease - diet therapy; Celiac Disease - metabolism; Celiac Disease - pathology; Child; Colitis; Diet, Protein-Restricted; Disease Models, Animal; Duodenum - metabolism; Duodenum - pathology; Endocannabinoid system; Endocannabinoids; Ethanolamines; Female; Gastroenterology. Liver. Pancreas. Abdomen; General aspects; Gluten; Glycerides - metabolism; Glycerol; Humans; Inflammatory bowel diseases; Intestine; Jejunum; Jejunum - metabolism; Jejunum - pathology; Male; Medical sciences; Methotrexate; Middle Aged; Mucosa; Other diseases. Semiology; Palmitic Acids - metabolism; Palmitoylethanolamide; Patients; Peroxidase; Peroxidase - metabolism; Polyunsaturated Alkamides - metabolism; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1 - metabolism; Remission; Remission (Medicine); Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Time Factors; Up-Regulation; Antineoplastic agent; Immunopathology; Rat; Rodentia; Inflammation; Cannabinoid; Coeliac disease; Antifolate; Atrophy; Medicine; Celiac disease; Vertebrata; Mammalia; Endogenous; Treatment; Antimetabolic; Endocannabinoid; Intestinal malabsorption; Animal; Intestinal inflammation; Digestive diseases; Intestinal disease; Methotrexate
• ISSN: 0946-2716; 1432-1440
• DOI: 10.1007/s00109-007-0192-3

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.