Altered expression of type-1 and type-2 cannabinoid receptors in celiac disease

Natalia Battista; Antonio Di Sabatino; Monia Di Tommaso; Paolo Biancheri; Cinzia Rapino; Paolo Giuffrida; Cinzia Papadia; Chiara Montana; Alessandra Pasini; Alessandro Vanoli; Francesco Lanzarotto; Vincenzo Villanacci; Gino R Corazza; Mauro Maccarrone

doi:10.1371/journal.pone.0062078

Altered expression of type-1 and type-2 cannabinoid receptors in celiac disease

PLoS One. 2013 Apr 19;8(4):e62078. doi: 10.1371/journal.pone.0062078. Print 2013.

Authors

Natalia Battista¹, Antonio Di Sabatino, Monia Di Tommaso, Paolo Biancheri, Cinzia Rapino, Paolo Giuffrida, Cinzia Papadia, Chiara Montana, Alessandra Pasini, Alessandro Vanoli, Francesco Lanzarotto, Vincenzo Villanacci, Gino R Corazza, Mauro Maccarrone

Affiliation

¹ Department of Biomedical Sciences, University of Teramo, Teramo, Italy. nbattista@unite.it

Abstract

Anandamide (AEA) is the prominent member of the endocannabinoid family and its biological action is mediated through the binding to both type-1 (CB1) and type-2 (CB2) cannabinoid receptors (CBR). The presence of AEA and CBR in the gastrointestinal tract highlighted their pathophysiological role in several gut diseases, including celiac disease. Here, we aimed to investigate the expression of CBR at transcriptional and translational levels in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also biopsies from treated celiac patients cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our data show higher levels of both CB1 and CB2 receptors during active disease and normal CBR levels in treated celiac patients. In conclusion, we demonstrate an up-regulation of CB1 and CB2 mRNA and protein expression, that points to the therapeutic potential of targeting CBR in patients with celiac disease.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Celiac Disease / drug therapy
Celiac Disease / genetics
Celiac Disease / metabolism*
Celiac Disease / pathology
Female
Fluorescent Antibody Technique
Gene Expression Regulation / drug effects
Gliadin / pharmacology
Humans
Intestinal Mucosa / drug effects
Intestinal Mucosa / metabolism
Intestinal Mucosa / pathology
Male
Microscopy, Confocal
Protein Binding / drug effects
RNA, Messenger / genetics
RNA, Messenger / metabolism
Receptor, Cannabinoid, CB1 / genetics
Receptor, Cannabinoid, CB1 / metabolism*
Receptor, Cannabinoid, CB2 / genetics
Receptor, Cannabinoid, CB2 / metabolism*

Substances

RNA, Messenger
Receptor, Cannabinoid, CB1
Receptor, Cannabinoid, CB2
Gliadin

Grants and funding

This project was partly supported by the Associazione Italiana Celiachia to GRC, and by Fondazione TERCAS (2009-2012 project) to MM. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.