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.
Highlights
Cannabinoid receptors (CBR) belong to the large superfamily of heptahelical Gi/o protein coupled receptors [1]
In keeping with the Quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) results, Enzyme-linked immunosorbent assay (ELISA) analysis revealed an higher expression of CB1 protein in untreated celiac disease (UCD) patients with respect to control subjects (CS) (p,0.05), and lower CB1 protein levels in treated celiac disease (TCD) patients compared with UCD subjects (p,0.01)
We reported that the ex vivo incubation of treated celiac biopsies with PT-gliadin significantly increased the expression of mRNA and protein of both receptors
Summary
Cannabinoid receptors (CBR) belong to the large superfamily of heptahelical Gi/o protein coupled receptors [1]. High AEA levels in the duodenal mucosa of untreated celiac disease (UCD) patients in comparison to treated celiac disease (TCD) patients and control subjects (CS) [11] are likely due to an altered N-acylphosphatidyl-ethanolamine specific phospholipase D (NAPE-PLD) activity [12], and might self-induce an increase of CBR, as a fine mechanism of regulation common to many diseases [11,13,14]. Immunofluorescence analyses showed that CB1 protein is strongly expressed in duodenum biopsies from UCD patients [11], whereas CB2 is upregulated, both at transcriptional and translational levels, in small bowel biopsies obtained from children with celiac disease [15]. We investigated CBR mRNA and protein as well as functional activity levels in the duodenal mucosa of UCD and TCD patients, and CS. We explored the effect of the peptic-tryptic digest of gliadin (PT-gliadin) on CBR expression in organ culture biopsies taken from TCD patients
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