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

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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 CB1 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 CB1 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.

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Acknowledgements

The authors are grateful to Dott. Vittorio Cosenza, AO Sorrento (Napoli). The technical help of Mr. C. Meccariello (Istituto di Scienze dell’ Alimentazione, Consiglio Nazionale delle Ricerche, Avellino, Italy) is also gratefully acknowledged. This work was partly supported by Epitech Italia S.r.l.

Competing interests

The authors declare no competing interests.

Author information

Authors and Affiliations

  1. Dipartimento di Gastroenterologia, Università di Napoli “Federico II”, Naples, Italy

    Giuseppe D’Argenio & Ilenia Grandone

  2. Endocannabinoid Research Group, Institute of Biomolecular Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli, Naples, Italy

    Stefania Petrosino, Marta Valenti & Vincenzo Di Marzo

  3. Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Fisciano, Italy

    Stefania Petrosino

  4. Istituto di Scienze dell’Alimentazione, Consiglio Nazionale delle Ricerche, Avellino, Italy

    Carmen Gianfrani & Giuseppe Mazzarella

  5. Gastroenterologia, A.O. “Rummo”, Benevento, Italy

    Giuseppe Scaglione & Italo Sorrentini

  6. Eicosanoid & Lipid Research Division, and Centre for Experimental Gynecology & Breast Research, University-Klinikum Benjamin Franklin, Free University Berlin, Berlin, Germany

    Santosh Nigam

Authors
  1. Giuseppe D’Argenio
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  2. Stefania Petrosino
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  3. Carmen Gianfrani
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  4. Marta Valenti
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  5. Giuseppe Scaglione
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  6. Ilenia Grandone
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  7. Santosh Nigam
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  8. Italo Sorrentini
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  9. Giuseppe Mazzarella
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  10. Vincenzo Di Marzo
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Correspondence to Vincenzo Di Marzo.

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D’Argenio, G., Petrosino, S., Gianfrani, C. et al. Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats. J Mol Med 85, 523–530 (2007). https://doi.org/10.1007/s00109-007-0192-3

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  • DOI: https://doi.org/10.1007/s00109-007-0192-3

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