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Nuclear factor κB is activated in small intestinal mucosa of celiac patients

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Abstract

NF-κB regulates inflammatory and immune response by increasing the expression of specific genes. In celiac disease proinflammatory cytokines, adhesion molecules, and enzymes whose gene expression is known to be regulated by NF-κB are involved. This study investigated the activation of NF-κB in inflamed mucosa from patients with untreated celiac disease. Biopsy specimens from control, untreated, and treated patients were subjected to molecular biology analysis. NF-κB activation was evaluated by electrophoretic mobility shift assay. NF-κB related subunit protein level, and inducible nitric oxide synthase and cyclo-oxygenase 2 protein expression was analyzed by western blot. Both NF-κB/DNA binding activity and p50/p65 nuclear levels were higher in biopsy specimens from untreated patients than in those from treated patients and controls. The degradation of IκBβ in the cytosol and the reappearance in the nucleus indicated a persistent NF-κB activation in celiac disease. NF-κB activity was maintained in cultured biopsy specimens up to 6 h and decreased at 24 h, and then the addition of peptic-tryptic digest of gliadin caused the recovery of NF-κB activity at 6 h. NF-κB/DNA binding activity was correlated with inducible nitric oxide synthase and cyclo-oxygenase-2 protein expression. These results show for the first time that NF-κB is activated in the inflamed mucosa of celiac patients and suggest that it may represent a molecular target for the modulation of inflammatory response in celiac disease.

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Abbreviations

CD :

Celiac disease

COX :

Cyclo-oxygenase

iNOS :

Inducible nitric oxide synthase

IκB :

Inhibitory protein κB

NF-κB :

Nuclear factor κB

Pt-G :

Peptic-tryptic digest of gliadin

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Acknowledgements

This research was supported by a grant from the Italian government (PRIN 2002).

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Authors and Affiliations

  1. Department of Experimental Pharmacology, University of Naples Federico II, Via Domenico Montesano 49, 80131, Naples, Italy

    Maria Chiara Maiuri, Daniela De Stefano, Guido Mele & Rosa Carnuccio

  2. Department of Pediatrics and European Laboratory for the Investigation of Food-Induced Diseases, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy

    Simona Fecarotta, Luigi Greco & Riccardo Troncone

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  1. Maria Chiara Maiuri
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  2. Daniela De Stefano
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  3. Guido Mele
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  4. Simona Fecarotta
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  6. Riccardo Troncone
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  7. Rosa Carnuccio
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Correspondence to Rosa Carnuccio.

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Maiuri, M.C., De Stefano, D., Mele, G. et al. Nuclear factor κB is activated in small intestinal mucosa of celiac patients. J Mol Med 81, 373–379 (2003). https://doi.org/10.1007/s00109-003-0440-0

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  • DOI: https://doi.org/10.1007/s00109-003-0440-0

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