Journal of Physiology and Biochemistry

, Volume 66, Issue 2, pp 153–159

Gliadins induce TNFα production through cAMP-dependent protein kinase A activation in intestinal cells (Caco-2)

  • José Moisés Laparra Llopis
  • Yolanda Sanz Herranz
Original Paper

DOI: 10.1007/s13105-010-0020-z

Cite this article as:
Laparra Llopis, J.M. & Sanz Herranz, Y. J Physiol Biochem (2010) 66: 153. doi:10.1007/s13105-010-0020-z


Celiac disease is an autoimmune enteropathy caused by a permanent intolerance to gliadins. In this study the effects of two gliadin-derived peptides (PA2, PQPQLPYPQPQLP and PA9, QLQPFPQPQLPY) on TNFα production by intestinal epithelial cells (Caco-2) and whether these effects were related to protein kinase A (PKA) and/or -C (PKC) activities have been evaluated. Caco-2 cell cultures were challenged with several sets of gliadin peptides solutions (0.25 mg/mL), with/without different activators of PKA or PKC, bradykinin (Brdkn) and pyrrolidine dithiocarbamate (PDTC). The gliadin-derived peptides assayed represent the two major immunodominant epitopes of the peptide 33-mer of α-gliadin (56–88) (LQLQPFPQPQLPYPQPQLPYPQPQLPYPQPQPF). Both peptides induced the TNFα production triggering the inflammatory cell responses, the PA2 being more effective. The addition of the peptides in the presence of dibutyril cyclic AMP (cAMP), Brdkn or PDTC, inhibited the TNFα production. The PKC-activator phorbol 12-myristate 13-diacetate additionally increased the PA2- and PA9-induced TNFα production. These results link the gliadin-derived peptides induced TNFα production through cAMP-dependent PKA activation, where ion channels controlling calcium influx into cells could play a protective role, and requires NF-κB activation.


Celiac disease Gliadin Caco-2 TNFα Protein kinase A 

Copyright information

© University of Navarra 2010

Authors and Affiliations

  • José Moisés Laparra Llopis
    • 1
  • Yolanda Sanz Herranz
    • 1
  1. 1.Microbial Ecophysiology and Nutrition GroupInstituto de Agroquímica y Tecnología de Alimentos (CSIC)BurjassotSpain

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