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Delphinidin Activates NFAT and Induces IL-2 Production Through SOCE in T Cells

Cell Biochemistry and Biophysics volume 68, pages 497–509 (2014)Cite this article

Abstract

Delphinidin is an anthocyanidin that possesses antioxidant and anti-inflammatory effects; however, some reports suggest that delphinidin has pro-inflammatory properties. For this reason, we assessed the effect of delphinidin on cytokine production in T cells. We demonstrated that delphinidin increased the cytosolic-free Ca2+ concentration by releasing Ca2+ from intracellular stores and increasing Ca2+ entry. The putative Ca2+ release activated Ca2+ (CRAC) channel inhibitors BTP2 and gadolinium reduced the calcium entry stimulated by the anthocyanidin. Delphinidin induced nuclear factor of activated T cells (NFAT) translocation and NFAT-Luc activity in Jurkat cells and was dependent on the CRAC channel and calcineurin pathway. Delphinidin increased the mRNA expression and production of IL-2 in Jurkat cells and was inhibited by BTP2 and cyclosporine A. Using peripheral blood lymphocytes, we demonstrated that delphinidin increased the production of IL-2 and IFN-γ and was inhibited by BTP2. Taken together, our results suggest that delphinidin exerts immunostimulatory effects on T cells by increasing cytokine production through CRAC channel and NFAT activation.

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Abbreviations

SOCE:

Store-operated calcium entry

BTP2:

N-(4-[3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl]phenyl)-4-methyl-1,2,3-thiadiazole-5-carboxamide

CRAC:

Ca2+ release-activated Ca2+

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Acknowledgments

This work was supported by Grants from Consorcio de Tecnología e Innovación para la Salud CTI-Salud (CTE-06), Chile (CONICYT 21090900 and CONICYT AT-24100037).

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Affiliations

  1. Institute of Pharmacology and Morphophysiology, Universidad Austral de Chile, P.O. Box 567, Valdivia, Chile

    Evelyn Jara, María A. Hidalgo, Juan L. Hancke, Alejandra I. Hidalgo & Rafael A. Burgos

  2. Institute of Physiology, Faculty of Medicine, Universidad Austral de Chile, Valdivia, Chile

    Sebastian Brauchi

  3. Spanish Research Council, Institute of Molecular Biology and Genetics, University of Valladolid, Valladolid, Spain

    Luisa Nuñez & Carlos Villalobos

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  1. Evelyn Jara
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  2. María A. Hidalgo
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Correspondence to Rafael A. Burgos.

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Jara, E., Hidalgo, M.A., Hancke, J.L. et al. Delphinidin Activates NFAT and Induces IL-2 Production Through SOCE in T Cells. Cell Biochem Biophys 68, 497–509 (2014). https://doi.org/10.1007/s12013-013-9728-z

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Keywords

  • Delphinidin
  • Calcium
  • T cells
  • NFAT
  • Cytokines