Delphinidin activates NFAT and induces IL-2 production through SOCE in T cells.
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 Ca(2+) concentration by releasing Ca(2+) from intracellular stores and increasing Ca(2+) entry. The putative Ca(2+) release activated Ca(2+) (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.
Institute of Pharmacology and Morphophysiology, Universidad Austral de Chile, P.O. Box 567, Valdivia, Chile.
Evelyn
E
Jara
María A
MA
Hidalgo
Juan L
JL
Hancke
Alejandra I
AI
Hidalgo
Sebastian
S
Brauchi
Luisa
L
Nuñez
Carlos
C
Villalobos
Rafael A
RA
Burgos
D000813:Anilides / Q000494:pharmacology; D000872:Anthocyanins / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis*; D019169:Jurkat Cells; D050778:NFATC Transcription Factors / Q000378:metabolism*; D013324:Strontium / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism*; D013830:Thiadiazoles / Q000494:pharmacology
C476308:4-methyl-4'-(3,5-bis(trifluoromethyl)-1H-pyrazol-1-yl)-1,2,3-thiadiazole-5-carboxanilide; D000813:Anilides; D000872:Anthocyanins; D007376:Interleukin-2; D050778:NFATC Transcription Factors; D013830:Thiadiazoles; D005682:Gadolinium; C017185:delphinidin; D002118:Calcium; D013324:Strontium