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Regulation of calcium signaling in dendritic cells by 1,25‐dihydroxyvitamin D 3
Author(s) -
Shumilina Ekaterina,
Xuan Nguyen Thi,
Matzner Nicole,
Bhandaru Madhuri,
Zemtsova Irina M.,
Lang Florian
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-142265
Subject(s) - chemistry , homeostasis , cd86 , stimulation , cytosol , microbiology and biotechnology , calcium , intracellular , antigen , calcium metabolism , biochemistry , endocrinology , biology , immunology , enzyme , gene , phenotype , organic chemistry
Dendritic cells (DCs) are antigen‐presenting cells that provide a link between innate and adaptive immunity. Ca 2+ ‐dependent signaling plays a central regulatory role in DC responses to diverse antigens. DCs are a primary target of 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ], a secosteroid hormone, that, in addition to its wellestablished action on Ca 2+ homeostasis, possesses immunomodulatory properties. Surprisingly, nothing is known about its effects on DC cytosolic Ca 2+ activity. The present study explored whether 1,25(OH) 2 D 3 modifies the intracellular Ca 2+ concentration ([Ca 2+ ] i ) in DCs. Here we show that mouse DCs expressed K + ‐independent (NCX1–3) and K + ‐dependent (NCKX1, 3, 4, and 5) Na + /Ca 2+ exchangers. Acute application of LPS (100 ng/ml) to DCs increased [Ca 2+ ] i , an effect significantly blunted by prior incubation with 1,25(OH) 2 D 3 . 1,25(OH) 2 D 3 increased the membrane abundance of the NCKX1 protein, up‐regulated the K + ‐ and Na + ‐dependent Ca 2+ entry and enhanced the K + ‐dependent Na + /Ca 2+ exchanger currents. The NCKX blocker 3′,4′‐dichlorobenzamyl (DBZ) reversed the inhibitory effect of 1,25(OH) 2 D 3 on the LPS‐induced increase of [Ca 2+ ] i . Expression of the costimulatory molecule CD86 was down‐regulated by 1,25(OH) 2 D 3 , an effect reversed by DBZ. In summary, 1,25(OH) 2 D 3 blunts the LPS‐induced increase in [Ca 2+ ] i by stimulation of Na + /Ca 2+ exchangerdependent Ca 2+ extrusion, an effect that contributes to 1,25(OH) 2 D 3 ‐mediated immunosuppression. The results disclose completely novel mechanisms in the regulation of DC maturation and function.—Shumilina, E., Xuan, N. T., Matzner, N., Bhandaru, M., Zemtsova, I. M., Lang, F. Regulation of calcium signaling in dendritic cells by 1,25‐dihydroxyvitamin D 3 . FASEB J. 24, 1989–1996 (2010). www.fasebj.org