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Research article2011Peer reviewed

Differential regulation of Nr4a subfamily nuclear receptors following mast cell activation

Lundequist, Anders; Calounova, Gabriela; Wensman, Helena; Rönnberg, Elin; Pejler, Gunnar

Abstract

The biological function of the Nr4a subfamily of nuclear receptors is only partially understood. Here we show for the fist time that mast cell (MC) activation processes involve the regulation of Nr4a factors. Exposure of murine bone marrow-derived MCs (BMMCs) to live bacteria causes a robust and selective upregulation of all Nr4a members (Nr4a1-Nr4a3). In response to purified LPS, strong upregulation of Nr4a3, but not of Nr4a1 or Nr4a2 was seen. Nr4a3 expression was also induced after the activation of BMMCs by IgE receptor cross-linking. Moreover, Nr4a expression was induced in activated human MCs. As shown by Western blot analysis, Nr4a phosphorylation was induced by IgE receptor cross-linking and calcium ionophore stimulation of BMMCs and LAD2 cells, respectively. By using various inhibitors of signaling pathways, Nr4a3 induction in BMMCs was shown to be strongly dependent on Go6976-sensitive kinases and partially dependent on the nuclear factor of activated T-cells (NFAT) pathway, while nuclear factor kappa-light-chain-enhancer of activated B cells (NFKB) inhibition failed to inhibit Nr4a3 expression in BMMCs. Together, these data reveal selective induction of Nr4a family members in activated MCs and implicate Nr4a family nuclear receptors in the regulation of MC function. (C) 2011 Elsevier Ltd. All rights reserved.

Keywords

Mast cells; Nuclear receptors; Nr4a; IgE receptor cross-linking; Protein kinase C

Published in

Molecular Immunology
2011, Volume: 48, number: 15-16, pages: 1753-1761
Publisher: PERGAMON-ELSEVIER SCIENCE LTD