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Research article2008Peer reviewedOpen access

NFAT but not NF-kappa B is critical for transcriptional induction of the prosurvival gene A1 after IgE receptor activation in mast cells

Ulleras, Erik; Karlberg, Mats; Westerberg, Christine Moller; Alfredsson, Jessica; Gerondakis, Steve; Strasser, Andreas; Nilsson, Gunnar

Abstract

FC is an element of RI-activation-induced survival of mast cells is dependent on the expression and function of the prosurvival protein A1. The expression of A 1 in lymphocytes and monocytes has previously been described to be transcriptionally regulated by NF-kappa B. Here we demonstrate that the expression of A1 in mast cells is not dependent on NF-kappa B but that NFAT plays a crucial role. FC is an element of RI-induced A1 expression was not affected in mast cells overexpressing an I kappa B-alpha super-repressor or cells lacking NF-kappa B subunits ReIA, c-Rel, or c-Rel plus NF-kappa B1 p50. In contrast, inhibition of calcineurin and NFAT by cyclosporin A abrogated the expression of A1 in mast cells on FC is an element of RI-activation but had no effect on lipopolysaccharicle-induced expression of A1 in J774A.1 monocytic cells. Cyclosporin A also inhibited luciferase expression in an A1 promoter reporter assay. A putative NFAT binding site in the A1 promoter showed inducible protein binding after FC is an element of RI crosslinking or treatment with ionomycin as detected in a band shift assay or chromatin immunoprecipitation. The binding protein was identified as NFAT1. Finally, mast cells expressing constitutively active NFAT1 exhibit increased expression of A1 after FC is an element of RI-stimulation. These results indicate that, in FC is an element of RI stimulated mast cells, A1 is transcriptionally regulated by NFAT1 but not by NF-kappa B.

Published in

Blood
2008, Volume: 111, number: 6, pages: 3081-3089
Publisher: AMER SOC HEMATOLOGY

    UKÄ Subject classification

    Genetics

    Publication identifier

    DOI: https://doi.org/10.1182/blood-2006-10-053371

    Permanent link to this page (URI)

    https://res.slu.se/id/publ/19206