NFAT but not NF-kappa B is critical for transcriptional induction of the prosurvival gene A1 after IgE receptor activation in mast cells
- Author(s)
- Ulleras, E; Karlberg, M; Westerberg, CM; Alfredsson, J; Gerondakis, S; Strasser, A; Nilsson, G;
- Details
- Publication Year 2008-03-15,Volume 111,Issue #6,Page 3081-3089
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- 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.
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- BCL-2 FAMILY-MEMBER; FC-EPSILON-RI; INDUCED APOPTOSIS; MICE LACKING; CYTOKINE PRODUCTION; IMMUNE-RESPONSES; NUCLEAR-FACTOR; UP-REGULATION; TNF-ALPHA; T-CELLS
- Publisher's Version
- https://doi.org/10.1182/blood-2006-10-053371
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2008-03-15 12:00:00