|
|
Blood, 15 March 2008, Vol. 111, No. 6, pp. 3081-3089.
Prepublished online as a Blood First Edition Paper on January 8, 2008; DOI 10.1182/blood-2006-10-053371.
 Previous Article | Table of Contents | Next Article 
IMMUNOBIOLOGY
NFAT but not NF- B is critical for transcriptional induction of the prosurvival gene A1 after IgE receptor activation in mast cells
Erik Ullerås1,2,
Mats Karlberg1,
Christine Möller Westerberg1,
Jessica Alfredsson1,
Steve Gerondakis3,
Andreas Strasser3, and
Gunnar Nilsson1
1 Clinical Immunology and Allergy Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden;
2 Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, Uppsala, Sweden; and
3 Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia
Fc RI-activation–induced survival of mast cells is dependent on the expression and function of the prosurvival protein A1. The expression of A1 in lymphocytes and monocytes has previously been described to be transcriptionally regulated by NF- B. Here we demonstrate that the expression of A1 in mast cells is not dependent on NF-B but that NFAT plays a crucial role. FcRI-induced A1 expression was not affected in mast cells overexpressing an IB- super-repressor or cells lacking NF-B subunits RelA, c-Rel, or c-Rel plus NF-B1 p50. In contrast, inhibition of calcineurin and NFAT by cyclosporin A abrogated the expression of A1 in mast cells on FcRI-activation but had no effect on lipopolysaccharide-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 FcRI 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 FcRI-stimulation. These results indicate that, in FcRI stimulated mast cells, A1 is transcriptionally regulated by NFAT1 but not by NF-B.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
| |
