Expression of the transcription factor NFAT2 in human neutrophils: IgE-dependent, Ca2+- and calcineurin-mediated NFAT2 activation.
NFAT (nuclear factors of activated T cells) proteins constitute a family of transcription factors involved in mediating signal transduction. The presence of NFAT isoforms has been described in all cell types of the immune system, with the exception of neutrophils. In the present work we report for the first time the expression in human neutrophils of NFAT2 mRNA and protein. We also report that specific antigens were able to promote NFAT2 protein translocation to the nucleus, an effect that was mimicked by the treatment of neutrophils with anti-immunoglobulin E (anti-IgE) or anti-Fcepsilon-receptor antibodies. Antigens, anti-IgE and anti-FcepsilonRs also increased Ca2+ release and the intracellular activity of calcineurin, which was able to interact physically with NFAT2, in parallel to eliciting an enhanced NFAT2 DNA-binding activity. In addition, specific chemical inhibitors of the NFAT pathway, such as cyclosporin A and VIVIT peptide, abolished antigen and anti-IgE-induced cyclooxygenase-2 (COX2) gene upregulation and prostaglandin (PGE(2)) release, suggesting that this process is through NFAT. Our results provide evidence that NFAT2 is constitutively expressed in human neutrophils, and after IgE-dependent activation operates as a transcription factor in the modulation of genes, such as COX2, during allergic inflammation.
Vega
Antonio
A
Servicio Regional de Inmunología y Alergia, Hospital Universitario Virgen Macarena, Sevilla, Spain.
Chacón
Pedro
P
Monteseirín
Javier
J
El Bekay
Rajaa
R
Alba
Gonzalo
G
Martín-Nieto
José
J
Sobrino
Francisco
F
D000328:Adult; D019703:Calcineurin / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism*; D014158:Transcription, Genetic
D050778:NFATC Transcription Factors; D007073:Immunoglobulin E; D051546:Cyclooxygenase 2; D019703:Calcineurin; D002118:Calcium