Genetic ablation of the src kinase p59fynT exacerbates pulmonary inflammation in an allergic mouse model.
Am J Respir Cell Mol Biol
; 24(4): 469-74, 2001 Apr.
Article
em En
| MEDLINE
| ID: mdl-11306441
ABSTRACT
p59fynT is a protein tyrosine kinase in the src family that has been associated with and believed to function in the signaling of many receptors, including the T-cell receptor. A role for the kinase in antigen-driven pulmonary inflammation was examined using mice whose p59fynT gene had been genetically ablated. FynKO mice that were sensitized to ovalbumin exhibited a marked increase in bronchoalveolar lavage eosinophils and cytokines, including interleukin (IL)-4 and IL-5, relative to wild-type mice in response to antigen aerosol exposure. Ovalbumin-stimulated IL-5 production was also increased in cultured splenocytes derived from fynKO mice relative to wild-type mice, whereas interferon-gamma levels were unchanged. Diminished concanavalin A--stimulated IL-4 levels from fynKO splenocytes were consistent with reduced serum immunoglobulin (Ig)E levels observed in sensitized/saline aerosol-challenged animals and may reflect defective natural killer 1.1(+) T cell development. Normalization of IgE levels in sensitized fynKO mice relative to wild-type mice occurred after repeat antigen challenge, which suggests a secondary source of IL-4. Overall, these data demonstrate fyn is a negative regulator of allergic airway inflammation in mice because its absence promotes a shift to a T helper-2 phenotype that may reflect the kinase's role in T-cell receptor signaling.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pneumonia
/
Proteínas Proto-Oncogênicas
/
Quinases da Família src
/
Hipersensibilidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Am J Respir Cell Mol Biol
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos