Upper airway epithelial cells support eosinophil survival in vitro through production of GM-CSF and prostaglandin E2: regulation by glucocorticoids and TNF-alpha.
Allergy Asthma Proc
; 20(4): 243-53, 1999.
Article
em En
| MEDLINE
| ID: mdl-10476324
ABSTRACT
Production of GM-CSF by epithelial cells has been implicated in eosinophil survival within the airways, although GM-CSF promotes neutrophil and monocyte survival as well. Using primary cultures of human airway epithelial cells, we undertook a comprehensive examination of factors that enhance eosinophil survival or apoptosis. Unstimulated epithelial cells were compared to epithelial cells stimulated with TNF-alpha in the presence or absence of dexamethasone. A striking increase in survival was observed when peripheral blood eosinophils were cultured with supernatants derived from unstimulated and TNF-alpha-stimulated epithelial cells. Cultured epithelial cells were examined for transcripts of cytokines shown to enhance eosinophil survival (GM-CSF, IL-3, IL-5, IL-13, and IFN-gamma), and transcripts for cytokines promoting apoptosis (IL-10 and TGF-beta). GM-CSF transcripts, but not the other cytokines, were present in unstimulated epithelial cells, and levels were increased with TNF-alpha stimulation. TNF-alpha stimulation increased the levels of GM-CSF and PGE2 in epithelial cell supernatants and dexamethasone suppressed the TNF-alpha induced increases. The survival effects of the TNF-alpha-stimulated supernatants were effectively blocked by neutralizing antibodies to GM-CSF or by dexamethasone treatment of epithelial cells. Selectivity of GM-CSF for eosinophil versus neutrophil survival was demonstrated and suggests that epithelial cell regulation of GM-CSF and PGE2 contribute to eosinophil survival in vitro and may contribute to eosinophil accumulation in allergic disease.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sistema Respiratório
/
Dinoprostona
/
Fator Estimulador de Colônias de Granulócitos e Macrófagos
/
Fator de Necrose Tumoral alfa
/
Eosinófilos
/
Glucocorticoides
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Revista:
Allergy Asthma Proc
Ano de publicação:
1999
Tipo de documento:
Article