Upper Airway Epithelial Cells Support Eosinophil Survival in vitro through Production of GM-CSF and Prostaglandin E2: Regulation by Glucocorticoids and TNF-α
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-α 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-α-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-), and transcripts for cytokines promoting apoptosis (IL-10 and TGF-(). GM-CSF transcripts, but not the other cytokines, were present in unstimulated epithelial cells, and levels were increased with TNF-α stimulation. TNF-α stimulation increased the levels of GM-CSF and PGE2 in epithelial cell supernatants and dexamethasone suppressed the TNF-α induced increases. The survival effects of the TNF-α-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.
Document Type: Research Article
Publication date: July 1, 1999
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- Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.
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