Upper airway epithelial cells support eosinophil survival in vitro throughproduction of GM-CSF and prostaglandin E-2: Regulation by glucocorticoids and TNF-alpha

Production of GM-CSF by epithelial cells has been implicated in eosinophil survival within the airways, although GM-CSF promotes neutrophil and monocy te survival as well. Using primary cultures of human airway epithelial cell s, we undertook a comprehensive examination of factors that enhance eosinop hil survival or apoptosis. Unstimulated epithelial cells were compared to e pithelial cells stimulated with TNF-alpha in the presence or absence of dex amethasone. A striking increase in survival was observed when peripheral bl ood eosinophils were cultured with supernatants derived from unstimulated a nd TNF-alpha-stimulated epithelial cells. Cultured epithelial cells were ex amined for transcripts of cytokines shown to enhance eosinophil survival (G M-CSF, IL-3, IL-5, IL-13, and IFN-gamma), and transcripts for cytokines pro moting apoptosis (IL-10 and TGF-beta). GM-CSF transcripts, but not the othe r 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 PGE(2) in epithelial cell supernatants and dexamethaso ne 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. Sel ectivity of GM-CSF for eosinophil versus neutrophil survival was demonstrat ed and suggests that epithelial cell regulation of GM-CSF and PGE(2) contri bute to eosinophil survival in vitro and may contribute to eosinophil accum ulation in allergic disease.