EXPRESSION OF EOTAXIN BY HUMAN LUNG EPITHELIAL-CELLS - INDUCTION BY CYTOKINES AND INHIBITION BY GLUCOCORTICOIDS

Eotaxin is a potent and specific eosinophil chemoattractant that is mo bilized in the respiratory epithelium after allergic stimulation. Pulm onary levels of eotaxin mRNA are known to increase after allergen expo sure in sensitized animals. Pn this study we demonstrate that TNF alph a and IL-1 beta induce the accumulation of eotaxin mRNA in the pulmona ry epithelial cell lines A549 and BEAS 2B in a dose-dependent manner, Cytokine-induced A549 cell mRNA accumulation was maximal at 4 h and wa s significantly enhanced when the cells were costimulated with IFN gam ma. TNF alpha- and IL-1 beta-induced increases in eotaxin mRNA were di minished in a dose-dependent manner by the glucocorticoid dexamethason e and were augmented by the protein synthesis inhibitor cycloheximide. Cytokine-induced increases in eotaxin mRNA expression correlated with increased eotaxin protein production and secretion, and dexamethasone inhibition of cytokine-induced eotaxin mRNA augmentation was associat ed with diminished eotaxin protein secretion. These findings, together with the known kinetics of TNF alpha and IL-1 beta mobilization in as thmatic airways and the potent eosinophil chemotactic effects of eotax in, define a mechanism linking inflammatory cytokine mobilization to e osinophil recruitment that may be relevant to the pathogenesis of asth ma.