INHIBITION OF INTERLEUKIN-8 EXPRESSION BY DEXAMETHASONE IN HUMAN CULTURED AIRWAY EPITHELIAL-CELLS

Interleukin-8 (IL-8) is a neutrophil chemotactic factor expressed in m any cell types, including human airway epithelial cells (HAEC). Inhale d corticosteroids are now used increasingly early in the treatment of airway inflammation such as in asthma, and directly interact with HAEC at relatively high concentrations. We have investigated the effect of dexamethasone on IL-8 expression in primary cultured HAEC obtained fr om transplantation donors. Northern blot analysis was used to measure IL-8 mRNA levels in HAEC, and radioimmunoassay was used to measure IL- 8 protein in culture supernatant fluids. We demonstrated that IL-8 was expressed by primary cultured HAEC and that this was enhanced by IL-1 beta and tumour necrosis factor-alpha stimulation, but not by IL-6 or lipopolysaccharide. Dexamethasone suppressed IL-8 mRNA expression and protein synthesis dose-dependently in both resting and stimulated HAE C. The half-life of IL-8 mRNA determined in the presence of actinomyci n D was less than 1 hr, and dexamethasone preincubation had no effect on mRNA stability. These results support the view that HAEC may play a n important role in the pathogenesis of airway inflammatory diseases, and that glucocorticosteroids may exert their antiinflammatory effects by blocking IL-8 gene expression and generation in these cells.