Mechanism of dexamethasone-mediated interleukin-8 gene suppression in cultured airway epithelial cells

The effects of dexamethasone, a glucocorticoid analog, on interleukin 8 (IL -8) gene expression were studied in cultures of primary human tracheobronch ial epithelial cells and an immortalized human bronchial epithelial cell li ne, HBE1 cells. Dexamethasone inhibited IL-8 mRNA and protein expression in a concentration- and time-dependent manner. The inhibition did not occur a t the transcriptional level since both nuclear run-on activity and IL-8 pro moter-reporter gene expression assay revealed no significant effect. Instea d, there was a change in IL-8 mRNA stability in dexamethasone-treated cultu res. Under actinomycin D treatment, IL-8 mRNA was quite stable in dexametha sone-depleted cultures, while in dexamethasone-pretreated cultures, IL-8 me ssage was rapidly degraded within the first hour, then leveled off. When de xamethasone and actinomycin D were added simultaneously to dexamethasone-de pleted cultures, IL-8 mRNA remained rather stable. When cycloheximide was u sed to inhibit new protein synthesis, dexamethasone-dependent inhibition wa s not observed. These results suggest that a posttranscriptional mechanism, which requires dexamethasone-dependent new protein synthesis, is involved in the regulation of IL-8 mRNA by dexamethasone in airway epithelial cells.