Secretory leukocyte protease inhibitor (SLPI) is the predominant antiprotease of the conducting airways and may play a role in reducing airway inflammation. In this study, the effect of corticosteroids used in the treatment of inflammatory airway disease on SLPI transcript levels was investigated. When human airway epithelial cells (9HTEo-) were treated continuously with 10 nM fluticasone propionate, SLPI transcript levels increased within 12 h, with maximal transcript accumulation occurring at 24-48 h. Several corticosteroids (0.1-1,000 nM) were compared, and the following potency in increasing SLPI transcript levels was observed: fluticasone > triamcinolone > or = dexamethasone > methylprednisolone > hydrocortisone. Fluticasone, the most potent corticosteroid, increased SLPI transcript levels at doses as low as 0.1 nM, whereas hydrocortisone, the least potent corticosteroid, was effective at 100 nM. Fluticasone-induced increases in SLPI transcript levels were inhibited by cycloheximide, suggesting protein synthesis may be required for this response. Because proteases are likely to be present when corticosteroids are administered therapeutically, we examined the interaction between elastase and fluticasone and found they act synergistically to increase SLPI transcript levels. Our findings suggest that corticosteroids may exert their antiinflammatory effects in part by increasing airway epithelial cell SLPI production.