CORTICOSTEROIDS INCREASE SECRETORY LEUKOCYTE PROTEASE INHIBITOR TRANSCRIPT LEVELS IN AIRWAY EPITHELIAL-CELLS

Secretory leukocyte protease inhibitor (SLPI) is the predominant antip rotease of the conducting airways and may play a role in reducing airw ay 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 transcrip t levels increased within 12 h, with maximal transcript accumulation o ccurring at 24-48 h. Several corticosteroids (0.1-1,000 nM) were compa red, and the following potency in increasing SLPI transcript levels wa s observed: fluticasone > triamcinolone greater than or equal to dexam ethasone. methylprednisolone > hydrocortisone. Fluticasone, the most p otent corticosteroid, increased SLPI transcript levels at doses as low as 0.1 nM, whereas hydrocortisone, the least potent corticosteroid, w as effective at 100 nM. Fluticasone-induced increases in SLPI transcri pt levels were inhibited by cycloheximide, suggesting protein synthesi s may be required for this response. Because proteases are likely to b e present when corticosteroids are administered therapeutically, we ex amined 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.