AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 4 601-L606, Copyright © 1995 by American Physiological Society
Corticosteroids increase secretory leukocyte protease inhibitor transcript levels in airway epithelial cells
J. M. Abbinante-Nissen, L. G. Simpson and G. D. Leikauf
Department of Environmental Health, University of Cincinnati Medical Center, Ohio 45267-0056, USA.
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.
