AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 4 601-L606, Copyright © 1995 by American Physiological Society

ARTICLES

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.

This article has been cited by other articles:

				M. Salter, K. Biggadike, J. L. Matthews, M. R. West, M. V. Haase, S. N. Farrow, I. J. Uings, and D. W. Gray Pharmacological properties of the enhanced-affinity glucocorticoid fluticasone furoate in vitro and in an in vivo model of respiratory inflammatory disease Am J Physiol Lung Cell Mol Physiol, September 1, 2007; 293(3): L660 - L667. [Abstract] [Full Text] [PDF]

				W. Lu, E. P. Lillehoj, and K. C. Kim Effects of dexamethasone on Muc5ac mucin production by primary airway goblet cells Am J Physiol Lung Cell Mol Physiol, January 1, 2005; 288(1): L52 - L60. [Abstract] [Full Text] [PDF]

				P A Beckett and P H Howarth Pharmacotherapy and airway remodelling in asthma? Thorax, February 1, 2003; 58(2): 163 - 174. [Abstract] [Full Text] [PDF]

				W. I. de Boer Cytokines and Therapy in COPD* : A Promising Combination? Chest, May 1, 2002; 121(5_suppl): 209S - 218S. [Abstract] [Full Text] [PDF]

				H. Saitoh, T. Masuda, S. Shimura, T. Fushimi, and K. Shirato Secretion and gene expression of secretory leukocyte protease inhibitor by human airway submucosal glands Am J Physiol Lung Cell Mol Physiol, January 1, 2001; 280(1): L79 - L87. [Abstract] [Full Text] [PDF]

				S Gompertz, D L Bayley, S L Hill, and R A Stockley Relationship between airway inflammation and the frequency of exacerbations in patients with smoking related COPD Thorax, January 1, 2001; 56(1): 36 - 41. [Abstract] [Full Text]

				R. Newton Molecular mechanisms of glucocorticoid action: what is important? Thorax, July 1, 2000; 55(7): 603 - 613. [Full Text]

				S. van Wetering, A. C. van der Linden, M. A. J. A. van Sterkenburg, W. I. de Boer, A. L. A. Kuijpers, J. Schalkwijk, and P. S. Hiemstra Regulation of SLPI and elafin release from bronchial epithelial cells by neutrophil defensins Am J Physiol Lung Cell Mol Physiol, January 1, 2000; 278(1): L51 - L58. [Abstract] [Full Text] [PDF]

				T. Kikuchi, T. Abe, S. Hoshi, N. Matsubara, Y. Tominaga, K. Satoh, and T. Nukiwa Structure of the Murine Secretory Leukoprotease Inhibitor (Slpi) Gene and Chromosomal Localization of the Human and Murine SLPI Genes Am. J. Respir. Cell Mol. Biol., December 1, 1998; 19(6): 875 - 880. [Abstract] [Full Text]

				F. Jin, C. F. Nathan, D. Radzioch, and A. Ding Lipopolysaccharide-Related Stimuli Induce Expression of the Secretory Leukocyte Protease Inhibitor, a Macrophage-Derived Lipopolysaccharide Inhibitor Infect. Immun., June 1, 1998; 66(6): 2447 - 2452. [Abstract] [Full Text] [PDF]

				A. Boutten, P. Venembre, N. Seta, J. Hamelin, M. Aubier, G. Durand, and M. S. Dehoux Oncostatin M Is a Potent Stimulator of alpha 1-Antitrypsin Secretion in Lung Epithelial Cells: Modulation by Transforming Growth Factor-beta and Interferon-gamma Am. J. Respir. Cell Mol. Biol., April 1, 1998; 18(4): 511 - 520. [Abstract] [Full Text]

				T. Kikuchi, T. Abe, K. Satoh, K. Narumi, T. Sakai, S. Abe, S. Shindoh, K. Matsushima, and T. Nukiwa Cis-acting Region Associated with Lung Cell-specific Expression of the Secretory Leukoprotease Inhibitor Gene Am. J. Respir. Cell Mol. Biol., September 1, 1997; 17(3): 361 - 367. [Abstract] [Full Text]