Peer Reviewed

1

Document Type

Article

Publication Date

16-11-2007

Keywords

Bronchoalveolar Lavage Fluid, Cathepsins, Cations, Gene Expression Regulation, Gene Expression Regulation, Enzymologic, Humans, Interferon-gamma, Leukocytes, Mononuclear, Macrophages, Matrix Metalloproteinase 12, NF-kappa B, Pulmonary Disease, Chronic Obstructive, Secretory Leukocyte Peptidase Inhibitor, Subcellular Fractions, U937 Cells

Comments

Available in the Journal of Biological Chemistry at http://www.jbc.org/

Abstract

We have demonstrated that bronchoalveolar lavage fluid from chronic obstructive pulmonary disease patients contains higher levels of interferon-gamma compared with controls. Interferon-gamma is a potent inducer of various cathepsins and matrix metalloproteases. Therefore, we postulated that interferon-gamma could induce protease expression by macrophages in acute and chronic lung disease. Chronic obstructive pulmonary disease patients had greater levels of cathepsin S and matrix metalloprotease-12 in their bronchoalveolar lavage fluid. Macrophages incubated with chronic obstructive pulmonary disease bronchoalveolar lavage fluid exhibited increased expression of cathepsin S and matrix metalloprotease-12, which was inhibited by the addition of interferon-gamma-neutralizing immunoglobulin. Human secretory leukocyte protease inhibitor is an 11.7-kDa cationic non-glycosylated antiprotease synthesized and secreted by cells at the site of inflammation. We have demonstrated that secretory leukocyte protease inhibitor can inhibit interferon-gamma-induced cathepsin S production by macrophages. Pretreatment of macrophages with secretory leukocyte protease inhibitor inhibited interferon-gamma-induced inhibitor kappaB beta degradation and activation of nuclear factor kappaB. Secretory leukocyte protease inhibitor may prove to be therapeutically important as a potential inhibitor of protease expression in chronic obstructive pulmonary disease.

Disciplines

Medicine and Health Sciences

Citation

Geraghty P, Greene CM, O'Mahony M, O'Neill SJ, Taggart CC, McElvaney NG. Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression. Journal of Biological Chemistry 2007; 282(46):33389-95.

PubMed ID

17878156

DOI Link

10.1074/jbc.M706884200

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