Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression.
journal contributionposted on 01.04.2022, 11:21 authored by Patrick Geraghty, Catherine GreeneCatherine Greene, Michael O'Mahony, Shane J. O'Neill, Clifford C. Taggart, Noel G McElvaneyNoel G McElvaney
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.
CommentsAvailable in the Journal of Biological Chemistry at http://www.jbc.org/
Published CitationGeraghty 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.
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