Geraghty, Patrick Greene, Catherine M. O'Mahony, Michael O'Neill, Shane J. Taggart, Clifford C. McElvaney, Noel G. Secretory leucocyte protease inhibitor inhibits interferon-gamma-induced cathepsin S expression. 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. Bronchoalveolar Lavage Fluid;Cathepsins;Cations;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;Medicine 2019-11-22
    https://repository.rcsi.com/articles/journal_contribution/Secretory_leucocyte_protease_inhibitor_inhibits_interferon-gamma-induced_cathepsin_S_expression_/10785782