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.
Geraghty
Patrick
P
Pulmonary Research Division, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
Greene
Catherine M
CM
Pulmonary Research Division, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
O'Mahony
Michael
M
Pulmonary Research Division, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
O'Neill
Shane J
SJ
Pulmonary Research Division, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
Taggart
Clifford C
CC
Pulmonary Research Division, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland. Electronic address: ctaggart@rcsi.ie.
McElvaney
Noel G
NG
Pulmonary Research Division, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
D001992:Bronchoalveolar Lavage Fluid; D002403:Cathepsins / Q000378:metabolism*; D002412:Cations; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000502:physiology*; D013347:Subcellular Fractions / Q000378:metabolism; D020298:U937 Cells
D002412:Cations; D016328:NF-kappa B; D053481:Secretory Leukocyte Peptidase Inhibitor; D007371:Interferon-gamma; D002403:Cathepsins; C028217:cathepsin S; D053508:Matrix Metalloproteinase 12