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J. Biol. Chem., Vol. 282, Issue 46, 33389-33395, November 16, 2007

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Secretory Leucocyte Protease Inhibitor Inhibits Interferon--induced Cathepsin S Expression^*

From the Pulmonary Research Division, Beaumont Hospital, Royal College of Surgeons in Ireland, Dublin 9, Ireland

We have demonstrated that bronchoalveolar lavage fluid from chronic obstructive pulmonary disease patients contains higher levels of interferon- compared with controls. Interferon- is a potent inducer of various cathepsins and matrix metalloproteases. Therefore, we postulated that interferon- 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--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--induced cathepsin S production by macrophages. Pretreatment of macrophages with secretory leukocyte protease inhibitor inhibited interferon--induced inhibitor B degradation and activation of nuclear factor B. Secretory leukocyte protease inhibitor may prove to be therapeutically important as a potential inhibitor of protease expression in chronic obstructive pulmonary disease.

Received for publication, August 17, 2007 , and in revised form, September 12, 2007.

^* This work was supported in part by the Health Research Board, The Alpha One Foundation, Science Foundation Ireland, Cystic Fibrosis Research Trust, and Cystic Fibrosis Association of Ireland. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Pulmonary Research Division, RCSI Education, and Research Center, Smurfit Bldg., Beaumont Hospital, Dublin 9, Ireland. Tel.: 00353-18093712; Fax: 00353-1-8093808; E-mail: ctaggart{at}rcsi.ie.

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