title: The Ability of Secretory Leukocyte Protease Inhibitor to Inhibit Apoptosis in Monocytes Is Independent of Its Antiprotease Activity.
abstract: Secretory Leukocyte Protease Inhibitor (SLPI) is a serine protease inhibitor produced by epithelial and myeloid cells with anti-inflammatory properties. Research has shown that SLPI exerts its anti-inflammatory activity by directly binding to NF-κB DNA binding sites and, in so doing, prevents binding and subsequent transcription of proinflammatory gene expression. In the current study, we demonstrate that SLPI can inhibit TNF-α-induced apoptosis in U937 cells and peripheral blood monocytes. Specifically, SLPI inhibits TNF-α-induced caspase-3 activation and DNA degradation associated with apoptosis. We go on to show that this ability of SLPI to inhibit apoptosis is not dependent on its antiprotease activity as antiprotease deficient variants of SLPI can also inhibit TNF-α-induced apoptosis. This reduction in monocyte apoptosis may preserve monocyte function during inflammation resolution and promote infection clearance at mucosal sites.
authors.affiliation: Respiratory Research Division, Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
authors.forename: Niamh
authors.initials: N
authors.lastname: McGarry
authors.affiliation: Respiratory Research Division, Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Greene
authors.affiliation: Respiratory Research Division, Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Dublin 9, Ireland.
authors.forename: Noel G
authors.initials: NG
authors.lastname: McElvaney
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Health Sciences Building, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK.
authors.forename: Sinéad
authors.initials: S
authors.lastname: Weldon
authors.affiliation: Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, Health Sciences Building, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7AE, UK.
authors.forename: Clifford C
authors.initials: CC
authors.lastname: Taggart
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D010084:Oxidation-Reduction; D053491:Proteinase Inhibitory Proteins, Secretory / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D053491:Proteinase Inhibitory Proteins, Secretory; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D053179:Caspase 7