Type

Other / n/a

Authors

Noel G McElvaney
Shane J O'neill
Teck Boon Low
Emer Kelly
Catherine M Greene
Aileen Gibbons
Sinead Weldon
Sally-Ann Cryan
Clifford C Taggart

Subjects

Biochemistry

Topics
cell line lipopolysaccharides cell nucleus secretory cytokines protein transport dna binding proteins enzyme linked immunosorbent assay binding competitive monocytes proteinase inhibitory proteins oligonucleotides medicine and health sciences blotting microscopy proteinase inhibitory proteins secretory blotting western microscopy confocal animals electrophoretic mobility shift assay confocal nf kappa b competitive western rats secretory leukocyte peptidase inhibitor transcription factor rela chromatin immunoprecipitation

Secretory leucoprotease inhibitor binds to NF-kappaB binding sites in monocytes and inhibits p65 binding. (2005)

Abstract Secretory leucoprotease inhibitor (SLPI) is a nonglycosylated protein produced by epithelial cells. In addition to its antiprotease activity, SLPI has been shown to exhibit antiinflammatory properties, including down-regulation of tumor necrosis factor alpha expression by lipopolysaccharide (LPS) in macrophages and inhibition of nuclear factor (NF)-kappaB activation in a rat model of acute lung injury. We have previously shown that SLPI can inhibit LPS-induced NF-kappaB activation in monocytic cells by inhibiting degradation of IkappaBalpha without affecting the LPS-induced phosphorylation and ubiquitination of IkappaBalpha. Here, we present evidence to show that upon incubation with peripheral blood monocytes (PBMs) and the U937 monocytic cell line, SLPI enters the cells, becoming rapidly localized to the cytoplasm and nucleus, and affects NF-kappaB activation by binding directly to NF-kappaB binding sites in a site-specific manner. SLPI can also prevent p65 interaction with the NF-kappaB consensus region at concentrations commensurate with the physiological nuclear levels of SLPI and p65. We also demonstrate the presence of SLPI in nuclear fractions of PBMs and alveolar macrophages from individuals with cystic fibrosis and community-acquired pneumonia. Therefore, SLPI inhibition of NF-kappaB activation is mediated, in part, by competitive binding to the NF-kappaB consensus-binding site.
Collections Ireland -> Royal College of Surgeons in Ireland -> Medicine Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Medicine

Full list of authors on original publication

Noel G McElvaney, Shane J O'neill, Teck Boon Low, Emer Kelly, Catherine M Greene, Aileen Gibbons, Sinead Weldon, Sally-Ann Cryan, Clifford C Taggart

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
4
Sinéad Weldon
Royal College of Surgeons in Ireland
Total Publications: 9
 
5
Sally-Ann Cryan
Royal College of Surgeons in Ireland
Total Publications: 70
 
6
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54