Type

Journal Article

Authors

Shane O'Neill
Noel G McElvaney
Catherine M Greene
Clifford C Taggart

Subjects

Biochemistry

Topics
antagonists inhibitors dna binding proteins slpi protein human secretory leukocyte peptidase inhibitor proteasome endopeptidase complex interleukin 1 receptor associated kinases protein kinases phosphorylation lipopolysaccharides pharmacology metabolism u937 cells slpi protein rat i kappa b proteins humans nf kappab inhibitor alpha multienzyme complexes cysteine endopeptidases i kappa b beta protein proteins ubiquitin proteinase inhibitory proteins secretory

Secretory leucoprotease inhibitor prevents lipopolysaccharide-induced IkappaBalpha degradation without affecting phosphorylation or ubiquitination. (2002)

Abstract Secretory leucoprotease inhibitor (SLPI) is a non-glycosylated protein produced by epithelial cells, macrophages, and neutrophils and was initially identified as a serine protease inhibitor of the neutrophil proteases elastase and cathepsin G. In addition to its antiprotease activity, SLPI has been shown to exhibit anti-inflammatory properties including down-regulation of tumor necrosis factor-alpha expression by lipopolysaccharide (LPS) in monocytes, inhibition of NF-kappaB activation by IgG immune complexes in a rat model of acute lung injury, and prevention of human immunodeficiency virus infectivity in monocytic cells via as yet unidentified mechanisms. In this report we have shown that SLPI prevents LPS-induced NF-kappaB activation by inhibiting degradation of IkappaBalpha without affecting the LPS-induced phosphorylation and ubiquitination of IkappaBalpha. We have also demonstrated that SLPI prevents LPS-induced interleukin-1 receptor-associated kinase and IkappaBbeta degradation. In addition, we have demonstrated that oxidized SLPI, a variant of SLPI that has diminished antiprotease activity, cannot prevent LPS-induced NF-kappaB activation or Inhibitor kappaB alpha/beta degradation indicating that the anti-inflammatory effect of SLPI on the LPS-signaling pathway is dependent on its antiprotease activity. These results suggest that SLPI may be inhibiting proteasomal degradation of NF-kappaB regulatory proteins, an effect that is dependent on the antiprotease activity of SLPI.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Shane O'Neill, Noel G McElvaney, Catherine M Greene, Clifford C Taggart

Experts in our system

1
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
2
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
3
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
4
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54