Type

Journal Article

Authors

Noel G McElvaney
Clifford C Taggart
Shane J O'Neill
Abderazzaq Belaaouaj
Michael O'Mahony
Tiphaine Poiriert
Rachel M M Boxio
Catherine M Greene
Mark P Rogan
Patrick Geraghty

Subjects

Biochemistry

Topics
drug effects microbiology cathepsin b genes dominant transfection toll like receptor 4 enzymology lung mice humans metabolism mice knockout irak1 protein mouse immunology macrophages pseudomonas infections genetics interleukin 8 interleukin 1 receptor associated kinases physiology pseudomonas aeruginosa pharmacology animals nf kappa b matrix metalloproteinase 2 leukocyte elastase

Neutrophil elastase up-regulates cathepsin B and matrix metalloprotease-2 expression. (2007)

Abstract Neutrophil elastase (NE) activity is increased in many diseases. Other families of proteases, including cathepsins and matrix metalloproteases (MMPs), are also present at elevated levels in similar disease conditions. We postulated that NE could induce expression of cathepsins and MMPs in human macrophages. NE exposure resulted in macrophages, producing significantly greater amounts of cathepsin B and latent and active MMP-2. Cathepsin B and MMP-2 activities were decreased in Pseudomonas-infected NE knockout mice compared with wild-type littermates. We also demonstrate that NE can activate NF-kappaB in macrophages, and inhibition of NF-kappaB resulted in a reduction of NE-induced cathepsin B and MMP-2. Also, inhibition of TLR-4 or transfection of macrophages with dominant-negative IL-1R-associated kinase-1 resulted in a reduction of NE-induced cathepsin B and MMP-2. This study describes for the first time a novel hierarchy among proteases whereby a serine protease up-regulates expression of MMPs and cathepsins. This has important implications for therapeutic intervention in protease-mediated diseases.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Clifford C Taggart, Shane J O'Neill, Abderazzaq Belaaouaj, Michael O'Mahony, Tiphaine Poiriert, Rachel M M Boxio, Catherine M Greene, Mark P Rogan, Patrick Geraghty

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
3
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150
 
5
Patrick Geraghty
Royal College of Surgeons in Ireland
Total Publications: 13