Type

Journal Article

Authors

Noel G McElvaney
Shane J O'Neill
Richard O'Kennedy
Peter Greally
Stephen G J Smith
David A Bergin
Barry Byrne
Michael Williamson
Emer P Reeves

Subjects

Biochemistry

Topics
binding competitive physiology humans metabolism bronchoalveolar lavage fluid child cystic fibrosis adolescent inflammation mediators protein stability child preschool cell line transformed protein binding down regulation jurkat cells chemistry immunology up regulation interleukin 18 glycosaminoglycans interleukin 8 biosynthesis pathology

IL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis. (2009)

Abstract Dysregulation of airway inflammation contributes to lung disease in cystic fibrosis (CF). Inflammation is mediated by inflammatory cytokines, including IL-8, which illustrates an increase in biological half-life and proinflammatory activity when bound to glycosaminoglycans (GAGs). The aim of this project was to compare IL-8 and IL-18 for their relative stability, activity, and interaction with GAGs, including chondroitin sulfate, hyaluronic acid, and heparan sulfate, present in high quantities in the lungs of patients with CF. Bronchoalveolar lavage fluid was collected from patients with CF (n = 28), non-CF controls (n = 14), and patients with chronic obstructive pulmonary disease (n = 12). Increased levels of IL-8 and reduced concentrations of IL-18 were detected in bronchial samples obtained from CF individuals. The low level of IL-18 was not a defect in IL-18 production, as the pro- and mature forms of the molecule were expressed and produced by CF epithelial cells and monocytes. There was, however, a marked competition between IL-8 and IL-18 for binding to GAGs. A pronounced loss of IL-18 binding capacity occurred in the presence of IL-8, which displaced IL-18 from these anionic-matrices, rendering the cytokine susceptible to proteolytic degradation by neutrophil elastase. As a biological consequence of IL-18 degradation, reduced levels of IL-2 were secreted by Jurkat T lymphocytes. In conclusion, a novel mechanism has been identified highlighting the potential of IL-8 to determine the fate of other inflammatory molecules, such as IL-18, within the inflammatory milieu of the CF lung.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Shane J O'Neill, Richard O'Kennedy, Peter Greally, Stephen G J Smith, David A Bergin, Barry Byrne, Michael Williamson, Emer P Reeves

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 190
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 83
 
3
R O'Kennedy
Dublin City University
Total Publications: 197
 
4
Peter Greally
IT Tallaght
Total Publications: 25
 
5
Stephen G J Smith
Trinity College Dublin
Total Publications: 24
 
6
David A Bergin
Royal College of Surgeons in Ireland
Total Publications: 27
 
7
Barry Byrne
Dublin City University
Total Publications: 15
 
8
Emer P Reeves
Royal College of Surgeons in Ireland
Total Publications: 58