IL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis.
Authors
Reeves, Emer PWilliamson, Michael
Byrne, Barry
Bergin, David A
Smith, Stephen G J
Greally, Peter
O'Kennedy, Richard
O'Neill, Shane J
McElvaney, Noel G
Affiliation
Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. emerreeves@rcsi.ieIssue Date
2010-02-01MeSH
AdolescentBinding, Competitive
Bronchoalveolar Lavage Fluid
Cell Line, Transformed
Child
Child, Preschool
Cystic Fibrosis
Down-Regulation
Glycosaminoglycans
Humans
Inflammation Mediators
Interleukin-18
Interleukin-8
Jurkat Cells
Protein Binding
Protein Stability
Up-Regulation
Metadata
Show full item recordCitation
IL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis. 2010, 184 (3):1642-52 J. Immunol.Journal
Journal of immunology (Baltimore, Md. : 1950)DOI
10.4049/jimmunol.0902605PubMed ID
20026745Additional Links
http://www.jimmunol.org/content/184/3/1642.full.pdf+htmlAbstract
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.Item Type
ArticleLanguage
enISSN
1550-6606ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.0902605
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