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

Hdl Handle:
http://hdl.handle.net/10147/127096
Title:
IL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis.
Authors:
Reeves, Emer P; Williamson, 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.ie
Citation:
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)
Issue Date:
1-Feb-2010
URI:
http://hdl.handle.net/10147/127096
DOI:
10.4049/jimmunol.0902605
PubMed ID:
20026745
Additional Links:
http://www.jimmunol.org/content/184/3/1642.full.pdf+html
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.
Item Type:
Article
Language:
en
MeSH:
Adolescent; Binding, 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
ISSN:
1550-6606

Full metadata record

DC FieldValue Language
dc.contributor.authorReeves, Emer Pen
dc.contributor.authorWilliamson, Michaelen
dc.contributor.authorByrne, Barryen
dc.contributor.authorBergin, David Aen
dc.contributor.authorSmith, Stephen G Jen
dc.contributor.authorGreally, Peteren
dc.contributor.authorO'Kennedy, Richarden
dc.contributor.authorO'Neill, Shane Jen
dc.contributor.authorMcElvaney, Noel Gen
dc.date.accessioned2011-04-05T11:25:03Z-
dc.date.available2011-04-05T11:25:03Z-
dc.date.issued2010-02-01-
dc.identifier.citationIL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis. 2010, 184 (3):1642-52 J. Immunol.en
dc.identifier.issn1550-6606-
dc.identifier.pmid20026745-
dc.identifier.doi10.4049/jimmunol.0902605-
dc.identifier.urihttp://hdl.handle.net/10147/127096-
dc.description.abstractDysregulation 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.-
dc.language.isoenen
dc.relation.urlhttp://www.jimmunol.org/content/184/3/1642.full.pdf+htmlen
dc.subject.meshAdolescent-
dc.subject.meshBinding, Competitive-
dc.subject.meshBronchoalveolar Lavage Fluid-
dc.subject.meshCell Line, Transformed-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshCystic Fibrosis-
dc.subject.meshDown-Regulation-
dc.subject.meshGlycosaminoglycans-
dc.subject.meshHumans-
dc.subject.meshInflammation Mediators-
dc.subject.meshInterleukin-18-
dc.subject.meshInterleukin-8-
dc.subject.meshJurkat Cells-
dc.subject.meshProtein Binding-
dc.subject.meshProtein Stability-
dc.subject.meshUp-Regulation-
dc.titleIL-8 dictates glycosaminoglycan binding and stability of IL-18 in cystic fibrosis.en
dc.typeArticleen
dc.contributor.departmentRespiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland, Education and Research Centre, Beaumont Hospital, Dublin, Ireland. emerreeves@rcsi.ieen
dc.identifier.journalJournal of immunology (Baltimore, Md. : 1950)en
dc.description.provinceLeinster-

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