Linked Life Data

20438838

Source:http://linkedlifedata.com/resource/pubmed/id/20438838

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7-8
pubmed:dateCreated
2010-6-28
pubmed:abstractText
The ability of IL-6 to signal via both membrane bound and soluble receptors is thought to explain the capacity of this cytokine to act in both the initiation and resolution of acute inflammatory responses. In cystic fibrosis (CF), poorly resolved neutrophillic inflammation of the lungs is a primary cause of morbidity and mortality. Expression of IL-6 has been reported to be low in CF lung secretions, despite ongoing inflammation, but the status of soluble IL-6 receptor (sIL-6R) in these patients is unknown. We hypothesised that sIL-6R may be an important potentiator of IL-6 activity in CF associated lung disease. IL-6, sIL-6R and sgp130 (a natural antagonist of responses mediated by the sIL-6R) were analysed by ELISA and Western blot in bronchoalveolar lavage fluid (BALF) from 28 paediatric CF patients and nine non-CF controls. Total cell counts in CF were four fold higher compared to controls (median: 1.4 x 10(6) cells/ml v. 0.35 x 10(6) cells/ml in controls) (p<0.001) and the infiltrate was dominated by neutrophils which were elevated by 89 fold (0.62 x 10(6) cells/ml v. 0.007 x 10(6) cells/ml in controls) (p<0.001). Other markers of inflammation such as IL-8 and MCP-1 were elevated 17.5 and 3.8 fold respectively (IL-8; median: 1122 pg/ml v. 64 pg/ml in controls, p<0.01 and MCP-1; median: 692 pg/ml v. 182 pg/ml in controls, p<0.05). IL-6, although present in 23/32 CF BALF specimens compared to 1/9 controls (p<0.01), was weakly expressed (median: 50 pg/ml). Expression of sIL-6R and sgp130 in CF was no different to control patients. We tested whether weak expression of all three molecules was due to degradation by CF BALF. Degradative activity was observed in association with BALF elastase activity and could be specifically blocked by serine protease inhibitors. Degradation of sIL-6R by purified serine proteases (elastase, cathepsin G and proteinase 3) was also observed leading to a loss of trans-signalling activity. Interestingly, sIL-6R was protected from proteolysis by interaction with IL-6. Our data identify and define a novel protease mediated deficiency of IL-6 signalling in the CF lung.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0006-3002
pubmed:author
pubmed:copyrightInfo
Copyright 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:volume
1802
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
649-58
pubmed:meshHeading
pubmed:articleTitle
Inactivation of IL-6 and soluble IL-6 receptor by neutrophil derived serine proteases in cystic fibrosis.
pubmed:affiliation
Department of Child Health, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK. mcgrealep@cf.ac.uk
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't