Type

Journal Article

Authors

Noel G McElvaney
Shane J O'Neill
Siobhan Griffin
James Devaney
Clifford C Taggart
Stephen G J Smith
Tomás P Carroll
Catherine M Greene

Subjects

Biochemistry

Topics
lipoproteins up regulation antagonists inhibitors membrane glycoproteins interleukin 8 biosynthesis pathology physiology adaptor proteins signal transducing pharmacology cpg oligonucleotide tirap protein human tlr9 protein human interleukin 6 inflammation mediators u937 cells nf kappa b microbiology toll like receptors toll like receptor 4 agonists lipopeptides cell line oligopeptides receptors cell surface myeloid differentiation factor 88 receptors interleukin 1 tlr2 protein human toll like receptor 2 bacterial proteins metabolism bronchoalveolar lavage fluid myd88 protein human toll like receptor 9 oligodeoxyribonucleotides humans macrophage stimulatory lipopeptide 2 cystic fibrosis intercellular adhesion molecule 1 receptors immunologic respiratory mucosa lipopolysaccharides cpg islands genetics immunology pseudomonas infections antigens differentiation tlr4 protein human

TLR-induced inflammation in cystic fibrosis and non-cystic fibrosis airway epithelial cells. (2005)

Abstract Cystic fibrosis (CF) is a genetic disease characterized by severe neutrophil-dominated airway inflammation. An important cause of inflammation in CF is Pseudomonas aeruginosa infection. We have evaluated the importance of a number of P. aeruginosa components, namely lipopeptides, LPS, and unmethylated CpG DNA, as proinflammatory stimuli in CF by characterizing the expression and functional activity of their cognate receptors, TLR2/6 or TLR2/1, TLR4, and TLR9, respectively, in a human tracheal epithelial line, CFTE29o(-), which is homozygous for the DeltaF508 CF transmembrane conductance regulator mutation. We also characterized TLR expression and function in a non-CF airway epithelial cell line 16HBE14o(-). Using RT-PCR, we demonstrated TLR mRNA expression. TLR cell surface expression was assessed by fluorescence microscopy. Lipopeptides, LPS, and unmethylated CpG DNA induced IL-8 and IL-6 protein production in a time- and dose-dependent manner. The CF and non-CF cell lines were largely similar in their TLR expression and relative TLR responses. ICAM-1 expression was also up-regulated in CFTE29o(-) cells following stimulation with each agonist. CF bronchoalveolar lavage fluid, which contains LPS, bacterial DNA, and neutrophil elastase (a neutrophil-derived protease that can activate TLR4), up-regulated an NF-kappaB-linked reporter gene and increased IL-8 protein production in CFTE29o(-) cells. This effect was abrogated by expression of dominant-negative versions of MyD88 or Mal, key signal transducers for TLRs, thereby implicating them as potential anti-inflammatory agents for CF.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Noel G McElvaney, Shane J O'Neill, Siobhan Griffin, James Devaney, Clifford C Taggart, Stephen G J Smith, Tomás P Carroll, Catherine M Greene

Experts in our system

1
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
2
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
3
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
4
Stephen Smith
Trinity College Dublin
Total Publications: 27
 
5
Tomás P Carroll
Royal College of Surgeons in Ireland
Total Publications: 26
 
6
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150