Type

Journal Article

Authors

Shane J O'Neill
Noel G McElvaney
Delbert R Dorscheid
Catherine M Greene
Ruth E MacRedmond

Subjects

Pharmacology

Topics
pharmacology rna messenger pulmonary disease chronic obstructive severity of illness index beta defensins tlr4 protein human adrenal cortex hormones drug effects toll like receptor 4 androstadienes analogs derivatives cell line smoking respiratory mucosa salmeterol adult humans fluticasone gene expression regulation drug therapy female therapeutic use lipopolysaccharides genetics metabolism adrenergic beta agonists interleukin 8 albuterol nasal mucosa male dose response relationship drug aged case control studies dexamethasone defb4a protein human adverse effects middle aged smoke drug interactions

Epithelial expression of TLR4 is modulated in COPD and by steroids, salmeterol and cigarette smoke. (2007)

Abstract The toll-like receptors (TLRs) are a key component of host defense in the respiratory epithelium. Cigarette smoking is associated with increased susceptibility to infection, while COPD is characterised by bacterial colonisation and infective exacerbations. We found reduced TLR4 gene expression in the nasal epithelium of smokers compared with non-smoking controls, while TLR2 expression was unchanged. Severe COPD was associated with reduced TLR4 expression compared to less severe disease, with good correlation between nasal and tracheal expression. We went on to examine the effect of potential modulators of TLR4 expression in respiratory epithelium pertinent to airways disease. Using an airway epithelial cell line, we found a dose-dependent downregulation in TLR4 mRNA and protein expression by stimulation with cigarette smoke extracts. Treatment with the corticosteroids fluticasone and dexamethasone resulted in a dose-dependent reduction in TLR4 mRNA and protein. The functional significance of this effect was demonstrated by impaired IL-8 and HBD2 induction in response to LPS. Stimulation with salmeterol (10-6 M) caused upregulation of TLR4 membrane protein presentation with no upregulation of mRNA, suggesting a post-translational effect. The effect of dexamethasone and salmeterol in combination was additive, with downregulation of TLR4 gene expression, and no change in membrane receptor expression. Modulation of TLR4 in respiratory epithelium may have important implications for airway inflammation and infection in response to inhaled pathogens.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Shane J O'Neill, Noel G McElvaney, Delbert R Dorscheid, Catherine M Greene, Ruth E MacRedmond

Experts in our system

1
Shane J O'Neill
Royal College of Surgeons in Ireland
Total Publications: 84
 
2
Noel G McElvaney
Royal College of Surgeons in Ireland
Total Publications: 194
 
3
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150