Type

Journal Article

Authors

Shane O'Neill
Noel McElvaney
Clifford C Taggart
Catherine Greene
Ruth MacRedmond

Subjects

Pharmacology

Topics
lung beta defensins tlr4 protein human drug effects toll like receptor 4 epithelial cells metabolism humans respiratory mucosa lipopolysaccharides pharmacology defb4a protein human

Respiratory epithelial cells require Toll-like receptor 4 for induction of human beta-defensin 2 by lipopolysaccharide. (2005)

Abstract The respiratory epithelium is a major portal of entry for pathogens and employs innate defense mechanisms to prevent colonization and infection. Induced expression of human beta-defensin 2 (HBD2) represents a direct response by the epithelium to potential infection. Here we provide evidence for the critical role of Toll-like receptor 4 (TLR4) in lipopolysaccharide (LPS)-induced HBD2 expression by human A549 epithelial cells. Using RTPCR, fluorescence microscopy, ELISA and luciferase reporter gene assays we quantified interleukin-8, TLR4 and HBD2 expression in unstimulated or agonist-treated A549 and/or HEK293 cells. We also assessed the effect of over expressing wild type and/or mutant TLR4, MyD88 and/or Mal transgenes on LPS-induced HBD2 expression in these cells. We demonstrate that A549 cells express TLR4 on their surface and respond directly to Pseudomonas LPS with increased HBD2 gene and protein expression. These effects are blocked by a TLR4 neutralizing antibody or functionally inactive TLR4, MyD88 and/or Mal transgenes. We further implicate TLR4 in LPS-induced HBD2 production by demonstrating HBD2 expression in LPS non-responsive HEK293 cells transfected with a TLR4 expression plasmid. This data defines an additional role for TLR4 in the host defense in the lung.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Shane O'Neill, Noel McElvaney, Clifford C Taggart, Catherine Greene, Ruth 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
Clifford C Taggart
Royal College of Surgeons in Ireland
Total Publications: 54
 
4
Catherine M Greene
Royal College of Surgeons in Ireland
Total Publications: 150