Toll-like receptors in normal and cystic fibrosis airway epithelial cells

Am J Respir Cell Mol Biol. 2004 Jun;30(6):777-83. doi: 10.1165/rcmb.2003-0329OC. Epub 2003 Dec 4.


Toll-like receptors (TLRs) mediate cellular responses to diverse microbial ligands. The distribution and function of TLRs in airway cells were studied to identify which are available to signal the presence of inhaled pathogens and to establish if differences in TLR expression are associated with the increased proinflammatory responses seen in cystic fibrosis (CF). Isogenic, polarized CF and control bronchial epithelial cell lines, human airway cells in primary culture, and cftr null and wild-type mice were compared. TLRs 1-10, MD2, and MyD88 were expressed in CF and normal cells. Only TLR2 transcription was modestly increased in CF as compared with normal epithelial cells following bacterial stimulation. TLR2 was predominantly at the apical surface of airway cells and was mobilized to cell surface in response to bacteria. TLR4 was present in a more basolateral distribution in airway cells, but appeared to have a limited role in epithelial responses. Lipopolysaccharide failed to activate nuclear factor-kappaB in these cells, and TLR2 dominant negative but not TLR4 dominant negative mutants inhibited activation by both Gram-negative and Gram-positive bacteria. Increased availability of TLR2 at the apical surfaces of CF epithelial cells is consistent with the increased proinflammatory responses seen in CF airways and suggests a selective participation of TLRs in the airway mucosa.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Epithelial Cells / cytology
  • Epithelial Cells / immunology
  • Epithelial Cells / metabolism*
  • G(M1) Ganglioside / metabolism
  • Humans
  • Lipopolysaccharide Receptors / metabolism
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • Mice, Knockout
  • NF-kappa B / metabolism
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism*
  • Respiratory Mucosa / cytology*
  • Respiratory Mucosa / metabolism
  • Signal Transduction / physiology
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors


  • CFTR protein, human
  • Lipopolysaccharide Receptors
  • Membrane Glycoproteins
  • NF-kappa B
  • Receptors, Cell Surface
  • TLR2 protein, human
  • TLR4 protein, human
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • G(M1) Ganglioside
  • asialo GM1 ganglioside