IL-17 primes airway epithelial cells lacking functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) to increase NOD1 responses

Biochem Biophys Res Commun. 2010 Jan 1;391(1):505-9. doi: 10.1016/j.bbrc.2009.11.088. Epub 2009 Nov 20.


In Cystic Fibrosis (CF), the absence of functional Cystic Fibrosis Transmembrane conductance Regulator (CFTR) translates into chronic bacterial infection, excessive inflammation, tissue damage, impaired lung function and eventual death. Understanding the mechanisms underlying this vicious circle of inflammation is key to better therapies for CF. In this manuscript, we have found that the presence of IL-17 in the airways of CF patients not only exacerbates inflammation through the recruitment of neutrophils via secretion of CXCL8, but also by priming airway epithelial cells lacking functional CFTR to increase response to the bacterial sensor NOD1. IL-17 stimulation of airway epithelial cells (AECs) lacking functional CFTR increased the expression of NOD1, NOD2, TLR4 and its own receptors IL-17RA and IL-17RC. Moreover, prior stimulation of AECs expressing the CFTRDeltaF508 mutant with IL-17 showed much greater CXCL8 secretion in response to a NOD1 agonist and Pseudomonas aeruginosa diffusible material. Taken together our results show that IL-17 primes AECs expressing CFTRDeltaF508 to increase host defence response to bacteria through the up-regulation of PRRs, and in particular of NOD1, and identifies another mechanism of action through which the CFTRDeltaF508 mutation leads to increase inflammation in response to bacterial ligands. Therefore preventing IL-17 function in CF may prove an important strategy in decreasing lung inflammation due to both direct and indirect effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Cells, Cultured
  • Cystic Fibrosis / complications*
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / immunology
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Epithelial Cells / immunology
  • Epithelial Cells / microbiology
  • Epithelial Cells / pathology
  • Humans
  • Interleukin-17 / metabolism*
  • Interleukin-8 / metabolism
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology
  • Neutrophils / immunology
  • Nod1 Signaling Adaptor Protein / biosynthesis*
  • Pseudomonas Infections / immunology*
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa*
  • Receptors, Interleukin-17 / biosynthesis
  • Respiratory Mucosa / immunology*
  • Respiratory Mucosa / microbiology
  • Respiratory Mucosa / pathology
  • Toll-Like Receptor 4 / biosynthesis


  • CXCL8 protein, human
  • IL17RA protein, human
  • Interleukin-17
  • Interleukin-8
  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • Receptors, Interleukin-17
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Cystic Fibrosis Transmembrane Conductance Regulator