Corr4A and VRT325 do not reduce the inflammatory response to P. aeruginosa in human cystic fibrosis airway epithelial cells

Cell Physiol Biochem. 2009;23(1-3):199-204. doi: 10.1159/000204108. Epub 2009 Feb 18.

Abstract

Background: P. aeruginosa chronically colonizes the lung in CF patients and elicits a proinflammatory response. Excessive secretion of IL-6 and IL-8 by CF airway cells in response to P. aeruginosa infection in the CF airway is though to contribute to lung injury. Accordingly, the goal of this study was to test the hypothesis that Corr4a and VRT325, investigational compounds that increase DeltaF508-CFTR mediated Cl(-) secretion in human CF airway cells, reduce the pro-inflammatory response to P. aeruginosa.

Methods: IL-6 and IL-8 secretion by polarized CF human airway epithelial cells (CFBE41o-) were measured by multiplex analysis, and DeltaF508-CFTR Cl- secretion was measured in Ussing chambers. Airway cells were exposed to P. aeruginosa (PAO1 or PA14) and Corr4a or VRT325.

Results: Corr4a and VRT325 increased DeltaF508-CFTR Cl(-) secretion but did not reduce either constitutive IL-6 or IL-8 secretion, or IL-6 and IL-8 secretion stimulated by P. aeruginosa (PA14 or PAO1).

Conclusions: Corr4a and VRT325 do not reduce the inflammatory response to P. aeruginosa in human cystic fibrosis airway epithelial cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Cystic Fibrosis / drug therapy*
  • Cystic Fibrosis / pathology
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / therapeutic use*
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Epithelial Cells / microbiology*
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / immunology*
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use*

Substances

  • 4-cyclohexyloxy-2-(1-(4-(4-methoxy-benzenesulfonyl)piperazin-1-yl)ethyl)quinazoline
  • Interleukin-6
  • Interleukin-8
  • Piperazines
  • Quinazolines
  • cystic fibrosis transmembrane conductance regulator delta F508
  • Cystic Fibrosis Transmembrane Conductance Regulator