Corr4A and VRT325 do not reduce the inflammatory response to P. aeruginosa in human cystic fibrosis airway epithelial cells.
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.
Talebian
Laleh
L
Department of Physiology, Dartmouth Medical School, Hanover, Germany. Laleh.Talebian@Dartmouth.EDU
Coutermarsh
Bonita
B
Channon
Jacqueline Y
JY
Stanton
Bruce A
BA
D002460:Cell Line; D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000473:pathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000378:metabolism / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000276:immunology*; D011799:Quinazolines / Q000494:pharmacology / Q000627:therapeutic use*
C507255:4-cyclohexyloxy-2-(1-(4-(4-methoxy-benzenesulfonyl)piperazin-1-yl)ethyl)quinazoline; D015850:Interleukin-6; D016209:Interleukin-8; D010879:Piperazines; D011799:Quinazolines; C093349:cystic fibrosis transmembrane conductance regulator delta F508; D019005:Cystic Fibrosis Transmembrane Conductance Regulator