title: Effect of allergy and inflammation on eicosanoid gene expression in CFTR deficiency.
abstract: BACKGROUND
  Allergic bronchopulmonary aspergillosis (ABPA) is a complicating factor in cystic fibrosis (CF), affecting 2-15% of patients. We hypothesized that sensitization/challenge of CFTR(-/-) mice with an Aspergillus fumigatus (Af) extract will affect eicosanoid pathway gene expression, impacting ABPA and CF.
  
  
  METHODS
  FABP-hCFTR(+/-)-CFTR(-/-) mice were sensitized/challenged with an Af extract and gene expression of lung mRNA was evaluated for >40 genes, with correlative data in human CF (IB3.1) and CFTR-corrected (S9) bronchoepithelial cell lines.
  
  
  RESULTS
  Pla2g4c, Pla2g2c, Pla2g2d and Pla2g5 were induced in response to Af in CFTR(-/-) mice. Interestingly, PLA2G2D was induced by LPS, IL-2, IL-6, IL-13, and Af only in CFTR-deficient human IB3.1 cells. Prostanoid gene expression was relatively constant, however, several 12/15-lipoxygenase genes were induced in response to Af. Numerous cytokines also caused differential expression of ALOX15 only in IB3.1 cells.
  
  
  CONCLUSIONS
  The distinct regulation of PLA2G4C, PLA2G2D and ALOX15 genes in Aspergillus sensitization and/or cystic fibrosis could provide new insights into diagnosis and treatment of ABPA and CF.
authors.affiliation: Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, United States.
authors.forename: Justin S
authors.initials: JS
authors.lastname: Bickford
authors.forename: Christian
authors.initials: C
authors.lastname: Mueller
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Newsom
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Barilovits
authors.forename: Dawn E
authors.initials: DE
authors.lastname: Beachy
authors.forename: John D
authors.initials: JD
authors.lastname: Herlihy
authors.forename: Benjamin
authors.initials: B
authors.lastname: Keeler
authors.forename: Terence R
authors.initials: TR
authors.lastname: Flotte
authors.forename: Harry S
authors.initials: HS
authors.lastname: Nick
mesh_terms: D000818:Animals; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000235:genetics*; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000172:deficiency*; D005786:Gene Expression Regulation; D006801:Humans; D006967:Hypersensitivity / Q000235:genetics*; D007249:Inflammation / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator