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Effect of allergy and inflammation on eicosanoid gene expression in CFTR deficiency

Justin S Bickford1, Christian Mueller, Kimberly J Newsom

  • 1Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, United States.

Journal of Cystic Fibrosis : Official Journal of the European Cystic Fibrosis Society
|September 19, 2012
PubMed
Abstract

Insights

This study shows that Aspergillus fumigatus (Af) exposure alters eicosanoid gene expression in cystic fibrosis (CF) models. Specific gene changes in CFTR-deficient cells offer insights into allergic bronchopulmonary aspergillosis (ABPA) and CF.

Area of Science:

  • Biochemistry
  • Immunology
  • Genetics

Background:

  • Allergic bronchopulmonary aspergillosis (ABPA) complicates cystic fibrosis (CF) in 2-15% of patients.
  • Investigates the impact of Aspergillus fumigatus (Af) sensitization on eicosanoid pathway gene expression in CF models.

Purpose of the Study:

  • To explore the relationship between Af sensitization, CFTR deficiency, and eicosanoid pathway gene expression.
  • To identify potential molecular targets for ABPA and CF diagnosis and treatment.

Main Methods:

  • Utilized CFTR(-/-) mice sensitized and challenged with Af extract.
  • Analyzed lung mRNA gene expression for over 40 genes.
  • Correlated findings with human CF (IB3.1) and corrected (S9) bronchoepithelial cell lines.

Main Results:

  • Af induced Pla2g4c, Pla2g2c, Pla2g2d, and Pla2g5 in CFTR(-/-) mice.
  • PLA2G2D was induced by various stimuli including Af, LPS, and cytokines specifically in CFTR-deficient IB3.1 cells.
  • Several 12/15-lipoxygenase genes were induced by Af, with differential ALOX15 expression in IB3.1 cells.

Conclusions:

  • Distinct regulation of PLA2G4C, PLA2G2D, and ALOX15 genes in Af sensitization and CF.
  • These findings may offer novel diagnostic and therapeutic strategies for ABPA and CF.

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