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

First Author  Bickford JS Year  2013
Journal  J Cyst Fibros Volume  12
Issue  3 Pages  258-65
PubMed ID  22985691 Mgi Jnum  J:323178
Mgi Id  MGI:6877471 Doi  10.1016/j.jcf.2012.08.014
Citation  Bickford JS, et al. (2013) Effect of allergy and inflammation on eicosanoid gene expression in CFTR deficiency. J Cyst Fibros 12(3):258-65
abstractText  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.
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