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

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• 作者：Justin S. Bickford^a ; ¹ ; Christian Mueller^c ; ¹ ; Kimberly J. Newsom^a ; Sarah J. Barilovits^a ; ^b ; Dawn E. Beachy^a ; John D. Herlihy^a ; Benjamin Keeler^a ; Terence R. Flotte^c ; Harry S. Nick^a ; ^{hnick@ufl.edu}
• 关键词：LTs ; leukotrienes ; LTB4 ; leukotriene B4 ; cysLTs ; cysteinyl leukotrienes ; PLA2 ; phospholipase A2 ; sPLA2 ; secretory PLA2 ; cPLA2 ; group IV PLA2 ; HPETEs ; hydroperoxyeicosatetraenoic acids ; HETEs ; hydroxyeicosatetraenoic acids ; CF ; cystic fibrosis ; Af ; Aspergi
• 刊名：Journal of Cystic Fibrosis
• 出版年：2013
• 出版时间：May, 2013
• 年：2013
• 卷：12
• 期：3
• 页码：258-265
• 全文大小：471 K

文摘

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.