Department of Neuroscience, College of Medicine, University of Florida, Gainesville, FL 32610, United States.
J Cyst Fibros. 2013 May;12(3):258-65. doi: 10.1016/j.jcf.2012.08.014. Epub 2012 Sep 15.
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.
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.
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.
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.
变应性支气管肺曲霉病（ABPA）是囊性纤维化（CF）的一种并发症，影响 2-15%的患者。我们假设用烟曲霉（Af）提取物致敏/挑战 CFTR（-/-）小鼠会影响花生四烯酸代谢途径基因表达，从而影响 ABPA 和 CF。
FABP-hCFTR(+/-)-CFTR(-/-) 小鼠用 Af 提取物致敏/挑战，评估肺 mRNA 的 >40 个基因的表达，同时在人类 CF（IB3.1）和 CFTR 校正（S9）支气管上皮细胞系中进行相关数据比较。
在 CFTR（-/-）小鼠中，Pla2g4c、Pla2g2c、Pla2g2d 和 Pla2g5 对 Af 有反应性。有趣的是，只有在 CFTR 缺陷型人类 IB3.1 细胞中，LPS、IL-2、IL-6、IL-13 和 Af 才能诱导 PLA2G2D 的表达。前列腺素基因表达相对稳定，但 Af 可诱导多个 12/15-脂氧合酶基因的表达。许多细胞因子也仅在 IB3.1 细胞中导致 ALOX15 的差异表达。
在曲霉致敏和/或囊性纤维化中 PLA2G4C、PLA2G2D 和 ALOX15 基因的独特调控可能为 ABPA 和 CF 的诊断和治疗提供新的思路。
