Centre for Infection and Immunity, Queen's University of Belfast, Belfast BT97AE, UK.
J Cyst Fibros. 2013 Jul;12(4):411-5. doi: 10.1016/j.jcf.2012.10.009. Epub 2012 Nov 17.
A20 and TAX1BP1 interact to negatively regulate NF-κB-driven inflammation. A20 expression is altered in F508del/F508del patients. Here we explore the effect of CFTR and CFTR genotype on A20 and TAX1BP1 expression. The relationship with lung function is also assessed.
Primary nasal epithelial cells (NECs) from CF patients (F508del/F508del, n=7, R117H/F508del, n=6) and controls (age-matched, n=8), and 16HBE14o- cells were investigated. A20 and TAX1BP1 gene expression was determined by qPCR.
Silencing of CFTR reduced basal A20 expression. Following LPS stimulation A20 and TAX1BP1 expression was induced in control NECs and reduced in CF NECs, broadly reflecting the CF genotype: F508del/F508del had lower expression than R117H/F508del. A20, but not TAX1BP1 expression, was proportional to FEV(1) in all CF patients (r=0.968, p<0.001).
A20 expression is reduced in CF and is proportional to FEV1. Pending confirmation in a larger study, A20 may prove a novel predictor of CF inflammation/disease severity.
A20 和 TAX1BP1 相互作用，负向调节 NF-κB 驱动的炎症。F508del/F508del 患者的 A20 表达发生改变。在此，我们探讨 CFTR 及其基因型对 A20 和 TAX1BP1 表达的影响。并评估其与肺功能的关系。
我们研究了 CF 患者（F508del/F508del，n=7，R117H/F508del，n=6）和对照组（年龄匹配，n=8）的原代鼻上皮细胞（NEC）和 16HBE14o-细胞。通过 qPCR 检测 A20 和 TAX1BP1 的基因表达。
沉默 CFTR 可降低基础 A20 表达。在 LPS 刺激后，对照组 NEC 中 A20 和 TAX1BP1 的表达均被诱导，而 CF NEC 中的表达则降低，这大致反映了 CF 基因型：F508del/F508del 的表达低于 R117H/F508del。在所有 CF 患者中，A20（而非 TAX1BP1）的表达与 FEV1 呈比例关系（r=0.968，p<0.001）。
CF 中 A20 的表达降低，与 FEV1 呈比例关系。在更大规模的研究中得到证实后，A20 可能成为 CF 炎症/疾病严重程度的一个新的预测因子。
