Expression of the inflammatory regulator A20 correlates with lung function in patients with cystic fibrosis

Background: A20 and TAX1BP1 interact to negatively regulate NF-kappa B-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. Methods: 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. Results: 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 FEV1 in all CF patients (r=0.968, p<0.001). Conclusions: 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. (c) 2012 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.