EXPRESSION OF THE INFLAMMATORY REGULATOR A20 CORRELATES WITH LUNG FUNCTION IN PATIENTS WITH CYSTIC FIBROSIS

Abstract: Background: A20 and TAX1BP1 interact to negatively regulate NF-<br/>-driven inflammation. A20 expression is altered in F508del/F508del<br/>patients. Here we explore the effect of CFTR and CFTR genotype on A20 and<br/>TAX1BP1expression. The relationship with lung function is also assessed.<br/>Methods: Primary Nasal Epithelial cells (NECs) from CF patients<br/>(F508del/F508del, n=8, R117H/F508del, n=6) and Controls (age-matched,<br/>n=8), and 16HBE14o- cells were investigated. A20 and TAX1BP1 gene<br/>expression was determined by qPCR.<br/>Results: Silencing of CFTR reduced basal A20 expression. Following LPS<br/>stimulation A20 and TAX1BP1 expression was induced in control NECs and<br/>reduced in CF NECs, broadly reflecting the CF genotype: F508del/F508del<br/>had lower expression than R117H/F508del. A20, but not TAX1BP1 expression,<br/>was proportional to FEV1 in all CF patients (r=0.968, p<0.001).<br/>Conclusions: A20 expression is reduced in CF and is proportional to FEV1.<br/>Pending confirmation in a larger study, A20 may prove a novel predictor<br/>of CF inflammation/disease severity.