Expression of the nuclear factor-κB inhibitor A20 is altered in the cystic fibrosis epithelium

Catriona Kelly, Mark T. Williams, Kathryn Mitchell, Stuart Elborn, Madeleine Ennis, Bettina Schock

    Research output: Contribution to journalArticlepeer-review


    A20 is a lipopolysaccharide (LPS)-inducible, cytoplasmic zinc finger protein, which
    inhibits Toll-like receptor-activated nuclear factor (NF)-kB signalling by deubiquitinating tumour
    necrosis factor receptor-associated factor (TRAF)-6. The action of A20 is facilitated by complex
    formation with ring finger protein (RNF)-11, Itch and TAX-1 binding protein-1 (TAX1BP1). This
    study investigated whether the expression of A20 is altered in the chronically inflamed cystic
    fibrosis (CF) airway epithelium.
    Nasal epithelial cells from CF patients (F508del homozygous), non-CF controls and immortalised
    epithelial cells (16HBE14o- and CFBE41o-) were stimulated with LPS. Cytoplasmic expression of
    A20 and expression of NF-kB subunits were analysed. Formation of the A20 ubiquitin editing
    complex was also investigated.
    In CFBE41o-, peak LPS-induced A20 expression was delayed compared with 16HBE14o- and
    fell significantly below basal levels 12–24 h after LPS stimulation. This was confirmed in primary
    CF airway cells. Additionally, a significant inverse relationship between A20 and p65 expression
    was observed. Inhibitor studies showed that A20 does not undergo proteasomal degradation in
    CFBE41o-. A20 interacted with TAX1BP1, RNF11 and TRAF6 in 16HBE14o- cells, but these
    interactions were not observed in CFBE41o-.
    The expression of A20 is significantly altered in CF, and important interactions with complex
    members and target proteins are lost, which may contribute to the state of chronic NF-kB-driven
    Original languageEnglish
    Pages (from-to)1315-1323
    Number of pages9
    JournalEuropean Respiratory Journal
    Issue number6
    Early online date31 May 2013
    Publication statusPublished (in print/issue) - 1 Jun 2013


    • A20 protein
    • airway epithelial cells
    • chronic inflammation
    • cystic fibrosis
    • nuclear factor-kB


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