Expression of the NF-κB inhibitor A20 is altered in the Cystic Fibrosis epithelium

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

Research output: Contribution to journalArticle

11 Citations (Scopus)
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Abstract

Research Question: A20 is an LPS-inducible, cytoplasmic zinc finger protein, that inhibits TLR-activated NF-?B signalling by deubiquitinating TRAF6. A20 action is facilitated by complex formation with RNF11, Itch and TAX1BP1. This study investigates if the expression of A20 is altered in the chronically inflamed Cystic Fibrosis (CF) airway epithelium.

Methods: 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-?B subunits was analysed. Formation of the A20 ubiquitin editing complex was also investigated.

Results: 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-.

Conclusion: he 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-?B-driven inflammation.
Original languageEnglish
Article numbererj00324-2012
Pages (from-to)1315-1323
Number of pages9
JournalEuropean Respiratory Journal
Volume41
Issue number6
Early online date27 Sep 2012
DOIs
Publication statusPublished - 27 Sep 2012

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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