Regulators of A20 (TNFAIP3) - new drug-able targets in inflammation

George Momtazi, Bart N Lambrecht, Jose R Naranjo, Bettina Schock

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)
155 Downloads (Pure)

Abstract

Persistent activation of the transcription factor Nuclear Factor-kappaB (NF-κB) is central to the pathogenesis of many inflammatory disorders, including those of the lung such as cystic fibrosis (CF), asthma, and chronic obstructive pulmonary disease (COPD). Despite recent advances in treatment, management of the inflammatory component of these diseases still remains sub-optimal. A20 is an endogenous negative regulator of NF-κB signalling, which has been widely described in several autoimmune and inflammatory disorders and more recently in terms of chronic lung disorders. However, the underlying mechanism for the apparent lack of A20 in CF, COPD and asthma has not been investigated. Transcriptional regulation of A20 is complex and requires co-ordination of different transcription factors.
In this review we examine the existing body of research evidence on the regulation of A20, concentrating on pulmonary inflammation. Special focus is given to the repressor DREAM and its nuclear and cytosolic action to regulate inflammation. We provide evidence that would suggest the A20-DREAM axis to be an important player in (airway) inflammatory responses and point to DREAM as a potential future therapeutic target for the modification of phenotypic changes in airway inflammatory disorders. A schematic summary describing the role of DREAM in inflammation with a focus on chronic lung diseases as well as the possible consequences of altered DREAM expression on immune responses is provided.
Original languageEnglish
Article numberL-00335-2018R1
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
DOIs
Publication statusPublished - 21 Feb 2019

Keywords

  • TNFAIP3
  • A20 protein
  • DREAM/calsenilin/KChIP3
  • NF-kappaB
  • inflammation

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