期刊
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
卷 316, 期 3, 页码 L456-L469出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajplung.00335.2018
关键词
A20 protein; calsenilin; DREAM; inflammation; KChIP3; NF-kappa B; TNFAIP3
资金
- Northern Ireland Chest Heart and Stroke [NICHS-2014_15]
- Instituto de Salud Carlos III [Centro Investigacion Biomedica en Red Enfermedades Neurodegenerativas (CIBERNED)]
- COST [BM1406]
- AEI-FEDER, EU [SAF2014-53412-R, SAF2017-89554R]
- MRC [MC_PC_17175] Funding Source: UKRI
Persistent activation of the transcription factor Nuclear factor-kappa B (NF-kappa B) 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 suboptimal. A20 is an endogenous negative regulator of NF-kappa B signaling, 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 coordination 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 downstream regulatory element antagonist modulator (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.
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