O'Reilly, Susan M. and Moynagh, Paul N. (2003) Regulation of Toll-like receptor 4 signalling by A20 zinc finger protein. Biochemical and Biophysical Research Communications, 303 (2). pp. 586-593. ISSN 0006-291X

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Abstract

A20 is a zinc finger protein that renders cells resistant to apoptosis. However, the recent demonstration that A20-deficient mice develop severe inflammation and are hyper-responsive to LPS suggests that A20 may play a key role in regulating the inflammatory response. This study, for the first time, explores the likely mechanism by which A20 can regulate the pro-inflammatory effects of LPS. More specifically it characterises the ability of A20 to modulate TLR-4 signalling since TLR-4 acts as the signalling receptor system for LPS. Full length A20 inhibited the ability of TLR-4 to activate the transcription factors, NF-jB and AP-1, and induce the chemokine IL-8. The inhibitory capacity of A20 on NF-jB was localised to the C-terminal zinc finger domain of A20 whereas full length A20 was required to effect inhibition of AP-1 and IL-8. Furthermore full length and C-terminal A20 showed similar regulatory effects on MEKK-1 activation of NF-jB and AP-1 and induction of IL-8. The findings increase our mechanistic understanding of the anti-inflammatory effects of A20 and suggest that it modulates TLR-4 signalling at or downstream of MEKK-1.

Item Type:	Article
Keywords:	Inflammation; Signal transduction; Transcription factors; Toll-like receptor;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	7208
Identification Number:	https://doi.org/10.1016/S0006-291X(03)00389-9
Depositing User:	Professor Paul Moynagh
Date Deposited:	20 Jul 2016 16:02
Journal or Publication Title:	Biochemical and Biophysical Research Communications
Publisher:	Academic Press
Refereed:	Yes
Funders:	European Biotechnology 5th Framework Programme, Health Research Board (HRB), Enterprise Ireland (EI)
URI:	http://www.sciencedirect.com
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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