Bruton's tyrosine kinase regulates TLR7/8-induced TNF transcription via nuclear factor-κB recruitment

Page, Theresa H., Urbaniak, Anna M., Espirito Santo, Ana I., Danks, Lynett, Smallie, Timothy, Williams, Lynn M. and Horwood, Nicole J. ORCID: (2018) Bruton's tyrosine kinase regulates TLR7/8-induced TNF transcription via nuclear factor-κB recruitment. Biochemical and Biophysical Research Communications, 499 (2). pp. 260-266. ISSN 0006-291X

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Tumour necrosis factor (TNF) is produced by primary human macrophages in response to stimulation by exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs) via Toll-like receptor (TLR) signalling. However, uncontrolled TNF production can be deleterious and hence it is tightly controlled at multiple stages. We have previously shown that Bruton's tyrosine kinase (Btk) regulates TLR4-induced TNF production via p38 MAP Kinase by stabilising TNF messenger RNA. Using both gene over-expression and siRNA-mediated knockdown we have examined the role of Btk in TLR7/8 mediated TNF production. Our data shows that Btk acts in the TLR7/8 pathway and mediates Ser-536 phosphorylation of p65 RelA and subsequent nuclear entry in primary human macrophages. These data show an important role for Btk in TLR7/8 mediated TNF production and reveal distinct differences for Btk in TLR4 versus TLR7/8 signalling.

Item Type: Article
Additional Information: Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Uncontrolled Keywords: genetics,agammaglobulinaemia tyrosine kinase,genetics,metabolism,biosynthesis,genetics,humans,metabolism,phosphorylation,genetics,metabolism,metabolism,metabolism,metabolism,metabolism,transcription, genetic,genetics
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 06 Mar 2019 11:30
Last Modified: 19 Oct 2023 02:23
DOI: 10.1016/j.bbrc.2018.03.140


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