Imperial College London
Alternate

ProfessorJaneMitchell

Faculty of Medicine, National Heart & Lung Institute

Professor of Pharmacology in Critical Care Medicine
 
 
 
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Contact

 

+44 (0)20 7351 8137j.a.mitchell

 
 
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Assistant

 

Ms Lisa Quinn +44 (0)20 7594 1345

 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Parzych:2017:10.1096/fj.201600256,
author = {Parzych, K and Zetterqvist, A and Wright, WR and Kirkby, NS and Mitchell, JA and Paul-Clark, M},
doi = {10.1096/fj.201600256},
journal = {The FASEB Journal},
pages = {2439--2445},
title = {Differential role of the pannexin-1/ATP/P2X7 axis in IL-1β release by human monocytes},
url = {http://dx.doi.org/10.1096/fj.201600256},
volume = {31},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - IL-1βrelease is integral to the innateimmune system. The release of mature IL-1β depends on two regulated events; (i) the denovoinduction of pro-IL-1β, generally via NFκB-dependenttransduction pathwaysand (ii) the assembly  and activation  of the NLRP3  inflammasome. This  latter  step  is  reliant  on  active  capase-1, pannexin-1  and  P2X7receptor activation. Pathogen  associated  molecular  patterns  in Gram-positive  and Gram-negative   bacteria activate   IL-1β   release   from   immune   cells   via   TLR2   and   TLR4   receptors respectively. Here,we show that pro-IL-1β and mature IL-1β release from human monocytes is stimulated by the TLR2 agonists,Pam3CSK4 or FSL-1,and the TLR4 agonist,LPS, in the absence of additional ATP. TLR2 agonists required pannexin-1 and P2X7receptor activationto stimulate IL-1βrelease. By contrast, IL-1β release stimulated by the TLR4 agonist,LPS,is independent of both pannexin-1 and P2X7activation. In the  absence  of  exogenous  ATP,P2X7activation  requires endogenous ATP  release,  which  occurs  in  some cells  via  pannexin-1.  In  line  with  this,we  found  that  LPS-stimulated  human  monocytes  released  relatively low levels of ATP,whereas cells stimulated with TLR2 agonists released high levels of ATP. These findings suggest  that,in  human  monocytes,  TLR2  and  TLR4  signalling  bothinduce  pro-IL-1β  expression,but the mechanism by which they activate caspase-1 diverges at the level of the pannexin-1/ATP/P2X7axis.
AU  - Parzych,K
AU  - Zetterqvist,A
AU  - Wright,WR
AU  - Kirkby,NS
AU  - Mitchell,JA
AU  - Paul-Clark,M
DO  - 10.1096/fj.201600256
EP  - 2445
PY  - 2017///
SN  - 0892-6638
SP  - 2439
TI  - Differential role of the pannexin-1/ATP/P2X7 axis in IL-1β release by human monocytes
T2  - The FASEB Journal
UR  - http://dx.doi.org/10.1096/fj.201600256
UR  - http://hdl.handle.net/10044/1/44393
VL  - 31
ER  -
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