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Differential role of pannexin-1/ATP/P2X7 axis in IL-1β release by human monocytes

Parzych, Katarzyna; Zetterqvist, Anna V. LU ; Wright, William R.; Kirkby, Nicholas S; Mitchell, Jane A and Paul-Clark, Mark J. (2017) In FASEB Journal 31(6). p.2439-2445
Abstract

IL-1β release is integral to the innateimmunesystem.The release ofmature IL-1βdepends on 2 regulated events: the de novo induction of pro-IL-1β, generally via NF-κB-dependent transduction pathways; and the assembly and activation of the NLRP3 inflammasome. This latter step is reliant on active caspase-1, pannexin-1, and P2X7 receptor 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. We found that pro-IL-1β and mature IL-1β release fromhumanmonocytes is stimulated by the TLR2 agonists Pam3CSK4 or FSL-1, as well as the TLR4agonist LPSin the absence of additionalATP.TLR2agonists... (More)

IL-1β release is integral to the innateimmunesystem.The release ofmature IL-1βdepends on 2 regulated events: the de novo induction of pro-IL-1β, generally via NF-κB-dependent transduction pathways; and the assembly and activation of the NLRP3 inflammasome. This latter step is reliant on active caspase-1, pannexin-1, and P2X7 receptor 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. We found that pro-IL-1β and mature IL-1β release fromhumanmonocytes is stimulated by the TLR2 agonists Pam3CSK4 or FSL-1, as well as the TLR4agonist LPSin the absence of additionalATP.TLR2agonists requiredpannexin-1 and P2X7 receptor activation to stimulate IL-1β release. In contrast, IL-1β release stimulated by the TLR4 agonist LPS is independent of both pannexin-1 and P2X7 activation. In the absenceof exogenousATP,P2X7 activationrequires endogenousATPrelease, 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 humanmonocytes, both TLR2 and TLR4 signaling induce pro-IL-1β expression, but themechanismbywhich they activate caspase-1diverges at the level of thepannexin-1/ATP/P2X7 axis.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Inflammasome, Innate immunity, Potassium channels, Toll-like receptors
in
FASEB Journal
volume
31
issue
6
pages
7 pages
publisher
The Federation of American Societies for Experimental Biology
external identifiers
  • scopus:85020299103
  • wos:000401553400019
ISSN
0892-6638
DOI
10.1096/fj.201600256
language
English
LU publication?
yes
id
85244dc7-8d30-4c46-988c-e4c976208cfc
date added to LUP
2017-06-27 13:16:53
date last changed
2018-05-06 04:34:36
@article{85244dc7-8d30-4c46-988c-e4c976208cfc,
  abstract     = {<p>IL-1β release is integral to the innateimmunesystem.The release ofmature IL-1βdepends on 2 regulated events: the de novo induction of pro-IL-1β, generally via NF-κB-dependent transduction pathways; and the assembly and activation of the NLRP3 inflammasome. This latter step is reliant on active caspase-1, pannexin-1, and P2X<sub>7</sub> receptor 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. We found that pro-IL-1β and mature IL-1β release fromhumanmonocytes is stimulated by the TLR2 agonists Pam<sub>3</sub>CSK4 or FSL-1, as well as the TLR4agonist LPSin the absence of additionalATP.TLR2agonists requiredpannexin-1 and P2X<sub>7</sub> receptor activation to stimulate IL-1β release. In contrast, IL-1β release stimulated by the TLR4 agonist LPS is independent of both pannexin-1 and P2X<sub>7</sub> activation. In the absenceof exogenousATP,P2X<sub>7</sub> activationrequires endogenousATPrelease, 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 humanmonocytes, both TLR2 and TLR4 signaling induce pro-IL-1β expression, but themechanismbywhich they activate caspase-1diverges at the level of thepannexin-1/ATP/P2X<sub>7</sub> axis.</p>},
  author       = {Parzych, Katarzyna and Zetterqvist, Anna V. and Wright, William R. and Kirkby, Nicholas S and Mitchell, Jane A and Paul-Clark, Mark J.},
  issn         = {0892-6638},
  keyword      = {Inflammasome,Innate immunity,Potassium channels,Toll-like receptors},
  language     = {eng},
  month        = {06},
  number       = {6},
  pages        = {2439--2445},
  publisher    = {The Federation of American Societies for Experimental Biology},
  series       = {FASEB Journal},
  title        = {Differential role of 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},
}