PMID- 35353387
OWN - NLM
STAT- MEDLINE
DCOM- 20220509
LR  - 20220829
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 70
IP  - 7
DP  - 2022 Jul
TI  - The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation.
PG  - 1301-1316
LID - 10.1002/glia.24174 [doi]
AB  - The NLRP3 (NLR family, pyrin domain containing 3) inflammasome is a multi-protein 
      complex responsible for the activation of caspase-1 and the subsequent cleavage 
      and activation of the potent proinflammatory cytokines IL-1beta and IL-18, and 
      pyroptotic cell death. NLRP3 is implicated as a driver of inflammation in a range 
      of disorders including neurodegenerative diseases, type 2 diabetes, and 
      atherosclerosis. A commonly reported mechanism contributing to NLRP3 inflammasome 
      activation is potassium ion (K(+) ) efflux across the plasma membrane. 
      Identification of K(+) channels involved in NLRP3 activation remains incomplete. 
      Here, we investigated the role of the K(+) channel THIK-1 in NLRP3 activation. 
      Both pharmacological inhibitors and cells from THIK-1 knockout (KO) mice were 
      used to assess THIK-1 contribution to macrophage NLRP3 activation in vitro. 
      Pharmacological inhibition of THIK-1 inhibited caspase-1 activation and IL-1beta 
      release from mouse bone-marrow-derived macrophages (BMDMs), mixed glia, and 
      microglia in response to NLRP3 agonists. Similarly, BMDMs and microglia from 
      THIK-1 KO mice had reduced NLRP3-dependent IL-1beta release in response to P2X7 
      receptor activation with ATP. Overall, these data suggest that THIK-1 is a 
      regulator of NLRP3 inflammasome activation in response to ATP and identify THIK-1 
      as a potential therapeutic target for inflammatory disease.
CI  - (c) 2022 The Authors. GLIA published by Wiley Periodicals LLC.
FAU - Drinkall, Samuel
AU  - Drinkall S
AUID- ORCID: 0000-0003-0588-8494
AD  - Division of Pharmacy & Optometry, School of Health Sciences, Faculty of Biology, 
      Medicine and Health, University of Manchester, Manchester Academic Health Science 
      Centre, Manchester, UK.
FAU - Lawrence, Catherine B
AU  - Lawrence CB
AUID- ORCID: 0000-0002-2372-2968
AD  - Division of Neuroscience and Experimental Psychology, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 
      Manchester Academic Health Science Centre, Manchester, UK.
FAU - Ossola, Bernadino
AU  - Ossola B
AD  - Cerevance Ltd, Cambridge, UK.
FAU - Russell, Samuel
AU  - Russell S
AD  - Cerevance Ltd, Cambridge, UK.
FAU - Bender, Clare
AU  - Bender C
AD  - Cerevance Ltd, Cambridge, UK.
FAU - Brice, Nicola B
AU  - Brice NB
AD  - Cerevance Ltd, Cambridge, UK.
FAU - Dawson, Lee A
AU  - Dawson LA
AD  - Cerevance Ltd, Cambridge, UK.
FAU - Harte, Michael
AU  - Harte M
AD  - Division of Pharmacy & Optometry, School of Health Sciences, Faculty of Biology, 
      Medicine and Health, University of Manchester, Manchester Academic Health Science 
      Centre, Manchester, UK.
AD  - The Lydia Becker Institute of Immunology and Inflammation, University of 
      Manchester, Manchester, UK.
FAU - Brough, David
AU  - Brough D
AUID- ORCID: 0000-0002-2250-2381
AD  - Division of Neuroscience and Experimental Psychology, School of Biological 
      Sciences, Faculty of Biology, Medicine and Health, University of Manchester, 
      Manchester Academic Health Science Centre, Manchester, UK.
AD  - The Lydia Becker Institute of Immunology and Inflammation, University of 
      Manchester, Manchester, UK.
AD  - Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science 
      Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester, 
      UK.
LA  - eng
GR  - MR/N013751/1/MRC_/Medical Research Council/United Kingdom
GR  - MR/T016515/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220330
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - 0 (Inflammasomes)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Kcnk13 protein, mouse)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 (Nlrp3 protein, mouse)
RN  - 0 (Potassium Channels)
RN  - 0 (Potassium Channels, Tandem Pore Domain)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Animals
MH  - Caspase 1/metabolism
MH  - *Diabetes Mellitus, Type 2
MH  - *Inflammasomes/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism
MH  - Potassium/metabolism
MH  - Potassium Channels
MH  - Potassium Channels, Tandem Pore Domain/*metabolism
PMC - PMC9314991
OTO - NOTNLM
OT  - NLRP3
OT  - THIK-1
OT  - inflammasome
OT  - inflammation
OT  - interleukin-1
OT  - potassium channel
EDAT- 2022/03/31 06:00
MHDA- 2022/05/10 06:00
PMCR- 2022/07/26
CRDT- 2022/03/30 12:16
PHST- 2022/03/15 00:00 [revised]
PHST- 2022/01/07 00:00 [received]
PHST- 2022/03/21 00:00 [accepted]
PHST- 2022/03/31 06:00 [pubmed]
PHST- 2022/05/10 06:00 [medline]
PHST- 2022/03/30 12:16 [entrez]
PHST- 2022/07/26 00:00 [pmc-release]
AID - GLIA24174 [pii]
AID - 10.1002/glia.24174 [doi]
PST - ppublish
SO  - Glia. 2022 Jul;70(7):1301-1316. doi: 10.1002/glia.24174. Epub 2022 Mar 30.