The two pore potassium channel THIK-1 regulates NLRP3 inflammasome activation.
Glia
; 70(7): 1301-1316, 2022 07.
Article
in En
| MEDLINE
| ID: mdl-35353387
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-1ß 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-1ß 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-1ß 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Potassium Channels, Tandem Pore Domain
/
Diabetes Mellitus, Type 2
/
Inflammasomes
Limits:
Animals
Language:
En
Journal:
Glia
Journal subject:
NEUROLOGIA
Year:
2022
Document type:
Article
Country of publication:
United States