PMID- 38252657
OWN - NLM
STAT- MEDLINE
DCOM- 20240307
LR  - 20240307
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 326
IP  - 3
DP  - 2024 Mar 1
TI  - Two-pore potassium channel TREK-1 (K2P2.1) regulates NLRP3 inflammasome activity 
      in macrophages.
PG  - L367-L376
LID - 10.1152/ajplung.00313.2023 [doi]
AB  - Because of the importance of potassium efflux in inflammasome activation, we 
      investigated the role of the two-pore potassium (K2P) channel TREK-1 in 
      macrophage inflammasome activity. Using primary alveolar macrophages (AMs) and 
      bone marrow-derived macrophages (BMDMs) from wild-type (wt) and TREK-1(-/-) mice, 
      we measured responses to inflammasome priming [using lipopolysaccharide (LPS)] 
      and activation (LPS + ATP). We measured IL-1beta, caspase-1, and NLRP3 via ELISA and 
      Western blot. A membrane-permeable potassium indicator was used to measure 
      potassium efflux during ATP exposure, and a fluorescence-based assay was used to 
      assess changes in membrane potential. Inflammasome activation induced by 
      LPS + ATP increased IL-1beta secretion in wt AMs, whereas activation was 
      significantly reduced in TREK-1(-/-) AMs. Priming of BMDMs using LPS was not 
      affected by either genetic deficiency or pharmacological inhibition of TREK-1 
      with Spadin. Cleavage of caspase-1 following LPS + ATP treatment was 
      significantly reduced in TREK-1(-/-) BMDMs. The intracellular potassium 
      concentration in LPS-primed wt BMDMs was significantly lower compared with 
      TREK-1(-/-) BMDMs or wt BMDMs treated with Spadin. Conversely, activation of 
      TREK-1 with BL1249 caused a decrease in intracellular potassium in wt BMDMs. 
      Treatment of LPS-primed BMDMs with ATP caused a rapid reduction in intracellular 
      potassium levels, with the largest change observed in TREK-1(-/-) BMDMs. 
      Intracellular K(+) changes were associated with changes in the plasma membrane 
      potential (Em), as evidenced by a more depolarized Em in TREK-1(-/-) BMDMs 
      compared with wt, and Em hyperpolarization upon TREK-1 channel opening with 
      BL1249. These results suggest that TREK-1 is an important regulator of NLRP3 
      inflammasome activation in macrophages.NEW & NOTEWORTHY Because of the importance 
      of potassium efflux in inflammasome activation, we investigated the role of the 
      two-pore potassium (K2P) channel TREK-1 in macrophage inflammasome activity. 
      Using primary alveolar macrophages and bone marrow-derived macrophages from 
      wild-type and TREK-1(-/-) mice, we measured responses to inflammasome priming 
      (using LPS) and activation (LPS + ATP). Our results suggest that TREK-1 is an 
      important regulator of NLRP3 inflammasome activation in macrophages.
FAU - Immanuel, Camille N
AU  - Immanuel CN
AD  - Division of Pediatric Critical Care, Department of Pediatrics, Le Bonheur 
      Children's Hospital, University of Tennessee Health Science Center, Memphis, 
      Tennessee, United States.
AD  - Department of Physiology, Saha Cardiovascular Research Center, University of 
      Kentucky, Lexington, Kentucky, United States. ROR: https://ror.org/02k3smh20
FAU - Teng, Bin
AU  - Teng B
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      Tennessee, United States.
FAU - Dong, Brittany E
AU  - Dong BE
AD  - Department of Physiology, Saha Cardiovascular Research Center, University of 
      Kentucky, Lexington, Kentucky, United States. ROR: https://ror.org/02k3smh20
FAU - Gordon, Elizabeth M
AU  - Gordon EM
AD  - Department of Physiology, Saha Cardiovascular Research Center, University of 
      Kentucky, Lexington, Kentucky, United States. ROR: https://ror.org/02k3smh20
FAU - Luellen, Charlean
AU  - Luellen C
AD  - Department of Physiology, University of Tennessee Health Science Center, Memphis, 
      Tennessee, United States.
FAU - Lopez, Benjamin
AU  - Lopez B
AD  - Department of Pediatrics, University of California, Los Angeles, California, 
      United States.
FAU - Harding, Jeffrey
AU  - Harding J
AD  - Department of Biological Sciences, Pennington Biomedical Research Center, 
      Louisiana State University, Baton Rouge, Louisiana, United States.
FAU - Cormier, Stephania A
AU  - Cormier SA
AD  - Department of Biological Sciences, Pennington Biomedical Research Center, 
      Louisiana State University, Baton Rouge, Louisiana, United States.
FAU - Fitzpatrick, Elizabeth A
AU  - Fitzpatrick EA
AD  - Department of Microbiology, Immunology, and Biochemistry, University of Tennessee 
      Health Science Center, Memphis, Tennessee, United States.
FAU - Schwingshackl, Andreas
AU  - Schwingshackl A
AUID- ORCID: 0000-0002-5608-0199
AD  - Department of Pediatrics, University of California, Los Angeles, California, 
      United States.
FAU - Waters, Christopher M
AU  - Waters CM
AUID- ORCID: 0000-0002-6706-1284
AD  - Department of Physiology, Saha Cardiovascular Research Center, University of 
      Kentucky, Lexington, Kentucky, United States. ROR: https://ror.org/02k3smh20
LA  - eng
GR  - HL151419/HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/
GR  - HL131526/HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/
GR  - HL123540/HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/
GR  - HL146821/HHS | NIH | National Heart, Lung, and Blood Institute (NHLBI)/
GR  - IA-678511/American Lung Association (ALA)/
GR  - 20TPA35490010/American Heart Association (AHA)/
GR  - Le Bonheur Children's Hospital/
PT  - Journal Article
DEP - 20240122
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Inflammasomes)
RN  - 0 (NLR Family, Pyrin Domain-Containing 3 Protein)
RN  - 0 ((5,6,7,8-tetrahydronaphthalen-1-yl)-(2-(1H-tetrazol-5-yl)phenyl)amine)
RN  - 0 (potassium channel protein TREK-1)
RN  - RWP5GA015D (Potassium)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Potassium Channels, Tandem Pore Domain)
RN  - EC 3.4.22.36 (Caspase 1)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (Tetrazoles)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Inflammasomes/metabolism
MH  - NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
MH  - Potassium/metabolism
MH  - Lipopolysaccharides/pharmacology/metabolism
MH  - Mice, Knockout
MH  - *Potassium Channels, Tandem Pore Domain/genetics/metabolism
MH  - Macrophages/metabolism
MH  - Caspase 1/metabolism
MH  - Adenosine Triphosphate/pharmacology/metabolism
MH  - Interleukin-1beta/metabolism
MH  - *Tetrahydronaphthalenes
MH  - *Tetrazoles
OTO - NOTNLM
OT  - K2P2.1
OT  - NLRP3
OT  - acute respiratory distress syndrome (ARDS)
OT  - inflammasome
OT  - two-pore potassium channel (TREK-1)
EDAT- 2024/01/22 18:42
MHDA- 2024/03/07 06:43
CRDT- 2024/01/22 13:35
PHST- 2024/03/07 06:43 [medline]
PHST- 2024/01/22 18:42 [pubmed]
PHST- 2024/01/22 13:35 [entrez]
AID - 10.1152/ajplung.00313.2023 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2024 Mar 1;326(3):L367-L376. doi: 
      10.1152/ajplung.00313.2023. Epub 2024 Jan 22.