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Two-pore potassium channel TREK-1 (K2P2.1) regulates NLRP3 inflammasome activity in macrophages.
Immanuel, Camille N; Teng, Bin; Dong, Brittany E; Gordon, Elizabeth M; Luellen, Charlean; Lopez, Benjamin; Harding, Jeffrey; Cormier, Stephania A; Fitzpatrick, Elizabeth A; Schwingshackl, Andreas; Waters, Christopher M.
Afiliación
  • Immanuel CN; Division of Pediatric Critical Care, Department of Pediatrics, Le Bonheur Children's Hospital, University of Tennessee Health Science Center, Memphis, Tennessee, United States.
  • Teng B; Department of Physiology, Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States.
  • Dong BE; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States.
  • Gordon EM; Department of Physiology, Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States.
  • Luellen C; Department of Physiology, Saha Cardiovascular Research Center, University of Kentucky, Lexington, Kentucky, United States.
  • Lopez B; Department of Physiology, University of Tennessee Health Science Center, Memphis, Tennessee, United States.
  • Harding J; Department of Pediatrics, University of California, Los Angeles, California, United States.
  • Cormier SA; Department of Biological Sciences, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, United States.
  • Fitzpatrick EA; Department of Biological Sciences, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, United States.
  • Schwingshackl A; Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, United States.
  • Waters CM; Department of Pediatrics, University of California, Los Angeles, California, United States.
Am J Physiol Lung Cell Mol Physiol ; 326(3): L367-L376, 2024 Mar 01.
Article en En | MEDLINE | ID: mdl-38252657
ABSTRACT
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-1ß, 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-1ß 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tetrahidronaftalenos / Tetrazoles / Canales de Potasio de Dominio Poro en Tándem / Inflamasomas Límite: Animals Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tetrahidronaftalenos / Tetrazoles / Canales de Potasio de Dominio Poro en Tándem / Inflamasomas Límite: Animals Idioma: En Revista: Am J Physiol Lung Cell Mol Physiol Asunto de la revista: BIOLOGIA MOLECULAR / FISIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos