Critical role of aquaporins in interleukin 1β (IL-1β)-induced inflammation.
Rapid changes in cell volume characterize macrophage activation, but the role of water channels in inflammation remains unclear. We show here that, in vitro, aquaporin (AQP) blockade or deficiency results in reduced IL-1β release by macrophages activated with a variety of NLRP3 activators. Inhibition of AQP specifically during the regulatory volume decrease process is sufficient to limit IL-1β release by macrophages through the NLRP3 inflammasome axis. The immune-related activity of AQP was confirmed in vivo in a model of acute lung inflammation induced by crystals. AQP1 deficiency is associated with a marked reduction of both lung IL-1β release and neutrophilic inflammation. We conclude that AQP-mediated water transport in macrophages constitutes a general danger signal required for NLRP3-related inflammation. Our findings reveal a new function of AQP in the inflammatory process and suggest a novel therapeutic target for anti-inflammatory therapy.
From the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) and.
Virginie
V
Rabolli
From the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) and.
Laurent
L
Wallemme
From the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) and.
Sandra
S
Lo Re
From the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) and.
Francine
F
Uwambayinema
From the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) and.
Mihaly
M
Palmai-Pallag
the Center for Surface Chemistry and Catalysis, Katholieke Universiteit Leuven, 3001 Heverlee, Belgium, and.
Leen
L
Thomassen
Cell Biology Unit, de Duve Institute, and.
Donatienne
D
Tyteca
Institute of NeuroScience (IoNS), Université Catholique de Louvain, 1200 Brussels, Belgium.
Jean-Noel
JN
Octave
Cell Biology Unit, de Duve Institute, and.
Etienne
E
Marbaix
From the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) and.
Dominique
D
Lison
the Institute of Physiology, Zurich Center for Integrative Human Physiology, University of Zurich, 8006 Zurich, Switzerland Division of Nephrology, Institut de Recherche Experimentale et Clinique (IREC).
Olivier
O
Devuyst
From the Louvain Centre for Toxicology and Applied Pharmacology (LTAP) and francois.huaux@uclouvain.be.
François
F
Huaux
D000818:Animals; D051398:Aquaporin 1 / Q000378:metabolism*; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D020170:Caspase 1 / Q000378:metabolism; D048429:Cell Size; D004789:Enzyme Activation; D005260:Female; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D008171:Lung Diseases / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D015398:Signal Transduction; D012995:Solubility; D014867:Water / Q000378:metabolism
D002352:Carrier Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D014867:Water; D051398:Aquaporin 1; D020170:Caspase 1
Aquaporin; Caspase; Cell Swelling; Inflammasome; Inflammation; Interleukin; RVD; Water Channel