期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 289, 期 20, 页码 13937-13947出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M113.534594
关键词
Aquaporin; Caspase; Inflammation; Interleukin; Water Channel; RVD; Cell Swelling; Inflammasome
资金
- Programme d'excellence Marshall Diane convention
- Fonds de la Recherche Scientifique Medicale (FRSM)
- Actions de Recherche Concertees
- Communaute Francaise de Belgique
- Direction de la Recherche Scientifique [ARC 09/14-021]
- Fondation Contre le Cancer
- Fonds de la Recherche Scientifique (FNRS) [PDR T.0119.13 14633768]
- European Commission [202047]
- Agence Nationale de Securite Sanitaire de L'Alimentation, de l'Environnement, et du Travail (ANSES, France)
- Fondation Saint-Luc at Universite Catholique de Louvain
- Baxter extramural grant
- NCCR Kidney
- CH program (Swiss National Science Foundation)
- Swiss National Science Foundation [310030-146490]
Background: Aquaporins are channels permeable to water, and they are essential for immune cell migration. Results: We demonstrate that aquaporin-mediated water fluxes are necessary for the NLRP3 inflammasome-dependent release of mature IL-1 in vitro and in vivo. Conclusion: Aquaporins are implicated in the mechanisms of proinflammatory cytokine secretion during inflammation. Significance: The discovery of a new function for AQPs opens new diagnostic and therapeutic opportunities in inflammatory disorders. 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-1 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-1 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-1 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.
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