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Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation
- Source :
- Journal of Biological Chemistry. 289:13937-13947
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- 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.
- Subjects :
- Lung Diseases
Inflammasomes
animal diseases
Interleukin-1beta
Immunology
Caspase 1
chemical and pharmacologic phenomena
Inflammation
Biochemistry
Mice
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Macrophage
Molecular Biology
Caspase
Cell Size
Water transport
Aquaporin 1
biology
urogenital system
Macrophages
Water
Interleukin
Biological Transport
Inflammasome
Cell Biology
biochemical phenomena, metabolism, and nutrition
Cell biology
Enzyme Activation
Solubility
biology.protein
bacteria
Female
medicine.symptom
Carrier Proteins
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 289
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....bb95666c4c1ceda009fac50a6e9572db