Macrophages monitor tissue osmolarity and induce inflammatory response through NLRP3 and NLRC4 inflammasome activation
Autor: | Ruslan Medzhitov, W. K. Eddie Ip |
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Rok vydání: | 2015 |
Předmět: |
Osmotic shock
Inflammasomes Interleukin-1beta Caspase 1 General Physics and Astronomy Inflammation Biology Article General Biochemistry Genetics and Molecular Biology Osmotic Pressure NLRC4 NLR Family Pyrin Domain-Containing 3 Protein medicine Animals Sodium Chloride Dietary Multidisciplinary Innate immune system Osmotic concentration Macrophages Calcium-Binding Proteins Osmolar Concentration Mitophagy Inflammasome General Chemistry Mitochondria Enzyme Activation Mice Inbred C57BL Immunology Th17 Cells medicine.symptom Apoptosis Regulatory Proteins Carrier Proteins Reactive Oxygen Species Homeostasis medicine.drug |
Zdroj: | Nature communications |
ISSN: | 2041-1723 |
Popis: | Interstitial osmolality is a key homeostatic variable that varies depending on the tissue microenvironment. Mammalian cells have effective mechanisms to cope with osmotic stress by engaging various adaptation responses. Hyperosmolality due to high dietary salt intake has been linked to pathological inflammatory conditions. Little is known about the mechanisms of sensing the hyperosmotic stress by the innate immune system. Here we report that caspase-1 is activated in macrophages under hypertonic conditions. Mice with high dietary salt intake display enhanced induction of Th17 response upon immunization, and this effect is abolished in caspase-1-deficient mice. Our findings identify an unknown function of the inflammasome as a sensor of hyperosmotic stress, which is crucial for the induction of inflammatory Th17 response. |
Databáze: | OpenAIRE |
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