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Activation and Measurement of NLRP3 Inflammasome Activity Using IL-1β in Human Monocyte-derived Dendritic Cells
Published on: May 22, 2014
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Soluble Uric Acid Activates the NLRP3 Inflammasome
Tarcio Teodoro Braga1,2, Maria Fernanda Forni3, Matheus Correa-Costa1
1Laboratory of Transplantation Immunobiology, Department of Immunology, Institute of Biomedical Sciences IV, University of São Paulo (USP), São Paulo, Brazil.
Scientific Reports
|January 14, 2017
Summary
Soluble uric acid (sUA) activates the NLRP3 inflammasome, inducing IL-1β release and mitochondrial dysfunction. Blocking sUA may offer new therapies for renal fibrosis.
Area of Science:
- Immunology
- Cell Biology
- Pathology
Background:
- Uric acid is a damage-associated molecular pattern (DAMP).
- Crystallized uric acid activates the NLRP3 inflammasome.
- High serum soluble uric acid (sUA) occurs in diseases before crystal formation.
Purpose of the Study:
- To investigate if soluble uric acid (sUA) activates the NLRP3 inflammasome.
- To determine if sUA induces IL-1β production.
- To explore the role of sUA in a disease model of renal fibrosis.
Main Methods:
- Macrophages were stimulated with sUA to monitor ROS, mitochondrial parameters, IL-1β release, ASC speck formation, and caspase-1 activation.
- Nlrp3-/- and Myd88-/- macrophages were compared to wild-type (WT) cells.
- A disease model with elevated sUA levels was used to assess correlations.
Main Results:
- sUA induced IL-1β release, mitochondrial ROS production, ASC speck formation, and caspase-1 activation.
- Nlrp3-/- macrophages showed improved redox state and mitochondrial respiration.
- A correlation was observed between sUA levels, inflammasome activation, and fibrosis in vivo.
Conclusions:
- Soluble uric acid (sUA) activates the NLRP3 inflammasome and contributes to renal fibrosis.
- Therapeutic strategies targeting sUA or its recognition by phagocytes are proposed for renal fibrosis.
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