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Liver X receptors agonists suppress NLRP3 inflammasome activation
- Source :
- Cytokine. 91
- Publication Year :
- 2016
-
Abstract
- Inflammasomes are multiprotein complexes that control the production of IL-1β and IL-18. NLRP3 inflammasome, the most characterized inflammasome, plays prominent roles in defense against infection, however aberrant activation is deleterious and leads to diseases. Therefore, its tight control offers therapeutic promise. Liver X receptors (LXRs) have significant anti-inflammatory properties. Whether LXRs regulate inflammasome remains unresolved. We thus tested the hypothesis that LXR's anti-inflammatory properties may result from its ability to suppress inflammasome activation. In this study, LXRs agonists inhibited the induction of IL-1β production, caspase-1 cleavage and ASC oligomerization by NLRP3 inflammasome. The agonists also inhibited inflammasome-associated mtROS production. Importantly, the agonists inhibited the priming of inflammasome activation. In vivo data also showed that LXRs agonist prevented NLRP3-dependent peritonitis. In conclusion, LXRs agonists are identified to potently suppress NLRP3 inflammasome and the regulation of LXRs signaling is a potential therapeutic for inflammasome-driven diseases.
- Subjects :
- 0301 basic medicine
Agonist
medicine.medical_specialty
medicine.drug_class
Inflammasomes
Immunology
Interleukin-1beta
Inflammation
Biology
Peritonitis
Biochemistry
Cell Line
03 medical and health sciences
Mice
In vivo
Internal medicine
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Immunology and Allergy
Animals
Liver X receptor
Molecular Biology
Liver X Receptors
Caspase 3
Inflammasome
Hematology
Cell biology
030104 developmental biology
Endocrinology
NLRP3 inflammasome activation
medicine.symptom
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 10960023
- Volume :
- 91
- Database :
- OpenAIRE
- Journal :
- Cytokine
- Accession number :
- edsair.doi.dedup.....280b08e40dd865f9b42fb44198717990