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Tranilast directly targets <scp>NLRP</scp> 3 to treat inflammasome‐driven diseases
- Source :
- EMBO Molecular Medicine, EMBO Molecular Medicine, Vol 10, Iss 4, Pp n/a-n/a (2018)
- Publication Year :
- 2018
- Publisher :
- EMBO, 2018.
-
Abstract
- The dysregulation of NLRP3 inflammasome can cause uncontrolled inflammation and drive the development of a wide variety of human diseases, but the medications targeting NLRP3 inflammasome are not available in clinic. Here, we show that tranilast (TR), an old anti‐allergic clinical drug, is a direct NLRP3 inhibitor. TR inhibits NLRP3 inflammasome activation in macrophages, but has no effects on AIM2 or NLRC4 inflammasome activation. Mechanismly, TR directly binds to the NACHT domain of NLRP3 and suppresses the assembly of NLRP3 inflammasome by blocking NLRP3 oligomerization. In vivo experiments show that TR has remarkable preventive or therapeutic effects on the mouse models of NLRP3 inflammasome‐related human diseases, including gouty arthritis, cryopyrin‐associated autoinflammatory syndromes, and type 2 diabetes. Furthermore, TR is active ex vivo for synovial fluid mononuclear cells from patients with gout. Thus, our study identifies the old drug TR as a direct NLRP3 inhibitor and provides a potentially practical pharmacological approach for treating NLRP3‐driven diseases.
- Subjects :
- Male
0301 basic medicine
Medicine (General)
Inflammasomes
Tranilast
Immunology
Enzyme-Linked Immunosorbent Assay
Inflammation
QH426-470
Mice
03 medical and health sciences
AIM2
R5-920
NLRP3
Chlorides
NLRC4
In vivo
NLR Family, Pyrin Domain-Containing 3 Protein
Genetics
directly bind
Animals
Humans
Immunoprecipitation
Medicine
ortho-Aminobenzoates
Pharmacology & Drug Discovery
Research Articles
integumentary system
business.industry
HEK 293 cells
Inflammasome
tranilast
inhibitor
DNA-Binding Proteins
Mice, Inbred C57BL
HEK293 Cells
030104 developmental biology
NACHT domain
Potassium
Cancer research
Molecular Medicine
inflammasome‐driven diseases
medicine.symptom
business
Research Article
medicine.drug
Subjects
Details
- ISSN :
- 17574684 and 17574676
- Volume :
- 10
- Database :
- OpenAIRE
- Journal :
- EMBO Molecular Medicine
- Accession number :
- edsair.doi.dedup.....77659eefe6d03afff5acc59359fdc6dc