Back to Search
Start Over
Crucial role of NLRP3 inflammasome in a murine model of Kawasaki disease
- Source :
- Journal of molecular and cellular cardiology. 138
- Publication Year :
- 2019
-
Abstract
- Kawasaki disease (KD) is a systemic febrile syndrome during childhood that is characterized by coronary arteritis. The etiopathogenesis of KD remains to be elucidated. NLRP3 inflammasome is a large multiprotein complex that plays a key role in IL-1β-driven sterile inflammatory diseases. In the present study, we investigated the role of NLRP3 inflammasome in a murine model of KD induced by Candida albicans water-soluble fraction (CAWS) and found that NLRP3 inflammasome is required for the development of CAWS-induced vasculitis. CAWS administration induced IL-1β production, caspase-1 activation, leukocyte infiltration, and fibrotic changes in the aortic root and coronary arteries, which were significantly inhibited by a deficiency of IL-1β, NLRP3, and ASC. In vitro experiments showed that among cardiac resident cells, macrophages, but not endothelial cells or fibroblasts, expressed Dectin-2, but did not produce IL-1β in response to CAWS. In contrast, CAWS induced caspase-1 activation and IL-1β production in bone marrow-derived dendritic cells (BMDCs), which were inhibited by a specific caspase-1 inhibitor and a deficiency of NLRP3, ASC, and caspase-1. CAWS induced NLRP3 and pro-IL-1β expression through a Dectin-2/Syk/JNK/NF-κB pathway, and caspase-1 activation and cleavage of pro-IL-1β through Dectin-2/Syk/JNK-mediated mitochondrial ROS generation, indicating that CAWS induces the priming and activation of NLRP3 inflammasome in BMDCs. These findings provide new insights into the pathogenesis of KD vasculitis, and suggest that NLRP3 inflammasome may be a potential therapeutic target for KD.
- Subjects :
- 0301 basic medicine
Mitochondrial ROS
Vasculitis
Inflammasomes
Interleukin-1beta
Syk
Priming (immunology)
Inflammation
030204 cardiovascular system & hematology
Mucocutaneous Lymph Node Syndrome
Pathogenesis
03 medical and health sciences
0302 clinical medicine
Candida albicans
NLR Family, Pyrin Domain-Containing 3 Protein
medicine
Animals
Molecular Biology
integumentary system
Chemistry
Myocardium
Caspase 1
Inflammasome
Dendritic Cells
medicine.disease
In vitro
Mice, Inbred C57BL
Disease Models, Animal
030104 developmental biology
Immunology
medicine.symptom
Cardiology and Cardiovascular Medicine
medicine.drug
Signal Transduction
Subjects
Details
- ISSN :
- 10958584
- Volume :
- 138
- Database :
- OpenAIRE
- Journal :
- Journal of molecular and cellular cardiology
- Accession number :
- edsair.doi.dedup.....e00f122f7d37c52c3cb7aebd0eee56cb