Back to Search
Start Over
HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-κB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function
- Source :
- Oxidative Medicine and Cellular Longevity, Oxidative Medicine and Cellular Longevity, Vol 2020 (2020)
- Publication Year :
- 2020
- Publisher :
- Hindawi Limited, 2020.
-
Abstract
- Background Acute gout is an inflammatory response induced by monosodium urate (MSU) crystals. HSP60 is a highly conserved stress protein that acts as a cellular “danger” signal for immune reactions. In this study, we aimed to investigate the role and molecular mechanism of HSP60 in the gout. Methods HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients. The effect and mechanism of HSP60 in gout were studied in MSU crystals treatment macrophages and C57BL/6 mice. JC-1 probe and MitoSOX Red were used to measure the mitochondrial membrane potential (MMP) and mitochondrial reactive oxygen species (mtROS). Results HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with inter-critical gout (IG) or healthy controls (HCs). MSU crystals induced expression and secretion of HSP60 in the macrophages. HSP60 knockdown or over-expression affects TLR4 and MyD88 expression, IκBα degradation and the nuclear localization of NF-κB in MSU crystal-stimulated inflammation. Further, HSP60 facilitates MMP collapse and mtROS production, and activates the NLRP3 inflammasome in MSU crystal-stimulated macrophages. In MSU crystal-induced arthritis and peritonitis mouse models pre-treated with HSP60 vivo-morpholino, paw swelling, ankle joint swelling, myeloperoxidase (MPO) activity and inflammatory cell infiltration significantly decreased. Conclusion Our study revealed that MSU crystal stimulates the expression of HSP60 which accelerates TLR4-MyD88-NF-κB signaling pathway and exacerbates mitochondrial dysfunction.
- Subjects :
- Male
0301 basic medicine
Aging
Gout
Inflammasomes
Biochemistry
Antioxidants
Mice
0302 clinical medicine
biology
Chemistry
NF-kappa B
Inflammasome
General Medicine
Middle Aged
Mitochondria
Myeloperoxidase
HSP60
Signal transduction
medicine.symptom
Signal Transduction
Research Article
medicine.drug
Adult
animal structures
Article Subject
chemical and pharmacologic phenomena
Inflammation
complex mixtures
03 medical and health sciences
medicine
Animals
Humans
Secretion
030203 arthritis & rheumatology
QH573-671
Macrophages
fungi
Chaperonin 60
Cell Biology
Arthritis, Experimental
Molecular biology
Uric Acid
Mice, Inbred C57BL
Toll-Like Receptor 4
IκBα
030104 developmental biology
Case-Control Studies
Myeloid Differentiation Factor 88
Leukocytes, Mononuclear
TLR4
biology.protein
Cytology
Subjects
Details
- ISSN :
- 19420994 and 19420900
- Volume :
- 2020
- Database :
- OpenAIRE
- Journal :
- Oxidative Medicine and Cellular Longevity
- Accession number :
- edsair.doi.dedup.....6702436c6cace5e44063e787f7538ae5