HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-κB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function

Joint Authors

Tang, Huan
Liu, Jianping
Ren, Long
Gao, Wei
Huang, Qiushi
Mu, Heng
Qin, Ting
Long, Fan
Zeng, Mei

Source

Oxidative Medicine and Cellular Longevity

Issue

Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-16, 16 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2020-12-31

Country of Publication

Egypt

No. of Pages

16

Main Subjects

Biology

Abstract EN

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 gout.

HSP60 expression was detected in peripheral blood mononuclear cells (PBMCs) and plasma of gout patients.

The effect and molecular 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).

HSP60 expression was significantly upregulated in the PBMCs and sera of patients with acute gout (AG) compared to those with intercritical gout (IG) or healthy controls (HCs).

MSU crystals induced the expression and secretion of HSP60 in the macrophages.

HSP60 knockdown or overexpression 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 mouse models pretreated with HSP60 vivo-morpholino, paw swelling, myeloperoxidase (MPO) activity, and inflammatory cell infiltration significantly decreased.

Our study reveals that MSU crystal stimulates the expression of HSP60, which accelerates the TLR4-MyD88-NF-κB signaling pathway and exacerbates mitochondrial dysfunction.

American Psychological Association (APA)

Huang, Qiushi& Gao, Wei& Mu, Heng& Ren, Long& Tang, Huan& Liu, Jianping…[et al.]. 2020. HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-κB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1205679

Modern Language Association (MLA)

Tang, Huan…[et al.]. HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-κB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-16.
https://search.emarefa.net/detail/BIM-1205679

American Medical Association (AMA)

Huang, Qiushi& Gao, Wei& Mu, Heng& Ren, Long& Tang, Huan& Liu, Jianping…[et al.]. HSP60 Regulates Monosodium Urate Crystal-Induced Inflammation by Activating the TLR4-NF-κB-MyD88 Signaling Pathway and Disrupting Mitochondrial Function. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-16.
https://search.emarefa.net/detail/BIM-1205679

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1205679