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BMC Immunology

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Open Access 01-12-2022 | Polymyositis | Research

NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis

Authors: Ping Xia, Yu-Quan Shao, Cong-Cong Yu, Yu Xie, Zhi-Jie Zhou

Published in: BMC Immunology | Issue 1/2022

Abstract

Objective

This study was designed to investigate the role of the nucleotide-binding-domain -and leucine-rich repeat -containing (NLR) family, pyrin-domain-containing 3 (NLRP3) inflammasome in the pathogenesis of polymyositis (PM).

Methods

Immunochemistry was performed to analyze the NLRP3, caspase-1 and interleukin-1 beta (IL-1β) expression in the muscle tissue of PM patients. Rat model of PM and C2C12 cell were used to investigate the potential role of NLRP3 inflammasome in PM.

Results

The percentage of CD 68+ macrophages, and the expression levels of NLRP3, caspase-1 and IL-1β in the muscle tissue were elevated in 27 PM patients. LPS/ATP treatment resulted in activation of NLRP3 inflammasome and secretion of IL-1β as well as interferons (IFNs) and monocyte chemotactic protein-1 (MCP-1) in the Raw 264.7 macrophages. Meanwhile, LPS/ATP challenged activation of NLRP3 inflammasome induced overexpression of major histocompatibility complex class I (MHC-I), a key molecular of PM in the co-cultured C2C12 cells. The effect was decreased by treatment of NLRP3 inflammasome inhibitor MCC950 or siRNA of NLRP3 inflammasome. These findings suggested certain levels of IL-1β rather than IFNs up-regulated MHC-I expression in C2C12 cells. IL-1β blockade using neutralizing IL-1β monoclonal antibody or siRNA of IL-1β suppressed MHC-I overexpression. In vivo, NLRP3 inflammasome inhibition by MCC950 reduced the expression of NLRP3, IL-1β and MHC-I in the muscle tissue of PM modal rats. Also, it attenuated the intensity of muscle inflammation as well as the CRP, CK, and LDH levels in the serum.

Conclusion

NLRP3/caspase-1/IL-1β axis may play an important role in the development of PM. Inhibition of NLRP3 activation may hold promise in the treatment of PM.

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Title: NLRP3 inflammasome up-regulates major histocompatibility complex class I expression and promotes inflammatory infiltration in polymyositis
Authors: Ping Xia
Yu-Quan Shao
Cong-Cong Yu
Yu Xie
Zhi-Jie Zhou
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Polymyositis
Polymyositis
Interferon
Published in: BMC Immunology / Issue 1/2022
Electronic ISSN: 1471-2172
DOI: https://doi.org/10.1186/s12865-022-00515-2

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