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MiR-223-3p inhibits rTp17-induced inflammasome activation and pyroptosis by targeting NLRP3

Long, Fu‐quan, Kou, Cai‐xia, Li, Ke, Wu, Juan, Wang, Qian‐qiu·2020·Journal of Cellular and Molecular Medicine
DOI 10.1111/jcmm.16061PMC PMC7754033
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Abstract

The incidence of syphilis caused by Treponema pallidum subsp pallidum (T pallidum) infection is accompanied by inflammatory injuries of vascular endothelial cells. Studies have revealed that T pallidum infection could induce inflammasome activation and pyroptosis in macrophages. MicroRNA‐223‐3p (miR‐223‐3p) was reported to be a negative regulator in inflammatory diseases. The present study aimed to explore whether miR‐223‐3p regulates T pallidum‐induced inflammasome activation and pyroptosis in vascular endothelial cells, and determine the mechanisms which underlie this process. MiR‐223‐3p levels in syphilis and control samples were determined. The biological function of miR‐223‐3p in the NLRP3 inflammasome and pyroptosis was evaluated in T pallidum‐infected human umbilical vein endothelial cells (HUVECs). We observed a dramatic decrease in miR‐223‐3p levels in syphilis patients (n = 20) when compared to healthy controls (n = 20). Moreover, miR‐223‐3p showed a notable inhibitory effect on recombinant Tp17 (rTP17)‐induced caspase‐1 activation, resulting in decrease in IL‐1β production and pyroptosis, which was accompanied by the release of lactate dehydrogenase (LDH) in HUVECs. Additionally, the dual‐luciferase assay confirmed that NLRP3 is a direct target of miR‐223‐3p. Moreover, NLRP3 overexpression or knockdown largely blocked the effects of miR‐223‐3p on T pallidum‐induced inflammasome activation and pyroptosis in HUVECs. Most importantly, a notable negative correlation was observed between miR‐223‐3p and NLRP3, caspase‐1, and IL‐1β, respectively, in the serum of syphilis patients and healthy controls. Taken together, our results reveal that miR‐223‐3p targets NLRP3 to suppress inflammasome activation and pyroptosis in T pallidum‐infected endothelial cells, implying that miR‐223‐3p could be a potential target for syphilis patients.

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  • miR-223-3p represses NLRP3 and limits inflammasome activation in myeloid and microglial models.

    “Additionally, miR-223-3p has been shown to repress NLRP3 and limit inflammasome activation in myeloid and microglial models (Bauernfeind et al., 2012; Long et al., 2020).”

    From Cell-specific MicroRNA networks orchestrate the pathogenesis of Alzheimer’s disease (2026) · cites this paper as Long et al., 2020

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Cited by

Sorted by citations

Authors
Long, F., Kou, C., Li, K., Wu, J., & Wang, Q.
Affiliations
  • Department of STD Shanghai Skin Disease Hospital Tongji University School of Medicine Shanghai China
  • Institute of Dermatology Chinese Academy of Medical Sciences and Peking Union Medical College Nanjing China
ORCID
Long, Fu‐quan
Venue
Journal of Cellular and Molecular Medicine
Publisher
Wiley
Published
2020-11-03
Volume
24
Issue
24
Pages
14405-14414
ISSN
  • 1582-1838
  • 1582-4934
DOI
10.1111/jcmm.16061
PMC
PMC7754033
Cited by
70
References
0
Language
en
Licence
creativecommons.org/licenses/by/4.0/ (vor)
Funders
Natural Science Foundation of Shanghai (14ZR1437100)

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