Knockdown of TRIM22 Relieves Oxygen–Glucose Deprivation/Reoxygenation-Induced Apoptosis and Inflammation Through Inhibition of NF-κB/NLRP3 Axis

Abstract

Tripartite motif-containing 22 (TRIM22) has been documented to participate in numerous cellular activities during human diseases. However, whether TRIM22 is involved in the regulation of neuronal survival during the progression of cerebral ischemia/reperfusion (I/R) injury remains unknown. In the present study, treatment of HCN-2 cells with oxygen–glucose deprivation/reoxygenation (OGD/R) markedly upregulated TRIM22 expression. A significant increase in TRIM22 expression was observed in the ischemic cortex tissues from middle cerebral artery occlusion/reperfusion mice. OGD/R inhibited the viability and induced the apoptosis of HCN-2 cells, which was accompanied by an increase in caspase-3 activity and an increase in LDH release. Furthermore, OGD/R increased the levels of tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, and monocyte chemoattractant protein-1 and induced NLRP3 inflammasome activation, as evidenced by increases in NACHT, LRR and PYD domains-containing protein 3, apoptosis-associated speck-like protein containing a caspase recruitment domain and cleaved caspase-1 expression and caspase-1 activity. However, these changes induced by OGD/R were blocked by silencing of TRIM22. In addition, TRIM22 regulated NF-κB activity in HCN-2 cells undergoing OGD/R stimulation. Furthermore, inhibition of NF-κB by pyrrolidine dithiocarbamate inhibited OGD/R-induced NLRP3 inflammasome activation in HCN-2 cells. Taken together, silencing of TRIM22 protects neurons against OGD/R-induced apoptosis and inflammation. The anti-inflammatory effect of TRIM22 knockdown was the consequence of inhibition of NF-κB/NLRP3 axis. TRIM22 may be a potential target for treating cerebral I/R injury.

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Abbreviations

TRIM22:

Tripartite motif-containing 22

I/R:

Ischemia/reperfusion

LDH:

Lactate dehydrogenase

NF-κB:

Nuclear factor-κB

OGD/R:

Oxygen–glucose deprivation/reoxygenation

TNF-α:

Tumor necrosis factor-alpha

IL-1β:

Interleukin-1 beta

NLRP3:

Nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3

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Acknowledgements

This work was supported by High level cultivation fund of Henan University of Science and Technology (2015GJB021) and Project fund of science and technology department of henan province (164102310412).

Funding

This work was supported by High level cultivation fund of Henan University of Science and Technology (2015GJB021) and Project fund of science and technology department of henan province (164102310412).

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All authors contributed to the study conception and design. CK, GZ and YC performed cellular and molecular experiments in the research. Material preparation, data collection and analysis were performed by CK, YC and YW. The first draft of the manuscript was written by CK and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhaofeng Lu.

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Animal experiments in this study were approved by the Institutional Animal Care and Use Committee of First Affiliated Hospital of Henan University of Science and Technology.

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Kang, C., Lu, Z., Zhu, G. et al. Knockdown of TRIM22 Relieves Oxygen–Glucose Deprivation/Reoxygenation-Induced Apoptosis and Inflammation Through Inhibition of NF-κB/NLRP3 Axis. Cell Mol Neurobiol 41, 341–351 (2021). https://doi.org/10.1007/s10571-020-00855-w

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Keywords

  • Tripartite motif-containing 22
  • Cerebral ischemia/reperfusion injury
  • Nuclear factor-κb
  • Nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3