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STAMP2 alleviates microglial neurotoxicity by inhibiting LPS-induced NF-κB activation

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Abstract

Background

The six-transmembrane protein of the prostate 2 (STAMP2) is crucial for damage-induced inflammation. Excessive inflammatory responses in microglia have been discovered as the critical factor in triggering neurological diseases. However, inconclusive evidence suggests that STAMP2 alleviates neuroinflammatory diseases by regulating the inflammatory state of microglia.

Objectives

To ascertain whether the favorable effects of STAMP2 on neuroinflammation act through microglia.

Results

STAMP2 served as an anti-inflammatory modulator to inhibit the production of inflammatory and reactive oxygen species (ROS) factors and attenuated neurotoxicity. Downregulation of STAMP2 increased the levels of IL-1β, IL-6, ROS, and glutamate, and exogenous STAMP2 knock-in rescued both the exacerbated inflammation and oxidative stress induced by STAMP2 knockdown in BV-2 cells. Mechanistic study showed that STAMP2 siRNA accelerated the expression of p-P65 and p-IkBα, whereas STAMP2OE interrupted the NF-kB translocation. In addition, STAMP2 could reduce neurotoxicity by promoting cell survival and suppressing apoptosis.

Conclusion

These findings revealed that STAMP2 is involved in regulating the LPS-NF-kB signal pathway to modulate inflammatory processes in microglia cells, which could represent a possible therapeutic therapy for neurodegenerative disorders.

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Data availability

The authors declare that all data supporting the findings of this study are available within the paper and any raw data can be obtained from the corresponding author upon request.

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Acknowledgements

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Funding

No funding was used in this study.

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Authors and Affiliations

  1. Department of Radiation Oncology, Wenzhou Central Hospital, Wenzhou, 325000, Zhejiang, China

    Zengbian Chen

  2. Department of Neurology, Wenzhou Central Hospital, No. 252 Baili East Road, Lucheng District, Wenzhou, 325000, Zhejiang, China

    Jie Jin & Qi Lu

Authors
  1. Zengbian Chen
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  2. Jie Jin
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  3. Qi Lu
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Contributions

ZC and JJ designed the study and carried them out, ZC and JJ supervised the data collection, analyzed the data, and interpreted the data, ZC, JJ and QL prepared the manuscript for publication and reviewed the draft of the manuscript. All the authors have read and approved the manuscript.

Corresponding author

Correspondence to Jie Jin.

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The author Zengbian Chen declares that he/she has no conflict of interest; the author Jie Jin declares that he/she has no conflict of interest; the author Qi Lu declares that he/she has no conflict of interest.

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Chen, Z., Jin, J. & Lu, Q. STAMP2 alleviates microglial neurotoxicity by inhibiting LPS-induced NF-κB activation. Mol. Cell. Toxicol. 20, 335–342 (2024). https://doi.org/10.1007/s13273-023-00346-1

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  • DOI: https://doi.org/10.1007/s13273-023-00346-1

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