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Molecular & Cellular Toxicology

, Volume 15, Issue 2, pp 173–183 | Cite as

Manganese induces neuroinflammation via NF-κB/ROS NLRP3 pathway in rat brain striatum and HAPI cells

  • Xinyuan Zhao
  • Lifeng Yin
  • Yifan Wu
  • Muxi Han
  • Yin Zhuang
  • Yewen Cong
  • Yiming Liu
  • Gang Chen
  • Junkang JiangEmail author
Original Paper
  • 15 Downloads

Abstract

Backgrounds

Chronic exposure to excessive Mn can result in neurodegenerative symptoms, whose precise molecular mechanism remains largely unclear. Here, we measured the role and mechanism of NLRP3 in Mninduced neuroinflammation in vivo and vitro.

Methods

The effects of Mn on NLRP3 activation were investigated by Westernblot, IHC, immunofluorescence analysis, as well as ELISA. We assessed NF-κB activation through measurement of phosphorylation and nuclear translocation. The mechanisms bywhich Mn induced NLRP3 activation were assessed by specific inhibitors.

Results

We found that Mn exposure facilitated the activation of NLRP3 inflammasome to promote the production of IL-1β and IL-18 in dose- and time-dependent manners in HAPI cells. In addition, the NLRP3 inflammasome was also dramatically activated in microglia of rat brain striatum after Mn exposure. We also found increased ROS and NF-κB activation. Notably, the activation of NLRP3 was significantly attenuated by pretreatment with NF-κB and ROS inhibitors.

Conclusion

These findings suggest that NLRP3 activation plays an important role in Mn-induced neuroinflammation, and it is associated with NF-κB and ROS.

Keywords

Manganese Microglia NLRP3 inflammasome NF-κB/ROS Neuroinflammation 

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Copyright information

© The Korean Society of Toxicogenomics and Toxicoproteomics and Springer Nature B.V. 2019

Authors and Affiliations

  • Xinyuan Zhao
    • 1
  • Lifeng Yin
    • 1
  • Yifan Wu
    • 1
  • Muxi Han
    • 1
  • Yin Zhuang
    • 1
  • Yewen Cong
    • 1
  • Yiming Liu
    • 1
  • Gang Chen
    • 1
  • Junkang Jiang
    • 1
    Email author
  1. 1.Department of Occupational Medicine and Environmental Toxicology, School of Public HealthNantong UniversityNantong, JiangsuPeople’s Republic of China

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