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Sodium P-aminosalicylic Acid Attenuates Manganese-Induced Neuroinflammation in BV2 Microglia by Modulating NF-κB Pathway

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Abstract

Exposure to high levels of manganese (Mn) leads to brain Mn accumulation, and a disease referred to as manganism. Activation of microglia plays an important role in Mn-induced neuroinflammation. Sodium p-aminosalicylic acid (PAS-Na) is a non-steroidal anti-inflammatory drug that inhibits Mn-induced neuroinflammation. The aim of the current study was to explore the role of NF-κB in the protective mechanism of PAS-Na on Mn-induced neuroinflammation in BV2 microglial experimental model. We treated BV2 microglia with 200 μM Mn for 24 h followed by 48 h treatment with graded concentrations of PAS-Na, using an NF-kB inhibitor, JSH-23, as a positive control. MTT results established that 200 and 400 μM PAS-Na treatment increased the Mn-induced cell viability reduction. NF-κB (P65) mRNA expression and the phosphorylation of p65 were increased in Mn-treated BV2 cell, and suppressed by PAS-Na, analogous to the effect of JSH-23 pretreatment. Furthermore, PAS-Na significantly reduced the contents of the inflammatory cytokine TNF-α and IL-1β, both of which were increased by Mn treatment. The current results show that PAS-Na attenuated Mn-induced inflammation by abrogating the activation of the NF-κB signaling pathways and reduced the release of pro-inflammatory cytokines.

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Data Availability

The datasets used and/or analyzed during the current research are available from the corresponding author on request.

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Funding

Thanks to the fund support provided by grants from the National Natural Science Foundation of China (NSFC 81460505, 81973094). MA was supported in part by a grant from the National Institute of Environmental Health Science (NIEHS) R01ES10563 and R01ES07331.

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Author notes

  1. Junyan Li, Yue Deng and Dongjie Peng contributed equally to this work.

Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Guangxi Medical University, Shuang-yong Road No.22, Nanning, 530021, Guangxi, China

    Junyan Li, Yue Deng, Dongjie Peng, Lin Zhao, Yuanyuan Fang, Xiaojuan Zhu, Shaojun Li, Shiyan Ou & Yueming Jiang

  2. Guangxi Colleges and Universities Key Laboratory of Prevention and Control of Highly Prevalent Diseases, Guangxi Medical University, Nanning, China

    Junyan Li, Yue Deng, Dongjie Peng, Lin Zhao, Yuanyuan Fang, Xiaojuan Zhu, Shaojun Li, Shiyan Ou & Yueming Jiang

  3. Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA

    Michael Aschner

Authors
  1. Junyan Li
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  2. Yue Deng
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  3. Dongjie Peng
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  4. Lin Zhao
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  5. Yuanyuan Fang
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  6. Xiaojuan Zhu
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  7. Shaojun Li
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  8. Michael Aschner
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  9. Shiyan Ou
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  10. Yueming Jiang
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Correspondence to Yueming Jiang.

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Li, J., Deng, Y., Peng, D. et al. Sodium P-aminosalicylic Acid Attenuates Manganese-Induced Neuroinflammation in BV2 Microglia by Modulating NF-κB Pathway. Biol Trace Elem Res 199, 4688–4699 (2021). https://doi.org/10.1007/s12011-021-02581-w

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