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Sodium P-aminosalicylic Acid Inhibits Manganese-Induced Neuroinflammation in BV2 Microglial Cells via NLRP3-CASP1 Inflammasome Pathway

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Abstract

Background

Sodium p-aminosalicylic acid (PAS-Na) was reported to exhibit anti-inflammatory effect in the nervous system. However, the mechanism by which PAS-Na exhibits anti-inflammatory effects on manganese (Mn)-stimulated BV2 microglia cells remains unclear. Thus, this study investigated the role of PAS-Na in Mn-stimulated BV2 microglial cells.

Methods

Microglia-like BV2 were treated with MnCl2 with or without the non-steroidal anti-inflammatory drug PAS-Na for 12 or 24 h to examine cell viability using MTT; for 24 or 48 h to examine levels of NLRP3, CASP1, IL-1β, and IL-18 mRNA using Real-Time quantitative PCR; for 48 h to examine levels of NLRP3 and CASP1 inflammasomes, measured by western blot analysis; and for 48 h to examine levels of inflammatory cytokines, measured by enzyme-linked immunosorbent assay.

Results

The MTT assay showed that PAS-Na produced significant neuroprotective effect by preventing Mn-induced inflammation in BV2 microglial cells. PAS-Na significantly concentration and time dependently inhibited Mn-induced production of NLRP3, CASP1, IL-1β, and IL-18.

Conclusion

Taken together, our results suggest that PAS-Na exerts anti-inflammatory effects in Mn-stimulated BV2 microglial cells via downregulation of NLRP3, CASP1, IL-1β, and I L-18. Furthermore, a high concentration and prolonged PAS-Na treatment appear necessary for its therapeutic efficacy. Taken together, we conclude that PAS-Na affords therapeutic efficacy in mitigating neurological conditions associated with neuroinflammation.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

Mn:

manganese

PD:

Parkinson’s disease

AD:

Alzheimer’s disease

CNS:

central nervous system

IL1β:

interleukin 1 β

IL18:

interleukin 18

NLRP3:

NLR family, pyrin domain containing 3

CASP1:

caspase-1

PAS-Na:

sodium p-aminosalicylic acid

qPCR:

quantitative real-time polymerase chain reaction

ELISA:

enzyme-linked immunosorbent assay

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Acknowledgments

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.

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Author notes

  1. Yuanyuan Fang, Dongjie Peng and Yuan Liang contributed equally to this work.

Authors and Affiliations

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

    Yuanyuan Fang, Dongjie Peng, Yuan Liang, Lili Lu, Junyan Li, Lin Zhao, Shiyan Ou, Shaojun Li & Yueming Jiang

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

    Yuanyuan Fang, Dongjie Peng, Yuan Liang, Lili Lu, Junyan Li, Lin Zhao, Shiyan Ou, Shaojun Li & Yueming Jiang

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

    Michael Aschner

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Contributions

YF, DP, and YL carried out the studies and drafted the manuscript. LL and SO assisted with the establishment of the cell model. JL, LZ, and MA performed the statistical analysis. YF, DP, YL, LL, SO, JL, and LZ took part in the sample preparation and experimental analysis. YJ and MA designed the study. YJ led the study. All authors read and approved the final manuscript.

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Correspondence to Yueming Jiang.

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Fang, Y., Peng, D., Liang, Y. et al. Sodium P-aminosalicylic Acid Inhibits Manganese-Induced Neuroinflammation in BV2 Microglial Cells via NLRP3-CASP1 Inflammasome Pathway. Biol Trace Elem Res 199, 3423–3432 (2021). https://doi.org/10.1007/s12011-020-02471-7

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