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Arsenic Activates the NLRP3 Inflammasome and Disturbs the Th1/Th2/Th17/Treg Balance in the Hippocampus in Mice

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Abstract

Arsenic exerts neurotoxicity and immunomodulatory effects. Studies have shown that the nervous system is not considered to be an immune-privileged site. However, the effect of arsenic-induced neuroimmune toxicity has rarely been reported. We aimed to investigate the toxic effects of arsenic on the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome and the Th1/Th2/Th17/Treg balance in the brain tissue of mice. Mice were exposed to NaAsO2 (0, 2.5, 5, and 10 mg/kg) for 24 h. Our results showed that 10 mg/kg arsenic exposure significantly decreased brain and hippocampal indices (p < 0.05). The mRNA and protein levels of the blood‒brain barrier (BBB) tight junction protein occludin were decreased in the 5 and 10 mg/kg arsenic-treated groups. Compared with those in the control group, NLRP3 protein levels in 10 mg/kg arsenic-treated mice, caspase-1 protein levels in 2.5, 5, and 10 mg/kg arsenic-treated mice, and IL-1β protein levels in 5 and 10 mg/kg arsenic-treated mice were increased in the hippocampus (p < 0.05). In addition, arsenic induced a hippocampal inflammatory response by upregulating the mRNA levels of the proinflammatory factors IL-6 and TNF-α and downregulating the mRNA level of the anti-inflammatory factor IL-10. Moreover, arsenic decreased the mRNA levels of the Th1 and Th2 transcription factors T-bet and GATA3 and the cytokines IFN-γ and IL-4 and increased the mRNA levels of the Th17 transcription factor RORγt and the cytokine IL-22 (p < 0.05). Collectively, our study demonstrated that arsenic could induce immune-inflammatory responses by regulating the NLRP3 inflammasome and CD4+ T lymphocyte differentiation. These results provide a novel strategy to block the arsenic-induced impairment of neuroimmune responses.

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Data Availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (NSFC) (no. 81803180 and no. 81803200), the Basic Research Project of Liaoning Provincial Department of Education Youth Project (no. LJKQZ2021173), Shenyang Middleyounger Scientific and Technological Innovation Support Plan (no. RC190479 and no. RC200238), Liaoning Province Key Research and Development Program Guidance Plan (no. 2019JH8/10300047), Shenyang Science and Technology Plan Project Social Governance Science and Technology Special Project (no. 21–108-9–11), and Science and Technology Innovation Fund of Shenyang Medical College (no. Y20210513).

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  1. Hui Jing and Nan Yan contributed equally.

Authors and Affiliations

  1. Department of Toxicology, School of Public Health, Shenyang Medical College, Shenyang, 110034, China

    Hui Jing, Zhou Li, Qian Wang, Kangjie Xu & Xiaoxu Duan

  2. Department of Medical Applied Technology, Shenyang Medical College, Shenyang, 110034, China

    Nan Yan

  3. Department of Health Inspection, College of Public Health, Shenyang Medical College, Shenyang, 110034, China

    Ronghua Fan

  4. Clinical Medicine (“5+3” integrated Training), The First Affiliated Hospital of China Medical University, Shenyang, 110001, China

    Xinkang Hu

  5. Department of Maternal, Child and Adolescent Health, School of Public Health, Shenyang Medical College, Shenyang, 110034, China

    Lifeng Zhang

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Contributions

Conceptualization, funding acquisition, data curation, formal analysis, visualization, and writing—original draft, H.J.; software, data curation, and validation, R.H.F.; formal analysis and software, N.Y.; investigation, Z.L.; methodology, Q.W., K.J.X., X.K.H.; resources, validation, writing—review, supervision and editing, L.F.Z.; funding acquisition, writing—review and editing, supervision, project administration, X.X.D.

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Correspondence to Lifeng Zhang or Xiaoxu Duan.

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Animal use has been approved by the Animal Use and Care Committee at Shenyang Medical College (protocol number: SYYXY2020031201).

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Jing, H., Yan, N., Fan, R. et al. Arsenic Activates the NLRP3 Inflammasome and Disturbs the Th1/Th2/Th17/Treg Balance in the Hippocampus in Mice. Biol Trace Elem Res 201, 3395–3403 (2023). https://doi.org/10.1007/s12011-022-03421-1

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