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Interleukin-35 from Interleukin-4-Stimulated Macrophages Alleviates Oxygen Glucose Deprivation/Re-oxygenation-Induced Neuronal Cell Death via the Wnt/β-Catenin Signaling Pathway

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Abstract

Currently, brain stroke is one of the leading causes of death and disabilities. It results in depletion of oxygen and glucose in certain areas of the brain, leading to neuronal death. Re-oxygenation has been proven to attenuate neuronal damage; however, sudden oxygen supply may also cause oxidative stress and subsequent inflammation. Hence, therapies to suppress re-oxygenation-induced oxidative damage are urgently needed. Interleukin (IL)-35, an immunomodulator secreted by regulatory T cells and regulatory B cells, is proven to be a strong immune-repressive cytokine. Here, we investigated the potential role of IL-35 in a disease model of oxygen glucose deprivation/re-oxygenation (OGD/R) and found that M2 macrophage-derived IL-35 significantly alleviated inflammatory response induced by oxidative stress. Our results also showed that IL-35 treatment decreased OGD/R-induced neuronal cell death and inflammatory response. Additionally, we demonstrated that IL-35 suppresses inflammatory response via the Wnt/β-catenin signaling pathway. Hence, our findings indicate that IL-35 therapy has great potential in the treatment of OGD/R-induced oxidative damage and related inflammatory diseases.

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All data generated or analyzed during this study are included in this published article and its additional files.

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Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital, Hengyang Medical School, University of South China, Hengyang, China

    Tao Xiao, Hongtao Qu, Zhiqing Zeng & Chuanghua Li

  2. Department of Neurology, The First Affiliated Hospital, Hengyang Medical School, University of South China, No. 69 Chuanshan Road, Hengyang, Hunan Province, China

    Juan Wan

Authors
  1. Tao Xiao
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  2. Hongtao Qu
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  3. Zhiqing Zeng
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  4. Chuanghua Li
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  5. Juan Wan
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Contributions

Tao Xiao and Juan Wan conceived and designed the study. Tao Xiao, Hongtao Qu, and Zhiqing Zeng collected the data. Chuanghua Li analyzed the data. Tao Xiao wrote the manuscript. All authors read and approved the final manuscript for publication.

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Correspondence to Juan Wan.

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Xiao, T., Qu, H., Zeng, Z. et al. Interleukin-35 from Interleukin-4-Stimulated Macrophages Alleviates Oxygen Glucose Deprivation/Re-oxygenation-Induced Neuronal Cell Death via the Wnt/β-Catenin Signaling Pathway. Neurotox Res 40, 420–431 (2022). https://doi.org/10.1007/s12640-022-00478-7

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  • DOI: https://doi.org/10.1007/s12640-022-00478-7

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