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Dexamethasone sodium phosphate attenuates lipopolysaccharide-induced neuroinflammation in microglia BV2 cells

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Abstract

Abnormal neuroinflammation ignited by overproduction of chemokines and cytokines via microglial cells can induce the occurrence and development of neurodegenerative disorders. The aim of this study is to investigate the effects of dexamethasone sodium phosphate (Dex-SP) on chemokine and cytokine secretion in lipopolysaccharide (LPS)-activated microglial cells. LPS markedly enhanced the secretion of pro-inflammatory factors such as regulated on activation, normal T cell expressed and secreted (RANTES), transforming growth factor beta-β1 (TGF-β1) and nitric oxide (NO), but decreased the production of macrophage inflammatory protein-1α (MIP-1α) and interleukin 10 (IL-10) in BV-2 microglial cells. Furthermore, LPS increased BV-2 microglial cell migration. However, Dex-SP treatment had the opposite effect, dampening the secretion of RANTES, TGF-β1, and NO, while increasing the production of MIP-1α and IL-10 and blocking migration of LPS-stimulated BV-2 microglial cells. Furthermore, Dex-SP markedly suppressed the LPS-induced degradation of IRAK-1 and IRAK-4, and blocked the activation in TRAF6, p-TAK1, and p-JNK in BV-2 microglial cells. These results showed that Dex-SP inhibited the neuroinflammatory response and migration in LPS-activated BV-2 microglia by inhibiting the secretion of RANTES, TGF-β1, and NO and increasing the production of MIP-1α and IL-10. The molecular mechanism of Dex-SP may be associated with inhibition of TRAF6/TAK-1/JNK signaling pathways mediated by IRAK-1 and IRAK-4.

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Funding

This study was supported by the Foundation of Shanghai University of Medicine & Health Sciences (Talent Introduction Project 2018).

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Authors and Affiliations

  1. College of Pharmacy, Shanghai University of Medical & Health Sciences, Shanghai, China

    Bin Hui

  2. Health School attached to Shanghai University of Medical & Health Sciences, Shanghai, China

    Bin Hui

  3. Jiyuan Shi People’s Hospital, Jiyuan, Henan, China

    Xin Yao

  4. Department of Emergency Medicine, Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University, Shanghai, China

    Liping Zhang

  5. College of Medicine, Jiaxing University, Jiaxing, China

    Qinhua Zhou

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  1. Bin Hui
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  2. Xin Yao
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  3. Liping Zhang
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  4. Qinhua Zhou
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Contributions

Bin Hui, Liping Zhang, and Qinhua Zhou designed the experiments; Bin Hui, Xin Yao, Qinhua Zhou, and Liping Zhang performed parts of the experiments; Bin Hui, Qinhua Zhou, and Liping Zhang analyzed the data; Bin Hui, Qinhua Zhou, and Liping Zhang wrote the manuscript.

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Correspondence to Liping Zhang or Qinhua Zhou.

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Hui, B., Yao, X., Zhang, L. et al. Dexamethasone sodium phosphate attenuates lipopolysaccharide-induced neuroinflammation in microglia BV2 cells. Naunyn-Schmiedeberg's Arch Pharmacol 393, 1761–1768 (2020). https://doi.org/10.1007/s00210-019-01775-3

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