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Dopamine Alters Lipopolysaccharide-Induced Nitric Oxide Production in Microglial Cells via Activation of D1-Like Receptors

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Abstract

Dopamine (DA) is important in the maintenance of normal nervous system function. DA is the target of multiple drugs, and it induces critical alterations in immune cells. However, these impacts are controversial, and the mechanism remains unclear. In the present study, we treated BV-2 microglial cells and primary microglia with DA and measured the changes in cytokines. We also identified the expression of DA receptors (DRs) using confocal and immunofluorescent microscopy. Specific agonists and antagonists of D1-like DRs (D1DR and D5DR) were used to observe alterations in cytokines. Western blot and siRNA interference were performed to investigate the involvement of the downstream signaling molecules of DRs. We also measured changes in mitogen-activated protein kinases (MAPKs) and the nuclear factor-kappa B (NF-κB) signaling pathway and assessed their involvement using inhibitors. We found that DA alone produced no effects on IL-6, TNF-α or nitric oxide (NO) production, and it inhibited lipopolysaccharide (LPS)-induced NO in microglial cells. Microglia expressed a high abundance of D1-like DRs (D1DR and D5DR). The agonists inhibited NO production, and antagonists reversed the DA-induced suppression of NO. Adenylatec cyclase (AC), cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) mediated DA function, and cAMP-response element binding protein (CREB) was not involved. ERK1/2 and NF-κB, but not p-38 or JNK, played roles in DA-suppressed NO generation via altering inducible nitric oxide synthase (iNOS) transcription. These data illustrate that DA modulates LPS-induced NO production via the AC/cAMP-PKA-ERK1/2-NF-κB-iNOS axis in mouse microglia, and D1-like DRs are involved. The present study provides functional evidence for an essential role of DA in immunoregulation.

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Data Availability

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

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Acknowledgements

The authors thank Drs. Wu Feng and Ren Huixun in the Department of Immunology and Pathogenic Biology of Xi’an Jiaotong University for the great help in the modification of the manuscript.

Funding

This work was supported by the National Natural Science Foundation of China (Grant Numbers: 81273196, 81430048, 81772034).

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Authors and Affiliations

  1. Department of Immunology and Pathogenic Biology, College of Basic Medicine, Xi’an Jiaotong University Health Science Center, Xi’an, 710061, China

    Biao Wang, Guodong Li, Yuwei Jia, Jing Wang & Yanjiong Chen

  2. Key Laboratory of the Health Ministry for Forensic Medicine, Forensic Medicine College of Xi’an Jiaotong University, Xi’an, 710061, China

    Teng Chen

  3. Department of Laboratory, The Second Affiliated Hospital of Medical College of Xi’an Jiaotong University, Xi’an, 710004, China

    Li Xue

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  1. Biao Wang
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Wang, B., Chen, T., Li, G. et al. Dopamine Alters Lipopolysaccharide-Induced Nitric Oxide Production in Microglial Cells via Activation of D1-Like Receptors. Neurochem Res 44, 947–958 (2019). https://doi.org/10.1007/s11064-019-02730-7

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