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Peripheral Blood Monocyte Tolerance Alleviates Intraperitoneal Lipopolysaccharides-Induced Neuroinflammation in Rats Via Upregulating the CD200R Expression

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Abstract

Neuroinflammation is an important pathogenesis of Parkinson’s disease (PD). The peripheral immune system could produce profound effects on central immunities. The peripheral blood monocyte (PBM) immune tolerance is the refractoriness of immune system to avoid overactive peripheral inflammation. The PBM are also actively involved in central immune activities. There is evidence implying the probable failure of immune tolerance and impairment of CD200/CD200R signaling in PD patients. Here we aimed to explore the effects of PBM tolerance in peripheral LPS-induced neuroinflammation as well as the specific roles of CD200/CD200R pathway in PBM tolerance. We found that repeated intraperitoneal administration of 0.3 mg/kg LPS was able to induce the PBM tolerance. PBM tolerance reduced peripheral LPS-induced elevation of serum TNF-α, IL-1β expression and TLR4 expression in PBM. PBM tolerance and PBM depletion alleviated peripheral LPS-induced neuroinflammation demonstrated by reduced proinflammatory cytokines in brain and blocked microglia activation. The CD200R expression in PBM was upregulated in PBM tolerance group after intraperitoneal administration of high-dose LPS in vivo and the blockade of CD200/CD200R interaction induced the failure of PBM tolerance in vitro. These results suggested the PBM tolerance could attenuate the peripheral LPS-induced neuroinflammation via upregulating the CD200R expression and the CD200/CD200R signaling played a key role in PBM tolerance. Effective regulation of the PBM in periphery may be a potential way to limit neuroinflammation while the CD200R on PBM could be used as a potential therapeutic target to alleviate neuroinflammation.

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Abbreviations

PD:

Parkinson’s disease

PBM:

Peripheral blood monocyte

LPS:

Lipopolysaccharides

SN:

Substantia nigra

ROS:

Reactive oxygen species

CNS:

Central nervous system

BBB:

Blood brain barrier

TNF-α:

Tumor necrosis factor-α

IL-1β:

Interleukin-1β

TH:

Tyrosine hydroxylase

McAb:

Monoclonal antibody

PcAb:

Polyclonal antibody

ANOVA:

Analysis of variance

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Acknowledgements

This work was supported by the National Natural Science Foundation of China [No. 81371421].

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang, 110001, Liaoning, People’s Republic of China

    Liping Xia, Xin Xie, Yang Liu & Xiaoguang Luo

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  1. Liping Xia
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  2. Xin Xie
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Correspondence to Xiaoguang Luo.

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Xia, L., Xie, X., Liu, Y. et al. Peripheral Blood Monocyte Tolerance Alleviates Intraperitoneal Lipopolysaccharides-Induced Neuroinflammation in Rats Via Upregulating the CD200R Expression. Neurochem Res 42, 3019–3032 (2017). https://doi.org/10.1007/s11064-017-2334-5

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  • DOI: https://doi.org/10.1007/s11064-017-2334-5

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