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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Histamine upregulates the expression of histamine receptors and increases the neuroprotective effect of astrocytes

Authors: Jiawen Xu, Xiang Zhang, Qingqing Qian, Yiwei Wang, Hongquan Dong, Nana Li, Yanning Qian, Wenjie Jin

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Astrocytes have attracted increasing attention over recent decades for their role in neuroinflammation. Histamine, a major aminergic brain neurotransmitter, has an important influence on the main activities of astrocytes, such as ion homeostasis, energy metabolism, and neurotransmitter clearance. However, little is known about the impact of histamine on astrocyte immunomodulatory function.

Methods

The expression of all known histamine receptor subtypes was examined in primary astrocytes. Then, primary astrocytes were pretreated with selective histamine receptor antagonists and stimulated with histamine. Cellular activation, proinflammatory cytokine production, and expression of neurotrophic factors were assessed.

Results

Astrocytes could constitutively express three histamine receptors (H1R, H2R, and H3R), and these three histamine receptors could be selectively upregulated to varying degrees upon histamine treatment. Histamine also dose-dependently stimulated astrocyte activation and subsequent production of glial cell-derived neurotrophic factor (GDNF), whereas it suppressed the secretion of the proinflammatory factors tumor necrosis factor-alpha (TNF-α) and interleukin-1β (IL-1β). The effects of histamine were completely abolished by either an H1R or H3R antagonist, while an H2R antagonist attenuated the effects partly.

Conclusions

The present study identified the expression of H1R, H2R, and H3R on astrocytes. We also demonstrated that negative regulation of astrocytic TNF-α and IL-1β production and the enhancement of astrocytic GDNF stimulated by histamine were receptor-mediated processes in which all three of the expressed histamine receptors (H1R, H2R, and H3R) were involved. These findings may further clarify the involvement and mechanism of astrocyte activation in neuroinflammation.
Appendix
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Metadata
Title
Histamine upregulates the expression of histamine receptors and increases the neuroprotective effect of astrocytes
Authors
Jiawen Xu
Xiang Zhang
Qingqing Qian
Yiwei Wang
Hongquan Dong
Nana Li
Yanning Qian
Wenjie Jin
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1068-x

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