Glycyrrhizin protects against focal cerebral ischemia via inhibition of T cell activity and HMGB1-mediated mechanisms.
In: Journal of Neuroinflammation, Jg. 13 (2016-09-08), S. 1-12
Online
academicJournal
Zugriff:
Background: Glycyrrhizin (Gly) protects against brain injury induced by stroke. We studied whether Gly achieves its protection by inhibiting T cell activity and high-mobility group box 1 (HMGB1) release in the ischemic brain. Methods: Stroke was induced by transient middle cerebral artery occlusion in rats and mice. Gly was injected intraperitoneally before or after stroke. We measured infarction, neuroinflammatory cells, gene expressions of interferon-γ (IFNγ), IL-4, and IL-10 in CD4 T cells, HMGB1 release, and T cell proliferation in cultured splenocytes. Results: Gly treatment reduced infarctions and neuroinflammation characterized by the infiltration of CD68-positive macrophages and myeloperoxidase-positive neutrophils, which corresponds to a reduction in the number of T cells and their subsets, CD4 and CD8 T cells, in the ischemic brain, as measured by flow cytometry. Unlike in wild-type animals, Gly did not offer protection in nude rats and severe combined immunodeficient (SCID) mice who had no T cells, while Gly reduced infarction in both nude rats and SCID mice whose T cells were reconstituted, suggesting that T cells should be the target of Gly. In addition, Gly administration inhibited T cell proliferation stimulated by ConA in in vitro assays and inhibited HMGB1 release from the ischemic brain. Furthermore, Gly attenuated gene expression of IFNγ, but not IL-4 and IL-10 in CD4 T cells. Lastly, HMGB1 promoted T cell proliferation stimulated by ConA, which was inhibited by the addition of Gly. Conclusions: Gly blocks infarction by inhibiting IFNγ-mediated T cell activity, which is at least partly modulated by HMGB1 activity. [ABSTRACT FROM AUTHOR]
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Glycyrrhizin protects against focal cerebral ischemia via inhibition of T cell activity and HMGB1-mediated mechanisms.
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Autor/in / Beteiligte Person: | Xiong, Xiaoxing ; Gu, Lijuan ; Wang, Yan ; Luo, Ying ; Zhang, Hongfei ; Lee, Jessica ; Krams, Sheri ; Zhu, Shengmei ; Zhao, Heng |
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Zeitschrift: | Journal of Neuroinflammation, Jg. 13 (2016-09-08), S. 1-12 |
Veröffentlichung: | 2016 |
Medientyp: | academicJournal |
ISSN: | 1742-2094 (print) |
DOI: | 10.1186/s12974-016-0705-5 |
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