期刊
JOURNAL OF NEUROINFLAMMATION
卷 15, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/s12974-018-1124-6
关键词
Celastrol; ST2; IL-33; M2 microglia/macrophage polarization; Acute ischemic stroke
资金
- Foundation of Discipline Leader in Health Systems of the Pudong New District [PWRd2014-02, PWRd2014-09]
- Shanghai Sailing Program [15YF1410800]
- National Natural Science Foundation of China [81400793, 81201029]
- Science and Technology Development Fund of Pudong New District Minsheng Scientific Research (Medical and Health) Project [PKJ2017-Y24]
- Shanghai Pudong District Science and Technology Innovation Project [PKJ2013-Y03]
- Shanghai Health and Family Planning Commission General Program [201540395]
- Key Specialty Construction Project of Shanghai Municipal Commission of Health and Family Planning [ZK2015B16]
- Shanghai Traditional Chinese Medicine Content Construction Innovation Project [ZY3-CCCX-3-7001]
Background: Acute ischemic stroke (AIS) is the most common type of cerebrovascular disease and is a leading cause of disability and death worldwide. Recently, a study suggested that transformation of microglia from the pro-inflammatory M1 state to the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. Celastrol, a traditional oriental medicine, may have anti-inflammatory and neuroprotective effects. However, the underlying mechanisms remain unknown. Methods: We first determined the expression levels of inflammatory factors in patients and rodent models associated with AIS; we then determined the anti-inflammatory effects of celastrol in AIS, both in vivo and in vitro, using animal models of middle cerebral artery occlusion (MCAO) and cell models of oxygen-glucose deprivation (OGD) treatment with or without celastrol, respectively. Results: The results indicated that expression of both inflammatory (interleukin (IL)-1 beta, IL-6, and tumor necrosis factor (TNF)-alpha) cytokines, as well as the anti-inflammatory cytokine, IL-33, and IL-10, were increased following AIS in patients and in animal models. Furthermore, in vitro experiments confirmed that celastrol treatment decreased inflammatory cytokine expression induced by OGD through an IL-33/ST2 axis-mediated M2 microglia/macrophage polarization. Finally, celastrol is protected against ischemic-induced nerve injury, both in vivo and in vitro. Conclusions: Taken together, these data suggest that celastrol post-treatment reduces ischemic stroke-induced brain damage, suggesting celastrol may represent a novel potent pharmacological therapy.
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