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J Neuroinflammation. 2018 Mar 14;15(1):78. doi: 10.1186/s12974-018-1124-6.

Celastrol treatment protects against acute ischemic stroke-induced brain injury by promoting an IL-33/ST2 axis-mediated microglia/macrophage M2 polarization.

Author information

1
Department of neurology, Shanghai Gongli Hospital, The Second Military Medical University, Shanghai, 200135, People's Republic of China.
2
Department of Clinical Laboratory, Shanghai Gongli Hospital, The Second Military Medical University, 207 Ju Ye Road, Pudong New Area, Shanghai, 200135, People's Republic of China.
3
Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, The Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, People's Republic of China.
4
Department of Clinical Laboratory, Shanghai Gongli Hospital, The Second Military Medical University, 207 Ju Ye Road, Pudong New Area, Shanghai, 200135, People's Republic of China. asdjinmingming@126.com.
5
Sino-French Cooperative Central Lab, Shanghai Gongli Hospital, The Second Military Medical University, 207 Ju Ye Road, Pudong New District, Shanghai, 200135, People's Republic of China. yffs.c@163.com.
6
Department of Clinical Laboratory, Shanghai Gongli Hospital, The Second Military Medical University, 207 Ju Ye Road, Pudong New Area, Shanghai, 200135, People's Republic of China. 13564378807@163.com.

Abstract

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)-1β, IL-6, and tumor necrosis factor (TNF)-α) 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.

KEYWORDS:

Acute ischemic stroke; Celastrol; IL-33; M2 microglia/macrophage polarization; ST2

PMID:
29540209
PMCID:
PMC5853059
DOI:
10.1186/s12974-018-1124-6
[Indexed for MEDLINE]
Free PMC Article

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