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

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.

• Authors: Mei Jiang, Xinghui Liu, Denghai Zhang, Ying Wang, Xiaoxia Hu, Fengxia Xu, Mingming Jin, Fanfan Cao, Limin Xu
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 15 Issue 1 Pg. 78 (Mar 14 2018) ISSN: 1742-2094 [Electronic] England
• PMID: 29540209 (Publication Type: Journal Article)

Chemical References

• IL1RL1 protein, human
• IL3 protein, human
• Interleukin-1 Receptor-Like 1 Protein
• Interleukin-3
• Neuroprotective Agents
• Pentacyclic Triterpenes
• Triterpenes
• celastrol

Topics

• Aged
• Animals
• Apoptosis (drug effects)
• Brain Infarction (drug therapy, etiology)
• Brain Injuries (drug therapy, etiology)
• Brain Ischemia (complications)
• Cell Polarity (drug effects)
• Coculture Techniques
• Disease Models, Animal
• Female
• Humans
• Interleukin-1 Receptor-Like 1 Protein (genetics, metabolism)
• Interleukin-3 (metabolism)
• Macrophages (drug effects)
• Male
• Microglia (drug effects)
• Middle Aged
• Neuroprotective Agents (pharmacology, therapeutic use)
• Pentacyclic Triterpenes
• Rats
• Rats, Sprague-Dawley
• Recovery of Function (drug effects)
• Sensory Gating (drug effects)
• Stroke (complications, etiology)
• Triterpenes (therapeutic use)