Interleukin-22 Plays a Protective Role by Regulating the JAK2-STAT3 Pathway to Improve Inflammation, Oxidative Stress, and Neuronal Apoptosis following Cerebral Ischemia-Reperfusion Injury.
Yong-Fei DongChengyun HuChunxia HuangJie GaoWanxiang NiuDi WangYang WangChao-Shi NiuPublished in: Mediators of inflammation (2021)
The interleukins (ILs) are a pluripotent cytokine family that have been reported to regulate ischemic stroke and cerebral ischemia/reperfusion (I/R) injury. IL-22 is a member of the IL-10 superfamily and plays important roles in tissue injury and repair. However, the effects of IL-22 on ischemic stroke and cerebral I/R injury remain unclear. In the current study, we provided direct evidence that IL-22 treatment decreased infarct size, neurological deficits, and brain water content in mice subjected to cerebral I/R injury. IL-22 treatment remarkably reduced the expression of inflammatory cytokines, including IL-1β, monocyte chemotactic protein- (MCP-) 1, and tumor necrosis factor- (TNF-) α, both in serum and the ischemic cerebral cortex. In addition, IL-22 treatment also decreased oxidative stress and neuronal apoptosis in mice after cerebral I/R injury. Moreover, IL-22 treatment significantly increased Janus tyrosine kinase (JAK) 2 and signal transducer and activator of transcription (STAT) 3 phosphorylation levels in mice and PC12 cells, and STAT3 knockdown abolished the IL-22-mediated neuroprotective function. These findings suggest that IL-22 might be exploited as a potential therapeutic agent for ischemic stroke and cerebral I/R injury.
Keyphrases
- oxidative stress
- cerebral ischemia
- subarachnoid hemorrhage
- ischemia reperfusion injury
- tyrosine kinase
- atrial fibrillation
- cell death
- cell proliferation
- heart failure
- transcription factor
- endothelial cells
- multiple sclerosis
- endoplasmic reticulum stress
- immune response
- dendritic cells
- heat shock
- white matter
- cerebral blood flow
- induced apoptosis
- signaling pathway
- diabetic rats
- heat shock protein
- protein kinase