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

Abstract

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‐1 β , 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.