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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.

Background and Purpose. Abdominal aortic aneurysm (AAA) is a chronic inflammatory disorder and the important causes of death among men over the age of 65 years. Interleukin-12p35 (IL12p35) is an inflammatory cytokine that participates in a variety of inflammatory diseases. However, the role of IL12p35 in the formation and development of AAA is still unknown. Experimental Approach. Male apolipoprotein E-deficient (Apoe-/-) mice were generated and infused with 1.44 mg/kg angiotensin II (Ang II) per day. We found that IL12p35 expression was noticeably increased in the murine AAA aorta and isolated aortic smooth muscle cells (SMCs) after Ang II stimulation. IL12p35 silencing promoted Ang II-induced AAA formation and rupture in Apoe-/- mice. IL12p35 silencing markedly increased the expression of inflammatory cytokines, including IL-1β, IL-6, and tumor necrosis factor-α (TNF-α), in both the serum and AAA aorta. Additionally, IL12p35 silencing exacerbated SMC apoptosis in Apoe-/- mice after Ang II infusion. IL12p35 silencing significantly increased signal transducer and activator of transcription (STAT) 4 phosphorylation levels in AAA mice, and STAT4 knockdown abolished the IL12p35-mediated proinflammatory response and SMC apoptosis. Interpretation. Silencing IL12p35 promotes AAA formation by activating the STAT4 pathway, and IL12p35 may serve as a novel and promising therapeutic target for AAA treatment.