title: Interferon regulatory factor 8 protects against cerebral ischaemic-reperfusion injury.
abstract: Interferon regulatory factor 8 (IRF8), a transcriptional regulator in the IRF family, has been implicated in innate immunity, immune cell differentiation and tumour cell apoptosis. In the present study, we found that IRF8 is constitutively expressed in the brain and suppressed after cerebral ischaemia in a time-dependent manner. IRF8 knockout (IRF8-KO) mice, wild type (WT) mice, neuron-specific IRF8 transgenic (TG) mice and non-transgenic mice were used in a transient cerebral ischaemic model. The IRF8 knockout mice exhibited aggravated apoptosis, inflammation and oxidative injury in the ischaemic brain, eventually leading to poorer stroke outcomes, whereas neuron-specific IRF8 transgenic mice showed a marked inhibition of apoptosis and improved stroke outcomes. To model ischaemia/reperfusion conditions in vitro, primary cortical neurons were cultured and subjected to transient oxygen and glucose deprivation for 60 min. Similar to the in vivo study, IRF8 knockdown by Ad-shIRF8 resulted in increased apoptosis, whereas IRF8 over-expression by Ad-IRF8 significantly decreased neuronal apoptosis. These data indicate that IRF8 is strongly protective in ischaemic stroke by regulating neuronal apoptosis, the inflammatory response and oxidative stress. In the present study, we found that the transcriptional factor IRF8 plays a protective role in the cerebral ischaemic-reperfusion injury by attenuating neuronal apoptosis, oxidative stress and inflammation. Besides the known function of IRF8 in regulating the inflammatory gene expression, we first demonstrated that IRF8 can directly modulate apoptosis and oxidative stress by controlling the relative genes expression.
authors: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China; Cardiovascular Research Institute of Wuhan University, Wuhan, China.
authors: Mei
authors: M
authors: Xiang
authors: Lang
authors: L
authors: Wang
authors: Sen
authors: S
authors: Guo
authors: Yan-Yun
authors: YY
authors: Lu
authors: Hao
authors: H
authors: Lei
authors: Ding-Sheng
authors: DS
authors: Jiang
authors: Yan
authors: Y
authors: Zhang
authors: Yi
authors: Y
authors: Liu
authors: Yan
authors: Y
authors: Zhou
authors: Xiao-Dong
authors: XD
authors: Zhang
authors: Hongliang
authors: H
authors: Li
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D002545:Brain Ischemia / Q000517:prevention & control*; D002478:Cells, Cultured; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control; D005452:Fluoresceins; D005455:Fluorescent Antibody Technique; D005456:Fluorescent Dyes; D005822:Genetic Vectors; D020287:In Situ Nick-End Labeling; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000502:physiology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D051379:Mice; D018345:Mice, Knockout; D009422:Nervous System Diseases / Q000503:physiopathology; D009474:Neurons / Q000473:pathology / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D016133:Polymerase Chain Reaction; D051381:Rats; D015427:Reperfusion Injury / Q000517:prevention & control*; D020521:Stroke / Q000503:physiopathology; D000099185:Interferon Regulatory Factor-8
chemical_list: D005452:Fluoresceins; D005456:Fluorescent Dyes; D050835:Interferon Regulatory Factors; D007770:L-Lactate Dehydrogenase; D000099185:Interferon Regulatory Factor-8; C435731:fluoro jade
keywords: IRF8; apoptosis; inflammation; ischaemia; oxidative stress; stroke