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Attenuation of cerebral ischemic injury in interferon regulatory factor 3‐deficient rat
Author(s) -
Li Lei,
Qin JuanJuan,
Guo Sen,
Zhang Peng,
Gong Jun,
Zhang XiaoJing,
Zheng Ankang,
Xia Hao,
Li Hongliang
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13448
Subject(s) - irf1 , knockout mouse , interferon regulatory factors , genetically modified mouse , apoptosis , ischemia , transcription factor , stroke (engine) , biology , inflammation , endogeny , neuroscience , medicine , oxidative stress , endocrinology , immune system , innate immune system , transgene , immunology , receptor , gene , biochemistry , mechanical engineering , engineering
Interferon regulatory factor 3 ( IRF 3) is a transcription factor that plays a central role in the innate immune response, apoptosis, and oncogenesis. Previous studies have shown that endogenous IRF 3 does not affect stroke in mice; however, paradoxically, elevated IRF 3 expression was observed in the rat brains following cerebral ischemia/reperfusion (I/R) injury, indicating that IRF 3 may have different functions during stroke in rats than in mice. A clear and comprehensive study of the effect of IRF 3 on stroke in rats has been hampered by the lack of an IRF 3‐knockout rat strain. In this study, a novel IRF 3 knockout rat strain and a transgenic rat strain with neuronal‐specific IRF 3 over‐expression ( IRF 3‐ TG ) were created. Subsequently, the generated IRF 3‐knockout rats, the neuronal‐specific IRF 3 over‐expressing rats and their corresponding controls were subjected to transient middle cerebral artery occlusion and followed by reperfusion, to investigate the exact role of IRF 3 in cerebral I/R in rats. In contrast to the results in mice, IRF 3 deficiency in rats provided significant protection against cerebral I/R injury and inhibited neuronal apoptosis, inflammation, and oxidative stress after cerebral I/R injury; the opposite patterns were observed in neuronal‐specific IRF 3 over‐expressing rats. Taken together, these data demonstrate that IRF 3 plays a negative regulatory role in cerebral I/R in rats, and IRF 3 may be an attractive therapeutic target for preventing stroke.In the present study, we discovered that the transcription factor IRF3, which plays a central role in the innate immune response, apoptosis, and oncogenesis, could exacerbate cerebral ischemia/reperfusion (I/R) injury via activating caspase‐dependent neuronal apoptosis, inducing inflammation and oxidative stress. These findings suggest that IRF3 may be an attractive therapeutic target for the prevention of stroke.