标题：TIPE2, a novel regulator of immunity, protects against experimental stroke
作者机构：[Zhang, Y] Dept. of Pharmacology, Shandong University School of Medicine, 44 West Wenhua Rd., Jinan, Shandong 250012, China;[ Wei, X] Dept. of Pharmac 更多
通讯作者地址：[Yi, F]Shandong Univ, Sch Med, Dept Pharmacol, 44 W Wenhua Rd, Jinan 250012, Shandong, Peoples R China.
来源：The Journal of biological chemistry
摘要：The inflammatory responses accompanying stroke are recognized to contribute to secondary ischemic injury. TIPE2 is a very recently identified negative regulator of inflammation that maintains immune homeostasis. However, it is unknown whether TIPE2 is expressed in the brain and contributes to the regulation of cerebral diseases. In this study, we explored the potential roles of TIPE2 in cerebral ischemia/reperfusion injury. TIPE2-/- mice were used to assess whether TIPE2 provides neuroprotection following cerebral ischemia/reperfusion induced by middle cerebral artery occlusion (MCAO), and in vitro primary cerebral cell cultures were used to investigate the expression and regulation of TIPE2. Our results show that genetic ablation of the Tipe2 gene significantly increased the cerebral volume of infarction and neurological dysfunction in mice subjected to MCAO. Flow cytometric analysis revealed more infiltrating macrophages, neutrophils, and lymphocytes in the ischemic hemisphere of TIPE2-/- mice. The responses to inflammatory cytokines and chemokines were significantly increased in TIPE2-/- mouse brain after MCAO. We further observed that TIPE2 was highly induced in WT mice after cerebral ischemia and was expressed mainly in microglia/macrophages, but not in neurons and astrocytes. Finally, we found that regulation of TIPE2 expression was associated with NADPH oxidase activity. These findings demonstrate, for the first time, that TIPE2 is involved in the pathogenesis of stroke and suggest that TIPE2 plays an essential role in a signal transduction pathway that links the inflammatory immune response to specific conditions after cerebral ischemia. Targeting TIPE2 may be a new therapeutic strategy for stroke treatment.