期刊
AMERICAN JOURNAL OF PATHOLOGY
卷 186, 期 8, 页码 1982-1988出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.ajpath.2016.04.002
关键词
-
类别
资金
- Japan Society for the Promotion of Science (JSPS) [KAKENHI 26460338, 15K08230]
- [820140600019]
- Grants-in-Aid for Scientific Research [15K08230, 14J05605] Funding Source: KAKEN
Microglial cells play a key role in neuronal damage in neurodegenerative disorders. Overactivated microglia induce detrimental neurotoxic effects through the excess production of proinflammatory cytokines. However, the mechanisms of microglial activation are poorly understood. We focused on prostaglandin E-2 type 4 receptor-associated protein (EPRAP), which suppresses macrophage activation. We demonstrated that EPRAP exists in microglia in the brain. Furthermore, EPRAP-deficient mice displayed less microglial accumulation, and intraperitoneal administration of Lipopolysaccharide (LPS) Led to reduced expression of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 mRNA in the brains of EPRAP-deficient mice. Consistently, EPRAP-deficient microglia showed a marked decrease in the production of tumor necrosis factor-alpha and monocyte chemoattractant protein-1 induced by LPS treatment compared with wild-type controls. In addition, EPRAP deficiency decreased microglial activation and neuronal cell death induced by intraventricular injection of kainic acid. EPRAP deficiency impaired the LPS-induced phosphorylation of c-jun N-terminal kinase and p38 mitogen-activated protein kinase in microglia. The phosphorylation levels of mitogen-activated protein kinase kinase 4 which phosphorylates c-jun N-terminal kinase and p38 mitogen-activated protein kinase were also decreased in EPRAP-deficient microglia after LPS stimulation. Although EPRAP in macrophages plays a role in the attenuation of inflammation, EPRAP promotes proinflammatory activation of microglia through mitogen-activated protein kinase kinase 4-mediated signaling and may be key to the deteriorating neuronal damage brought on by brain inflammation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据