期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 90, 期 11, 页码 2127-2133出版社
WILEY-BLACKWELL
DOI: 10.1002/jnr.23105
关键词
chemokine; microglia; neuron-glia interaction; organotypic slice culture
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan [19045001, 2126001]
- Japan Society for the Promotion of Science [20790052]
- Japan Health Sciences Foundation
- Grants-in-Aid for Scientific Research [20790052, 19045001, 23680053] Funding Source: KAKEN
Chemokines are potent chemoattractants for immune and hematopoietic cells. In the central nervous system, chemokines play an important role in inflammatory responses through activation of infiltrating leukocytes and/or resident glial cells. We previously demonstrated that N-methyl-D-aspartate (NMDA)-evoked neuronal injury induced astrocytic production of monocyte chemoattractant protein-1 (MCP-1, CCL2) via sustained activation of extracellular signal-regulated kinase (ERK) in rat organotypic slice cultures. In the present study, we examined mRNA expression and protein production of macrophage inflammatory protein-1a (MIP-1a, CCL3) induced by NMDA-evoked neuronal injury in the slice cultures. MIP-1a mRNA expression was transiently increased by NMDA treatment in a concentration-dependent manner. Double-fluorescence immunohistochemistry revealed that MIP-1a was produced predominantly in microglia. Depletion of microglial cells from the slice cultures by pretreatment with liposome-encapsulated clodronate abrogated the increase in MIP-1a mRNA expression after NMDA treatment. NMDA-induced MIP-1a mRNA expression was partially but significantly inhibited by the c-Jun N-terminal kinase inhibitor SP600125; conversely, the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 enhanced it. U0126, a MAP kinase/ERK kinase inhibitor, did not affect mRNA expression. These results, combined with our previous findings, demonstrate that NMDA-evoked neuronal injury differentially induces MIP-1a and MCP-1 production in microglia and astrocytes, respectively, through activation of different intracellular signaling pathways. (c) 2012 Wiley Periodicals, Inc.
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