Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury
Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury
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DOI：
10.1016/s0169-328x(02)00353-4
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发表时间：
2002-08-15
期刊：
影响因子：
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通讯作者：
O'Banion, MK
中科院分区：
文献类型：
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作者：
Kyrkanides, S;Moore, AH;O'Banion, MK
虽然环氧化酶-2（考克斯-2）在外周炎症中的作用已被充分证实，但其在脑炎症中的作用却知之甚少。为此，我们研究了考克斯-2表达在小鼠脑电离辐射后，在体内，以及在小鼠胶质细胞培养物在体外。利用考克斯-2选择性抑制剂NS-398检测考克斯-2在调节脑炎症中的可能作用。我们的研究结果表明，考克斯-2显着诱导星形胶质细胞和小胶质细胞培养的辐射损伤，以及在大脑中。NS-398降低了照射脑中前列腺素E-2水平的升高。此外，NS-398给药显著减弱了所检查的大多数炎症介质的诱导水平，包括TNF α、IL-1 β、IL-6、iNOS、ICAM-1和MMP-9。相反，趋化因子MIP-2和MCP-1在NS-398给药后显示出增强的诱导水平。这些结果表明，考克斯-2调节放射损伤后脑中的炎症反应，并建议使用考克斯-2选择性抑制剂来管理CNS炎症。(C)2002 Elsevier Science B. V.保留所有权利。
Although the contribution of cyclooxygenase-2 (COX-2) to peripheral inflammation is well documented, little is known about its role in brain inflammation. For this purpose we studied COX-2 expression in the mouse brain following ionizing radiation in vivo, as well as in murine glial cell cultures in vitro. The possible role of COX-2 in modulating brain inflammation was examined utilizing NS-398, a COX-2 selective inhibitor. Our results indicate that COX-2 is significantly induced in astrocyte and microglial cultures by radiation injury as well as in brain. Increased levels of prostaglandin E-2 in irradiated brain were reduced by NS-398. Moreover, NS-398 administration significantly attenuated levels of induction for the majority of inflammatory mediators examined, including TNFalpha, IL-1beta, IL-6, iNOS, ICAM-1, and MMP-9. In contrast, the chemokines MIP-2 and MCP-1 showed enhanced levels of induction following NS-398 administration. These results indicate that COX-2 modulates the inflammatory response in brain following radiation injury, and suggest the use of COX-2 selective inhibitors for the management of CNS inflammation. (C) 2002 Elsevier Science B.V. All rights reserved.