期刊
MOLECULAR BRAIN RESEARCH
卷 104, 期 2, 页码 159-169出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/S0169-328X(02)00353-4
关键词
brain inflammation; glia; irradiation; prostaglandins; nonsteroidal; anti-inflammatory drug
资金
- NCI NIH HHS [P01 CA11051] Funding Source: Medline
- NINDS NIH HHS [NS33553] Funding Source: Medline
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.
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