Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury

Stephanos Kyrkanides, Amy H. Moore, John A. Olschowka, Jo Anna C. Daeschner, Jacqueline P. Williams, John T. Hansen, OáBanion Kerry O’Banion

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146 Scopus citations


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.

Original languageEnglish
Pages (from-to)159-169
Number of pages11
JournalMolecular Brain Research
Issue number2
StatePublished - 2002

Bibliographical note

Funding Information:
This work was supported by grants from the NIH (NS33553 and P01 CA11051).

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience


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