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

Research output: Contribution to journalArticlepeer-review

144 Scopus citations

Abstract

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
Volume104
Issue number2
DOIs
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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