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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Astrocytes / drug effects
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Astrocytes / enzymology*
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Astrocytes / radiation effects
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Brain / drug effects
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Brain / enzymology*
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Brain / radiation effects
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Cell Culture Techniques
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Chemokine CCL2 / genetics
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Chemokine CXCL2
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Chemokines / genetics
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Cyclooxygenase 2
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Cytokines / genetics
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Dinoprostone / genetics
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Encephalitis / enzymology*
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Encephalitis / genetics*
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Encephalitis / physiopathology
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Gene Expression Regulation, Enzymologic / drug effects
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Gene Expression Regulation, Enzymologic / genetics*
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Gene Expression Regulation, Enzymologic / radiation effects
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Intercellular Adhesion Molecule-1 / genetics
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Isoenzymes / antagonists & inhibitors
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Isoenzymes / metabolism*
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Isoenzymes / radiation effects
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Male
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Matrix Metalloproteinase 9 / genetics
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Mice
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Mice, Inbred C3H
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Microglia / drug effects
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Microglia / enzymology*
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Microglia / radiation effects
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Nitric Oxide Synthase / genetics
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Nitrobenzenes / pharmacology
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Prostaglandin-Endoperoxide Synthases / metabolism*
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Prostaglandin-Endoperoxide Synthases / radiation effects
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism
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RNA, Messenger / radiation effects
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Sulfonamides / pharmacology
Substances
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Chemokine CCL2
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Chemokine CXCL2
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Chemokines
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Cxcl2 protein, mouse
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Cytokines
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Isoenzymes
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Nitrobenzenes
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RNA, Messenger
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Sulfonamides
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N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide
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Intercellular Adhesion Molecule-1
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Nitric Oxide Synthase
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Cyclooxygenase 2
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Prostaglandin-Endoperoxide Synthases
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Matrix Metalloproteinase 9
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Dinoprostone