Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury.
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.
Kyrkanides
Stephanos
S
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Moore
Amy H
AH
Olschowka
John A
JA
Daeschner
JoAnna C
JC
Williams
Jacqueline P
JP
Hansen
John T
JT
Kerry O'Banion
M
M
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D018929:Cell Culture Techniques; D018932:Chemokine CCL2 / Q000235:genetics; D054426:Chemokine CXCL2; D018925:Chemokines / Q000235:genetics; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000235:genetics; D015232:Dinoprostone / Q000235:genetics; D004660:Encephalitis / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D051379:Mice; D008809:Mice, Inbred C3H; D017628:Microglia / Q000187:drug effects / Q000201:enzymology* / Q000528:radiation effects; D019001:Nitric Oxide Synthase / Q000235:genetics; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism* / Q000528:radiation effects; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D013449:Sulfonamides / Q000494:pharmacology
D018932:Chemokine CCL2; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D016207:Cytokines; D007527:Isoenzymes; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D018799:Intercellular Adhesion Molecule-1; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D020780:Matrix Metalloproteinase 9; D015232:Dinoprostone