TY - JOUR
T1 - Cyclooxygenase-2 modulates brain inflammation-related gene expression in central nervous system radiation injury
AU - Kyrkanides, Stephanos
AU - Moore, Amy H.
AU - Olschowka, John A.
AU - Daeschner, Jo Anna C.
AU - Williams, Jacqueline P.
AU - Hansen, John T.
AU - Kerry O’Banion, OáBanion
N1 - Funding Information:
This work was supported by grants from the NIH (NS33553 and P01 CA11051).
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
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U2 - 10.1016/S0169-328X(02)00353-4
DO - 10.1016/S0169-328X(02)00353-4
M3 - Article
C2 - 12225870
AN - SCOPUS:0142229824
SN - 0169-328X
VL - 104
SP - 159
EP - 169
JO - Molecular Brain Research
JF - Molecular Brain Research
IS - 2
ER -