Regulation of prostaglandin E2 synthesis after brain irradiation.
OBJECTIVE
A local tissue reaction, termed neuroinflammation, occurs after irradiation of brain tissue. Previous work suggested that cyclooxygenase (COX)-2 activity was important for changes in gene expression associated with neuroinflammation as well as increased prostaglandin E2 (PGE2) levels seen after radiation treatment.


METHODS
To begin to determine the contributions of other enzymes involved in PGE2 production, we examined protein levels of COX-1 and COX-2 as well as 2 PGE synthases (membrane and cytosolic PGES) 4 h after 35 Gy single dose irradiation to the brains of C3HeN mice. We also evaluated the effects of specific COX inhibitors on PGE2 production and PGES expression.


RESULTS
As expected, COX-2 expression increased after radiation exposure. Brain irradiation also increased tissue protein levels for both PGES isoforms. Specific COX-2 inhibition with NS398 lowered brain PGE2 levels by about 60%. Surprisingly, COX-1 inhibition with SC560 completely prevented the elevation of PGE2 seen after irradiation. Interestingly, NS398 reduced the membrane-associated PGES isoform, whereas SC560 treatment lowered cytosolic isoform levels below those seen in unirradiated controls.


CONCLUSIONS
Taken together, these data indicate that both cyclooxygenases contribute to PGE2 production in irradiated brain and reveal dependence of PGES isoforms expression on specific cyclooxygenase activities.
Moore
Amy H
AH
Department of Neurobiology and Anatomy, University of Rochester School of Medicine and Dentistry, Rochester, NY 14642, USA.
Olschowka
John A
JA
Williams
Jacqueline P
JP
Okunieff
Paul
P
O'Banion
M Kerry
MK
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000528:radiation effects*; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis*; D004660:Encephalitis / Q000209:etiology / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011833:Radiation Injuries, Experimental / Q000378:metabolism*
D008565:Membrane Proteins; D012333:RNA, Messenger; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone