Purpose: 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 and materials: 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.