Interleukin-1 beta-induced expression of the prostaglandin E2-receptor subtype EP3 in U373 astrocytoma cells depends on protein kinase C and nuclear factor-kappaB

Both interleukin-1 beta (IL-1 beta) and prostaglandins (PGs) are important mediators of physiological and pathophysiological processes in the brain. PGE(2) exerts its effects by binding to four different types of PGE(2) receptors named EP1-EP4. EP3 has found to be expressed in neurons, whereas expression of EP3 in glial cells has not been reported in the brain yet. Here we describe IL-1 beta-induced EP3 receptor expression in human astrocytoma cells, primary astrocytes of rat and human origin and in rat brain. Using western blot, we found a marked up-regulation of EP3 receptor synthesis in human and rat primary glial cells. Intracerebroventricular administration of IL-1 beta stimulated EP3 receptor synthesis in rat hippocampus. The analysis of involved signal transduction pathways by pathway-specific inhibitors revealed an essential role of protein kinase C and nuclear factor-kappa B in astrocytic IL-1 beta-induced EP3 synthesis. Our data suggest that PGE(2) signaling in the brain may be altered after IL-1 beta release due to up-regulation of EP3 receptors. This might play an important role in acute and chronic conditions such as cerebral ischemia, traumatic brain injury, HIV-encephalitis, Alzheimer's disease and prion diseases in which a marked up-regulation of IL-1 beta is followed by a prolonged increase of PGE(2) levels in the brain.