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

Abstract

Both interleukin-1beta (IL-1beta) and prostaglandins (PGs) are important mediators of physiological and pathophysiological processes in the brain. PGE2 exerts its effects by binding to four different types of PGE2 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-1beta-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-1beta 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-kappaB in astrocytic IL-1beta-induced EP3 synthesis. Our data suggest that PGE2 signaling in the brain may be altered after IL-1beta 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-1beta is followed by a prolonged increase of PGE2 levels in the brain.

• Authors: Anne Waschbisch, Bernd L Fiebich, Ravi Shankar Akundi, M Lienhard Schmitz, Jeroen J M Hoozemans, Eduardo Candelario-Jalil, Nina Virtainen, Robert Veerhuis, Helen Slawik, Juha Yrjänheikki, Michael Hüll
• Journal: Journal of neurochemistry (J Neurochem) Vol. 96 Issue 3 Pg. 680-93 (Feb 2006) ISSN: 0022-3042 [Print] England
• PMID: 16405508 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enzyme Inhibitors
• Interleukin-1
• NF-kappa B
• PTGER3 protein, human
• Ptger3 protein, rat
• RNA, Messenger
• Receptors, Prostaglandin E
• Receptors, Prostaglandin E, EP3 Subtype
• Protein Kinase C

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Astrocytoma (metabolism)
• Blotting, Northern (methods)
• Blotting, Western (methods)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Drug Interactions
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Interleukin-1 (pharmacology)
• Male
• NF-kappa B (physiology)
• Protein Kinase C (physiology)
• RNA, Messenger (biosynthesis)
• Rats
• Rats, Wistar
• Receptors, Prostaglandin E (genetics, metabolism)
• Receptors, Prostaglandin E, EP3 Subtype
• Reverse Transcriptase Polymerase Chain Reaction (methods)
• Time Factors