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.
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.
Waschbisch
Anne
A
Department of Psychiatry, University of Freiburg Medical School, Freiburg, Germany.
Fiebich
Bernd L
BL
Akundi
Ravi Shankar
RS
Schmitz
M Lienhard
ML
Hoozemans
Jeroen J M
JJ
Candelario-Jalil
Eduardo
E
Virtainen
Nina
N
Veerhuis
Robert
R
Slawik
Helen
H
Yrjänheikki
Juha
J
Hüll
Michael
M
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001254:Astrocytoma / Q000378:metabolism*; D015152:Blotting, Northern / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018078:Receptors, Prostaglandin E / Q000235:genetics / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D004791:Enzyme Inhibitors; D007375:Interleukin-1; D016328:NF-kappa B; C545647:PTGER3 protein, human; C545649:Ptger3 protein, rat; D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D011493:Protein Kinase C