Interleukin-1 beta activates expression of cyclooxygenase-2 and inducible nitric oxide synthase in primary hippocampal neuronal culture: platelet-activating factor as a preferential mediator of cyclooxygenase-2 expression.
Interleukin-1 beta (IL-1beta) is an inflammatory cytokine whose expression is elevated in brain during seizures, ischemia, and injury. Expression of IL-1beta and its receptor can also be observed in normal brain. Platelet-activating factor (PAF) is also a dual mediator that promotes neuronal plasticity responses as well as inflammation. We have determined the role of PAF in the regulation of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) genes by IL-1beta in rat primary hippocampal cultures. As assessed by reverse transcriptase/polymerase chain reaction (RT/PCR), recombinant mouse IL-1beta (1 nM) led to an induction of COX-2 mRNA which peaked at 2 hours, declined to baseline levels by 4 hours, began to rise again by 6 hours, and remained elevated at 24 hours post-treatment. iNOS mRNA was also induced, but unlike COX-2, its abundance peaked at 4 hours and decreased by 6 hours to a plateau lasting through 24 hours. Pretreatment with PAF antagonist BN50730 blocked induction of COX-2 mRNA by 2-hour IL-1beta treatment, and 2-hour treatment with the PAF analog mcPAF mimicked the effects of IL-1beta on COX-2 mRNA levels. Following injury, synaptic plasticity changes may be affected by IL-1beta-PAF-COX-2 neuronal signaling.
Serou
M J
MJ
LSU Health Sciences Center, Neuroscience Center, New Orleans, LA 70112, USA.
DeCoster
M A
MA
Bazan
N G
NG
D000818:Animals; D001381:Azepines / Q000494:pharmacology; D051546:Cyclooxygenase 2; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D007375:Interleukin-1 / Q000502:physiology*; D007527:Isoenzymes / Q000096:biosynthesis*; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000494:pharmacology*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis*; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D058924:Thienopyridines; D014230:Triazoles / Q000494:pharmacology
D001381:Azepines; D007375:Interleukin-1; D007527:Isoenzymes; D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors; D011994:Recombinant Proteins; D058924:Thienopyridines; D014230:Triazoles; C066686:BN 50730; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases