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‐1β) is an inflammatory cytokine whose expression is elevated in brain during seizures, ischemia, and injury. Expression of IL‐1β 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‐1β in rat primary hippocampal cultures. As assessed by reverse transcriptase/polymerase chain reaction (RT/PCR), recombinant mouse IL‐1β (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‐1β treatment, and 2‐hour treatment with the PAF analog mcPAF mimicked the effects of IL‐1β on COX‐2 mRNA levels. Following injury, synaptic plasticity changes may be affected by IL‐1β‐PAF‐COX‐2 neuronal signaling. J. Neurosci. Res. 58:593–598, 1999. © 1999 Wiley‐Liss, Inc.