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
✍ Scribed by Michael J. Serou; Mark A. DeCoster; Nicolas G. Bazan
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 67 KB
- Volume
- 58
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Interleukin-1 beta (IL-1
) is an inflammatory cytokine whose expression is elevated in brain during seizures, ischemia, and injury. Expression of IL-1 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-1 in rat primary hippocampal cultures. As assessed by reverse transcriptase/polymerase chain reaction (RT/PCR), recombinant mouse IL-1 (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 posttreatment. 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-1 treatment, and 2-hour treatment with the PAF analog mcPAF mimicked the effects of IL-1 on COX-2 mRNA levels. Following injury, synaptic plasticity changes may be affected by IL-1-PAF-COX-2 neuronal signaling.