Abstract
We investigated the expression of interleukin-1 (IL-1) receptors and their involvement in the regulation of the serotonin transporter gene expression in human placenta. IL-1β is an activator of the serotonin transporter gene expression in JAR human placental choriocarcinoma cells as demonstrated by an increase in the steady-state levels of the transporter mRNA and in serotonin transport activity. This activation is blocked by IL-1 receptor antagonist. Genistein also blocks the effect of IL-1β, indicating involvement of tyrosine phosphorylation in the process. Treatment of JAR cells with IL-1β activates mitogen-activated protein kinases and nuclear factor-κB. The nuclear factor-κB that is responsive to IL-1β in these cells is the p65 homodimer. Northern blot analysis and reverse transcription-polymerase chain reaction revealed that JAR cells and human placenta express type I and type II IL-1 receptors. The binding sites for125I-IL-1β are localized predominantly in the maternal-facing brush border membrane of the syncytiotrophoblast. These results show that IL-1 in the maternal circulation is likely to play a critical role in the regulation of the serotonin transporter gene expression in the placenta.
Footnotes
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Send reprint requests to: Vadivel Ganapathy, Ph.D., Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, GA 30912-2100. E-mail:vganapat{at}mail.mcg.edu
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↵1 This study was supported by National Institutes of Health Grant DA 10045.
- Abbreviations:
- SERT
- serotonin transporter
- IL-1
- interleukin-1
- MAP
- mitogen-activated protein
- NF-κB
- nuclear factor-κB
- PMSF
- phenylmethylsulfonyl fluoride
- ERK
- extracellular signal-regulated kinase
- EMSA
- electrophoretic mobility shift assay
- RT-PCR
- reverse transcription-polymerase chain reaction
- bp
- base pair
- Received July 14, 1999.
- Accepted November 19, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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