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Research ArticleCELLULAR AND MOLECULAR

Polarized Distribution of Interleukin-1 Receptors and Their Role in Regulation of Serotonin Transporter in Placenta

Ramesh Kekuda, Frederick H. Leibach, Todd C. Furesz, Carl H. Smith and Vadivel Ganapathy
Journal of Pharmacology and Experimental Therapeutics March 2000, 292 (3) 1032-1041;
Ramesh Kekuda
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Frederick H. Leibach
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Todd C. Furesz
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Carl H. Smith
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Vadivel Ganapathy
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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

  • 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

  • ↵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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Journal of Pharmacology and Experimental Therapeutics: 292 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 292, Issue 3
1 Mar 2000
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Research ArticleCELLULAR AND MOLECULAR

Polarized Distribution of Interleukin-1 Receptors and Their Role in Regulation of Serotonin Transporter in Placenta

Ramesh Kekuda, Frederick H. Leibach, Todd C. Furesz, Carl H. Smith and Vadivel Ganapathy
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1032-1041;

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Research ArticleCELLULAR AND MOLECULAR

Polarized Distribution of Interleukin-1 Receptors and Their Role in Regulation of Serotonin Transporter in Placenta

Ramesh Kekuda, Frederick H. Leibach, Todd C. Furesz, Carl H. Smith and Vadivel Ganapathy
Journal of Pharmacology and Experimental Therapeutics March 1, 2000, 292 (3) 1032-1041;
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