Polarized distribution of interleukin-1 receptors and their role in regulation of serotonin transporter in placenta.
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-1beta 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-1beta, indicating involvement of tyrosine phosphorylation in the process. Treatment of JAR cells with IL-1beta activates mitogen-activated protein kinases and nuclear factor-kappaB. The nuclear factor-kappaB that is responsive to IL-1beta 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 for (125)I-IL-1beta 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.
Kekuda
R
R
Department of Biochemistry, Medical College of Georgia, Augusta, Georgia, USA.
Leibach
F H
FH
Furesz
T C
TC
Smith
C H
CH
Ganapathy
V
V
D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins; D010920:Placenta / Q000378:metabolism*; D011247:Pregnancy; D017472:Receptors, Interleukin-1 / Q000032:analysis / Q000502:physiology*; D050486:Serotonin Plasma Membrane Transport Proteins; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D017472:Receptors, Interleukin-1; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D020929:Mitogen-Activated Protein Kinase Kinases