TY - JOUR T1 - Polarized Distribution of Interleukin-1 Receptors and Their Role in Regulation of Serotonin Transporter in Placenta JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 1032 LP - 1041 VL - 292 IS - 3 AU - Ramesh Kekuda AU - Frederick H. Leibach AU - Todd C. Furesz AU - Carl H. Smith AU - Vadivel Ganapathy Y1 - 2000/03/01 UR - http://jpet.aspetjournals.org/content/292/3/1032.abstract N2 - 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. The American Society for Pharmacology and Experimental Therapeutics ER -