Vol. 292, Issue 3, 1032-1041, March 2000

Polarized Distribution of Interleukin-1 Receptors and Their Role in Regulation of Serotonin Transporter in Placenta¹

Ramesh Kekuda, Frederick H. Leibach, Todd C. Furesz, Carl H. Smith and Vadivel Ganapathy

Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia (R.K., F.H.L., V.G.) and Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri (T.C.F., C.H.S.)

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-1 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-1, indicating involvement of tyrosine phosphorylation in the process. Treatment of JAR cells with IL-1 activates mitogen-activated protein kinases and nuclear factor-B. The nuclear factor-B that is responsive to IL-1 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 ¹²⁵I-IL-1 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.