Interleukin-6 stimulates placental lactogen expression by human trophoblast cells.
Interleukin-6 (IL-6) stimulates the release of hCG from syncytiotrophoblast cells, but the effects of IL-6 and other cytokines on the release of placental lactogen (hPL) are unknown. To determine the effect of IL-6 on hPL release, we exposed an enriched fraction of trophoblast cells (prepared by the isopycnic centrifugation of enzymatically dispersed term placenta) continuously to IL-6 (500 U/ml) for up to 6 days. The amounts of hPL released by the IL-6-exposed cells during days 3 and 6 were 177.6 +/- 2.4% and 267.5 +/- 12.6% that of control cells, respectively (P < 0.0001 in each instance). In addition, the hPL messenger RNA (mRNA) contents of the IL-6-exposed cells after 3 and 6 days of exposure were 2.2- and 4.7-fold that of control cells. The stimulatory effect of IL-6 on hPL release and hPL mRNA levels was dose dependent, with a minimal effective dose of 50 U/ml. IL-1 beta, which is known to stimulate IL-6 production by human trophoblast cells, also stimulated dose-dependent increases in hPL release and hPL mRNA levels. IL-6 (500 U/ml) had no effect on trophoblast differentiation, but stimulated a 20-fold increase in hPL promoter activity in BeWo choriocarcinoma cells transfected transiently with a plasmid containing 2.3 kilobases of the hPL promoter coupled to the chloramphenicol acetyltransferase gene. In addition, BeWo cells exposed to IL-6 (500 U/ml) for 3 and 6 days contained 2.4- and 3.2-fold more hPL mRNA levels than control cells. Because placental macrophages and syncytiotrophoblast cells release IL-6, these results strongly suggest an autocrine/paracrine role for IL-6 in the regulation of hPL release. The increase in hPL release appears to be due at least in part to an increase in hPL gene expression.
Division of Endocrinology, Children's Hospital Medical Center, Cincinnati, Ohio 45229-4744.
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Stephanou
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Handwerger
D002454:Cell Differentiation; D002822:Choriocarcinoma; D006063:Chorionic Gonadotropin / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000494:pharmacology*; D010928:Placental Lactogen / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection; D014327:Trophoblasts / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014594:Uterine Neoplasms
D006063:Chorionic Gonadotropin; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D010928:Placental Lactogen