Calcitriol inhibits TNF-α-induced inflammatory cytokines in human trophoblasts

Abstract Elevated placental proinflammatory cytokine release is associated with miscarriage, preterm labor and preeclampsia. Specifically, tumor necrosis factor-α (TNF-α)-induced cytokines may threaten pregnancy outcome. Since trophoblasts produce calcitriol, a hormone with strong immunosuppressive properties, we assessed the effects of this secosteroid on inflammatory cytokines induced in trophoblasts by challenge with TNF-α. The effects of calcitriol on synthesis of mRNAs encoding interleukin-6 (IL-6), interferon-γ (IFN-γ), and TNF-α were measured by real time RT-PCR. Secreted cytokines were quantified by ELISA. The effects of TNF-α on CYP24A1, chorionic gonadotropin (hCG), 3β-hydroxysteroid dehydrogenase (HSD3B1) and P 450 -aromatase (CYP19) mRNA expression were also studied. TNF-α stimulated IL-6, IFN-γ and its own expression more than 3-fold over controls ( P P