Calcitriol downregulates TNF-α and IL-6 expression in cultured placental cells from preeclamptic women

Placenta is an important source and target of hormones that contribute to immunological tolerance and maintenance of pregnancy. In preeclampsia (PE), placental calcitriol synthesis is low; whereas proinflammatory cytokines levels are increased, threatening pregnancy outcome. Previously, we showed that calcitriol inhibits Th-1 cytokines under experimental inflammatory conditions in normal trophoblasts. However, a study of the regulation of inflammatory cytokines by calcitriol in trophoblasts from a natural inflammatory condition, such as PE, is still lacking. Therefore, the aim of the present study was to investigate calcitriol effects upon TNF-alpha, IFN-gamma, IL-6 and IL-1 beta in cultured placental cells from pre-eclamptic women by using qPCR and ELISA. Placentas were collected after cesarean section from pre-eclamptic women and enriched trophoblastic preparations were cultured in the absence or presence of different calcitriol concentrations during 24 h. In these cell cultures, pro-inflammatory cytokines TNF-alpha and IL-6 secretion and mRNA expression were downregulated by calcitriol (P < 0.05). No significant effects of calcitriol upon IFN-gamma and IL-1 beta were observed. In addition, basal expression of TNF-alpha, IL-6 and IL-1 beta decreased as the cells formed syncytia. Our study supports an important autocrine/paracrine role of placental calcitriol in controlling adverse immunological responses at the feto-maternal interface, particularly in gestational pathologies associated with exacerbated inflammatory responses such as preeclampsia. (C) 2012 Elsevier Ltd. All rights reserved.