title: Calcitriol downregulates TNF-α and IL-6 expression in cultured placental cells from preeclamptic women.
abstract: 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 pro-inflammatory 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-α, IFN-γ, IL-6 and IL-1β in cultured placental cells from preeclamptic women by using qPCR and ELISA. Placentas were collected after cesarean section from preeclamptic women and enriched trophoblastic preparations were cultured in the absence or presence of different calcitriol concentrations during 24h. In these cell cultures, pro-inflammatory cytokines TNF-α and IL-6 secretion and mRNA expression were downregulated by calcitriol (P<0.05). No significant effects of calcitriol upon IFN-γ and IL-1β were observed. In addition, basal expression of TNF-α, IL-6 and IL-1β 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.
authors.affiliation: Departamento de Biología de la Reproducción Carlos Gual Castro, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, Tlalpan 14000, México, D.F., Mexico.
authors.forename: Nancy
authors.initials: N
authors.lastname: Noyola-Martínez
authors.forename: Lorenza
authors.initials: L
authors.lastname: Díaz
authors.forename: Euclides
authors.initials: E
authors.lastname: Avila
authors.forename: Ali
authors.initials: A
authors.lastname: Halhali
authors.forename: Fernando
authors.initials: F
authors.lastname: Larrea
authors.forename: David
authors.initials: D
authors.lastname: Barrera
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015726:Giant Cells / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism; D015850:Interleukin-6 / Q000096:biosynthesis / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D002117:Calcitriol