title: Calcitriol inhibits interleukin-10 expression in cultured human trophoblasts under normal and inflammatory conditions.
abstract: Preeclampsia is associated with systemic inflammation and increased expression of placental Th1-cytokines. IL-10 and calcitriol inhibit proinflammatory cytokines expression in human placenta helping to fetal allograft toleration. Regulation of placental IL-10 by calcitriol and Th-1 cytokines has not yet been fully elucidated. Since it is believed that calcitriol promotes a shift from a Th1- to a Th2 profile, we hypothesized that it would stimulate IL-10 in a normal and an inflammatory scenario to conjointly restrain inflammation. Therefore, we investigated calcitriol effects upon IL-10 expression in cultured human trophoblasts obtained from normal (NT) and preeclamptic (PE) pregnancies. Similar studies in the presence of TNF-α (as an inflammatory stressor) were also performed. Calcitriol dose-dependently inhibited IL-10 expression in NT, PE and TNF-α-challenged trophoblasts (P<0.05). This effect was prevented by a vitamin D receptor (VDR) antagonist. IL-10 expression was significantly stimulated by TNF-α and IL-1β, inhibited by IFN-γ and was not affected by IL-6. Finally, calcitriol inhibited TNF-α and IL-1β stimulation upon IL-10. In summary, in cultured human trophoblasts, calcitriol down-regulates IL-10 expression under normal as well as under natural and experimental inflammatory conditions. This effect is mediated by the VDR and might involve direct inhibition of TNF-α. In view of these and previous results it seems that in placenta calcitriol suppresses both Th1- and Th2 cytokines while undertakes the anti-inflammatory effects of IL-10 by itself, since both factors exert this task redundantly. The regulation of IL-10 by IFN-γ suggests that this cytokine could be a viable candidate to explain low IL-10 levels in preeclampsia.
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga, No. 15, Tlalpan, 14000 México D.F., Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Barrera
authors.forename: Nancy
authors.initials: N
authors.lastname: Noyola-Martínez
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: Lorenza
authors.initials: L
authors.lastname: Díaz
mesh_terms: D000328:Adult; D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000473:pathology*; D018836:Inflammation Mediators / Q000494:pharmacology; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D010920:Placenta / Q000473:pathology; D011225:Pre-Eclampsia / Q000235:genetics / Q000473:pathology; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014019:Tissue Donors; D014327:Trophoblasts / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
chemical_list: D006063:Chorionic Gonadotropin; C508609:IL10 protein, human; D018836:Inflammation Mediators; D012333:RNA, Messenger; C400545:TEI 9647; D016753:Interleukin-10; D002117:Calcitriol