Calcitriol inhibits interleukin-10 expression in cultured human trophoblasts under normal and inflammatory conditions

Cytokine. 2012 Mar;57(3):316-21. doi: 10.1016/j.cyto.2011.11.020. Epub 2011 Dec 17.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Calcitriol / analogs & derivatives
  • Calcitriol / pharmacology*
  • Cells, Cultured
  • Chorionic Gonadotropin / genetics
  • Chorionic Gonadotropin / metabolism
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / genetics
  • Inflammation / pathology*
  • Inflammation Mediators / pharmacology
  • Interleukin-10 / genetics*
  • Interleukin-10 / metabolism
  • Placenta / pathology
  • Pre-Eclampsia / genetics
  • Pre-Eclampsia / pathology
  • Pregnancy
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Time Factors
  • Tissue Donors
  • Trophoblasts / drug effects
  • Trophoblasts / metabolism*
  • Trophoblasts / pathology*

Substances

  • Chorionic Gonadotropin
  • IL10 protein, human
  • Inflammation Mediators
  • RNA, Messenger
  • TEI 9647
  • Interleukin-10
  • Calcitriol