Vitamin D and the regulation of placental inflammation

Nancy Q Liu, Amber T Kaplan, Venu Lagishetty, Yuxin B Ouyang, Yi Ouyang, Charles F Simmons, Ozlem Equils, Martin Hewison

Research output: Contribution to journalArticlepeer-review

133 Citations (Scopus)


The vitamin D-activating enzyme 1α-hydroxylase (CYP27B1) and vitamin D receptor (VDR) support anti-inflammatory responses to vitamin D in many tissues. Given the high basal expression of CYP27B1 and VDR in trophoblastic cells from the placenta, we hypothesized that anti-inflammatory effects of vitamin D may be particularly important in this organ. Pregnant wild type (WT) mice i.p. injected with LPS showed elevated expression of mouse Cyp27b1 (4-fold) and VDR (6-fold). Similar results were also obtained after ex vivo treatment of WT placentas with LPS. To assess the functional impact of this, we carried out ex vivo studies using placentas -/- for fetal (trophoblastic) Cyp27b1 or VDR. Vehicle-treated -/- placentas showed increased expression of IFN-γ and decreased expression of IL-10 relative to +/+ placentas. LPS-treated -/- placentas showed increased expression of TLR2, IFN-γ, and IL-6. Array analyses identified other inflammatory factors that are dysregulated in Cyp27b1(-/-) versus Cyp27b1(+/+) placentas after LPS challenge. Data highlighted enhanced expression of IL-4, IL-15, and IL-18, as well as several chemokines and their receptors, in Cyp27b1(-/-) placentas. Similar results for IL-6 expression were observed with placentas -/- for trophoblastic VDR. Finally, ex vivo treatment of WT placentas with the substrate for Cyp27b1, 25-hydroxyvitamin D(3), suppressed LPS-induced expression of IL-6 and the chemokine Ccl11. These data indicate that fetal (trophoblastic) vitamin D plays a pivotal role in controlling placental inflammation. In humans, this may be a key factor in placental responses to infection and associated adverse outcomes of pregnancy.

Original languageEnglish
Pages (from-to)5968-74
Number of pages7
JournalJournal of Immunology
Issue number10
Publication statusPublished - 15 May 2011


  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Animals
  • Calcifediol
  • Chemokines
  • Female
  • Inflammation
  • Interferon-gamma
  • Interleukin-10
  • Interleukin-15
  • Interleukin-18
  • Interleukin-4
  • Interleukin-6
  • Lipopolysaccharides
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Placenta
  • Placenta Diseases
  • Polymerase Chain Reaction
  • Pregnancy
  • Receptors, Calcitriol
  • Toll-Like Receptor 2
  • Trophoblasts
  • Vitamin D


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