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1 December 2006 Effects of 25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 on Cytokine Production by Human Decidual Cells
Katie N. Evans, Lisa Nguyen, Junny Chan, Barbara A. Innes, Judith N. Bulmer, Mark D. Kilby, Martin Hewison
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Abstract

The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) is a potent immunomodulatory seco-steroid. We have demonstrated that several components of vitamin D metabolism and signaling are strongly expressed in human uterine decidua from first trimester pregnancies, suggesting that locally produced 1,25(OH)2D3 may exert immunosuppressive effects during early stages of gestation. To investigate this further, we used primary cultures of human decidual cells from first and third trimester pregnancies to demonstrate expression and activity of the enzyme that catalyzes synthesis of 1,25(OH)2D3, 1alpha-hydroxylase (CYP27B1). Synthesis of 1,25(OH)2D3 was higher in first trimester decidual cells (41 ± 11.8 fmoles/h/mg protein) than in third trimester cells (8 ± 4.4 fmoles/h/mg protein; P < 0.05). Purification of decidual cells followed by quantitative RT-PCR analysis showed that CYP27B1 was expressed by both CD10 VE stromal-enriched and CD10−VE stromal-depleted cells, with higher levels of mRNA in first trimester pregnancies. Expression of CYP27B1 correlated with TLR4 and IDO. Functional responses to 1,25(OH)2D3 were studied using CD56 ve natural killer (NK) cells isolated from first trimester decidua. Decidual NK cells treated with 1,25(OH)2D3 or precursor 25-hydroxyvitamin D3 (25OHD3) for 28 h showed decreased synthesis of cytokines, such as granulocyte-macrophage colony stimulating factor 2 (CSF2), tumor necrosis factor, and interleukin 6, but increased expression of mRNA for the antimicrobial peptide cathelicidin antimicrobial peptide. These data indicate that human decidual cells are able to synthesize active 1,25(OH)2D3, particularly in early gestation, and this may act in an autocrine/paracrine fashion to regulate both acquired and innate immune responses at the fetal-maternal interface.

Katie N. Evans, Lisa Nguyen, Junny Chan, Barbara A. Innes, Judith N. Bulmer, Mark D. Kilby, and Martin Hewison "Effects of 25-Hydroxyvitamin D3 and 1,25-Dihydroxyvitamin D3 on Cytokine Production by Human Decidual Cells," Biology of Reproduction 75(6), 816-822, (1 December 2006). https://doi.org/10.1095/biolreprod.106.054056
Received: 22 May 2006; Accepted: 1 August 2006; Published: 1 December 2006
JOURNAL ARTICLE
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KEYWORDS
1α-hydroxylase
cytokines
decidua
natural killer cell
placenta
pregnancy,
steroid hormones
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