Regulation of CYP27B1 and CYP24A1 gene expression by recombinant pro-inflammatory cytokines in cultured human trophoblasts

• Published in: The Journal of steroid biochemistry and molecular biology 2014-10, Vol.144, p.106-109
• Main Authors: Noyola-Martínez, Nancy, Díaz, Lorenza, Zaga-Clavellina, Verónica, Avila, Euclides, Halhali, Ali, Larrea, Fernando, Barrera, David
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Antiviral Agents - pharmacology; Calcitriol; Cells, Cultured; Cytochromes P450; Enzyme-Linked Immunosorbent Assay; Female; Gene Expression Regulation - drug effects; Humans; Interferon-gamma - pharmacology; Interleukin-1beta - pharmacology; Interleukin-6 - pharmacology; Placenta; Placenta - cytology; Placenta - drug effects; Placenta - metabolism; Pregnancy; Real-Time Polymerase Chain Reaction; Recombinant Proteins - genetics; Recombinant Proteins - pharmacology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; Steroid Hydroxylases - genetics; Steroid Hydroxylases - metabolism; Trophoblasts - cytology; Trophoblasts - drug effects; Trophoblasts - metabolism; Tumor Necrosis Factor-alpha - pharmacology; Vitamin D; Vitamin D3 24-Hydroxylase
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/j.jsbmb.2013.12.007

•Cytokines regulate calcitriol metabolism in human placenta.•INFγ contributes to calcitriol anabolism.•TNFα favors the catabolism of calcitriol. Placenta is an important source of endocrine and immunological factors. During pregnancy, calcitriol, the active metabolite of vitamin D, is also metabolized by decidua and placental tissue by means of CYP27B1 and CYP24A1 for synthesis and inactivation of calcitriol respectively. Calcitriol production is regulated by several factors in a tissue-specific manner. However, the association of pro-inflammatory cytokines on calcitriol metabolism has not been studied in human placenta. The aim of the present study was to investigate the effects of TNF-α, INF-γ, IL-6 and IL-1β upon CYP27B1 and CYP24A1 gene expression in primary cultures of human placental cells. Placentas were obtained immediately after delivery by cesarean section from normotensive women. Cytokine effects upon mRNA of CYPs in enriched trophoblastic cell preparations were evaluated by using qPCR. The results showed that incubation of trophoblasts in the presence of each cytokine resulted in a significant increase of both CYPs expression. Interestingly, TNF-α increased significantly the ratio of CYP24A1/CYP27B1 gene expression, while IFN-γ preferentially induced CYP27B1, whereas IL-1β and IL-6 stimulated gene expression of both CYPs in the same proportion. The results suggest that cytokines among other factors regulate calcitriol metabolism in human placenta; specifically, INF-γ may contribute to calcitriol production while TNF-α favors its catabolism.