title: Regulation of CYP27B1 and CYP24A1 gene expression by recombinant pro-inflammatory cytokines in cultured human trophoblasts.
abstract: 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.
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: Nancy
authors.initials: N
authors.lastname: Noyola-Martínez
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: Lorenza
authors.initials: L
authors.lastname: Díaz
authors.affiliation: Departamento de Biología Celular, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Montes Urales No. 800, Miguel Hidalgo 11000, México, D.F., Mexico.
authors.forename: Verónica
authors.initials: V
authors.lastname: Zaga-Clavellina
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: Euclides
authors.initials: E
authors.lastname: Avila
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: Ali
authors.initials: A
authors.lastname: Halhali
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: Fernando
authors.initials: F
authors.lastname: Larrea
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. Electronic address: barrera1912@gmail.com.
authors.forename: David
authors.initials: D
authors.lastname: Barrera
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D010920:Placenta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013250:Steroid Hydroxylases / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D000998:Antiviral Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
keywords: Calcitriol; Cytochromes P450; Placenta; Pregnancy; Vitamin D