title: IL-10 inhibits while calcitriol reestablishes placental antimicrobial peptides gene expression.
abstract: IL-10 and calcitriol help to achieve a successful pregnancy by suppressing active maternal immunity; however, these factors exert opposite effects upon microbial infections. In the skin and immune cells, IL-10 downregulates β-defensins while calcitriol induces cathelicidin gene expression in various tissues including placenta. Though, the regulation of human placental β-defensins by IL-10 and calcitriol has not been studied. Therefore, we explored the regulation of these antimicrobial peptides expression in cultured placental cells by calcitriol and IL-10 alone and combined. Real time PCR showed that calcitriol stimulated, while IL-10 inhibited, β-defensins and cathelicidin gene expression (P<0.05). In coincubations studies, calcitriol was able to maintain antimicrobial peptides gene expression above control values, overriding IL-10 inhibitory effects. Calcitriol downregulated endogenous IL-10 secretion. Interestingly, calcitriol and TNF-α cooperatively enhanced β-defensins, while TNF-α reduced basal and calcitriol-stimulated cathelicidin gene expression. In summary, calcitriol and IL-10 exerted opposite effects on antimicrobial peptides expression in the human placenta, suggesting that unbalanced production of IL-10 and calcitriol could be deleterious to innate immune responses during gestation. Our results suggest that calcitriol enhancement of placental defenses involves two mechanisms: (1) downregulation of IL-10 secretion and (2) direct upregulation of β-defensins and cathelicidin gene expression. Considering that IL-10 and calcitriol differentially regulate the innate immune response in the placenta, in the case of an infection, calcitriol might restrict IL-10 permissive actions towards microbial invasion while restrains inflammation, allowing for pregnancy to continue in quiescence. These results strongly advice maternal vitamin D sufficiency during pregnancy.
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, México City, Tlalpan 14000, Mexico.
authors.forename: Andrea
authors.initials: A
authors.lastname: Olmos-Ortiz
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, México City, Tlalpan 14000, 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, México City, Tlalpan 14000, Mexico.
authors.forename: David
authors.initials: D
authors.lastname: Barrera
authors.affiliation: Departamento de Inmunobioquímica, Instituto Nacional de Perinatología Isidro Espinosa de los Reyes, Montes Urales No. 800, México City, Col. Lomas de Virreyes 11000, 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, México City, Tlalpan 14000, 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, México City, Tlalpan 14000, Mexico.
authors.forename: Ali
authors.initials: A
authors.lastname: Halhali
authors.affiliation: División de Obstetricia, Hospital de Ginecología y Obstetricia del IMSS "Luis Castelazo Ayala", Río Magdalena No. 289, México City, Tizapán 01090, Mexico.
authors.forename: Benjamín
authors.initials: B
authors.lastname: Biruete
authors.affiliation: Departamento de Biología de la Reproducción, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga No. 15, México City, Tlalpan 14000, 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, México City, Tlalpan 14000, Mexico. Electronic address: lorenzadiaz@gmail.com.
authors.forename: Lorenza
authors.initials: L
authors.lastname: Díaz
mesh_terms: D000890:Anti-Infective Agents / Q000378:metabolism; D023181:Antimicrobial Cationic Peptides; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects; D016753:Interleukin-10 / Q000494:pharmacology*; D010920:Placenta / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology*; D023083:beta-Defensins / Q000235:genetics*; D054804:Cathelicidins
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; C422950:DEFB103A protein, human; C106641:DEFB4A protein, human; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D023083:beta-Defensins; D016753:Interleukin-10; D002117:Calcitriol; D054804:Cathelicidins
keywords: Cathelicidin; Innate defense; Placenta; β-Defensin