IL-10 inhibits while calcitriol reestablishes placental antimicrobial peptides gene expression. Issue 148 (April 2015)

• Record Type: Journal Article
• Authors: Olmos-Ortiz, Andrea; Noyola-Martínez, Nancy; Barrera, David; Zaga-Clavellina, Verónica; Avila, Euclides; Halhali, Ali; Biruete, Benjamín; Larrea, Fernando; Díaz, Lorenza
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 148(2015)
• Page Start: 187
• Page End: 193
• Publication Date: 2015-04
• Subjects: VD Vitamin D3 -- AMP Antimicrobial peptide -- HBD Human β-defensin -- hCTD Cathelicidin -- ETC Enriched trophoblastic cell preparations -- CK-7 Cytokeratin 7; Cathelicidin -- β-Defensin -- Innate defense -- Placenta; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2014.07.012
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Calcitriol upregulates placental β-defensins and cathelicidin gene expression. IL-10 inhibits placental HBD2, HBD3 and cathelicidin gene expression. TNF-α and calcitriol cooperatively enhance placental β-defensins. TNF-α reduces basal and calcitriol-stimulated cathelicidin 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.