Calcitriol inhibits interleukin-10 expression in cultured human trophoblasts under normal and inflammatory conditions

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• 作者：David Barrera¹ ; Nancy Noyola-Martí ; nez¹ ; Euclides Avila ; Ali Halhali ; Fernando Larrea ; Lorenza Dí ; az ; ^{lorenzadiaz@gmail.com}
• 关键词：NT ; normal trophoblasts ; PE ; preeclampsia ; VDR ; vitamin D receptor ; CYP27B1 ; 25-OHD3-1-¦Á-hydroxylase ; CYP24A1 ; 25-hydroxyvitamin D3-24-hydroxylase ; 25-OHD3 ; 25-hydroxyvitamin D3 ; AMPs ; antimicrobial peptides ; TBP ; TATA-binding protein
• 刊名：Cytokine
• 出版年：2012
• 出版时间：March 2012
• 年：2012
• 卷：57
• 期：3
• 页码：316-321
• 全文大小：475 K

文摘

Preeclampsia is associated with systemic inflammation and increased expression of placental Th1-cytokines. IL-10 and calcitriol inhibit proinflammatory cytokines expression in human placenta helping to fetal allograft toleration. Regulation of placental IL-10 by calcitriol and Th-1 cytokines has not yet been fully elucidated. Since it is believed that calcitriol promotes a shift from a Th1- to a Th2 profile, we hypothesized that it would stimulate IL-10 in a normal and an inflammatory scenario to conjointly restrain inflammation. Therefore, we investigated calcitriol effects upon IL-10 expression in cultured human trophoblasts obtained from normal (NT) and preeclamptic (PE) pregnancies. Similar studies in the presence of TNF-¦Á (as an inflammatory stressor) were also performed. Calcitriol dose-dependently inhibited IL-10 expression in NT, PE and TNF-¦Á-challenged trophoblasts (P < 0.05). This effect was prevented by a vitamin D receptor (VDR) antagonist. IL-10 expression was significantly stimulated by TNF-¦Á and IL-1¦Â, inhibited by IFN-¦Ã and was not affected by IL-6. Finally, calcitriol inhibited TNF-¦Á and IL-1¦Â stimulation upon IL-10. In summary, in cultured human trophoblasts, calcitriol down-regulates IL-10 expression under normal as well as under natural and experimental inflammatory conditions. This effect is mediated by the VDR and might involve direct inhibition of TNF-¦Á. In view of these and previous results it seems that in placenta calcitriol suppresses both Th1- and Th2 cytokines while undertakes the anti-inflammatory effects of IL-10 by itself, since both factors exert this task redundantly. The regulation of IL-10 by IFN-¦Ã suggests that this cytokine could be a viable candidate to explain low IL-10 levels in preeclampsia.