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.
Cytokine. 2012 Mar;57(3):316-21. doi: 10.1016/j.cyto.2011.11.020. Epub 2011 Dec 17.
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-α (as an inflammatory stressor) were also performed. Calcitriol dose-dependently inhibited IL-10 expression in NT, PE and TNF-α-challenged trophoblasts (P<0.05). This effect was prevented by a vitamin D receptor (VDR) antagonist. IL-10 expression was significantly stimulated by TNF-α and IL-1β, inhibited by IFN-γ and was not affected by IL-6. Finally, calcitriol inhibited TNF-α and IL-1β 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-α. 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-γ suggests that this cytokine could be a viable candidate to explain low IL-10 levels in preeclampsia.
子痫前期与全身炎症和胎盘 Th1 细胞因子表达增加有关。IL-10 和钙三醇抑制人胎盘促炎细胞因子的表达，有助于胎儿同种异体移植物耐受。钙三醇和 Th1 细胞因子对胎盘 IL-10 的调节尚未完全阐明。由于人们认为钙三醇促进 Th1 向 Th2 表型的转变，我们假设它会在正常和炎症情况下刺激 IL-10，共同抑制炎症。因此，我们研究了钙三醇对正常（NT）和子痫前期（PE）妊娠中培养的人滋养层细胞中 IL-10 表达的影响。还进行了类似的研究，以 TNF-α（作为炎症应激源）存在。钙三醇剂量依赖性地抑制 NT、PE 和 TNF-α 刺激的滋养层细胞中 IL-10 的表达（P<0.05）。这种作用被维生素 D 受体（VDR）拮抗剂所阻止。IL-10 的表达受到 TNF-α 和 IL-1β 的刺激，受到 IFN-γ 的抑制，不受 IL-6 的影响。最后，钙三醇抑制 TNF-α和 IL-1β对 IL-10 的刺激。总之，在培养的人滋养层细胞中，钙三醇在正常以及自然和实验性炎症条件下下调 IL-10 的表达。这种作用是由 VDR 介导的，可能涉及对 TNF-α 的直接抑制。鉴于这些和以前的结果，似乎在胎盘，钙三醇抑制 Th1 和 Th2 细胞因子，同时通过自身承担 IL-10 的抗炎作用，因为这两个因素冗余地执行这一任务。IFN-γ 对 IL-10 的调节表明，这种细胞因子可能是解释子痫前期中 IL-10 水平降低的一个可行候选者。
