Prolactin (PRL) plays an important role in trophoblast growth, placental angiogenesis and immunomodulation within the feto-maternal interface, where different cell types secrete PRL and express its receptor. During pregnancy, inflammatory signalling is a deleterious event that has been associated with poor fetal outcomes. The placenta is highly responsive to the inflammatory stimulus; however, the actions of PRL in placental immunity and inflammation remain largely unknown. The aim of this study was to evaluate PRL effects on the TLR4/NFkB signalling cascade and associated inflammatory targets in cultured explants from healthy term human placentas. An in utero inflammatory scenario was mimicked using lipopolysaccharides (LPS) from Escherichia coli. PRL significantly reduced LPS-dependent TNF-α, IL-1β and IL-6 secretion and intracellular levels. Mechanistically, PRL prevented LPS-mediated upregulation of TLR-4 expression and NFκB phosphorylation. In conclusion, PRL limited inflammatory responses to LPS in the human placenta, suggesting that this hormone could be critical in inhibiting exacerbated immune responses to infections that could threaten pregnancy outcome. This is the first evidence of a mechanism for anti-inflammatory activity of PRL in the human placenta, acting as a negative regulator of TLR-4/NFkB signaling.

中文翻译：

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催乳素通过抑制人胎盘中的TLR-4 /NFκB信号传导来降低LPS诱导的炎性细胞因子。

催乳素（PRL）在胎儿-母亲界面内的滋养细胞生长，胎盘血管生成和免疫调节中起重要作用，其中不同类型的细胞分泌PRL并表达其受体。在怀孕期间，炎症信号是有害的事件，与不良的胎儿预后有关。胎盘对炎性刺激高度敏感。然而，PRL在胎盘免疫和炎症中的作用仍然未知。这项研究的目的是评估PRL对健康术语人类胎盘培养的外植体中TLR4 / NFkB信号级联和相关炎症靶标的影响。使用大肠杆菌的脂多糖（LPS）模仿子宫内炎症。PRL显着降低LPS依赖性TNF-α，IL-1β和IL-6的分泌以及细胞内水平。从机制上讲，PRL阻止了LPS介导的TLR-4表达上调和NFκB磷酸化。总之，PRL限制了人类胎盘对LPS的炎性反应，表明该激素在抑制对可能威胁妊娠结局的感染的加剧免疫反应中至关重要。这是人胎盘中PRL抗炎活性机制的第一个证据，它是TLR-4 / NFkB信号的负调节剂。