School of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
Reprod Sci. 2011 Jan;18(1):88-98. doi: 10.1177/1933719110380470. Epub 2010 Oct 5.
Inflammation is a defensive process by which the body responds to both localized and systemic tissue damage by the induction of innate and adaptive immunity. Literature from human and animal studies links inappropriate in utero inflammation to preterm parturition and fetal injury. The pathways by which such inflammation may cause labor, however, are not fully understood. Any proinflammatory agonist in the amniotic fluid will contact the fetal skin, in its entirety, but a potential role of the fetal skin in the pathways to labor have not previously been explored. We hypothesized that the fetal skin would respond robustly to the presence of intra-amniotic lipopolysaccharide (LPS) in our ovine model of in utero inflammation. In vitro and in utero exposure of fetal ovine keratinocytes or fetal skin to Escherichia coli LPS reliably induced significant increases in interleukin 1β (IL-1β), IL-6, tumor necrosis factor α (TNF-α), and IL-8 expression. We demonstrate that, in utero, this expression requires direct exposure with LPS suggesting that the inflammation is triggered directly in the skin itself, rather than as a secondary response to a systemic stimuli and that inflammation involves Toll-like receptor (TLR) regulation and neutrophil chemotaxis in concordance with an acute inflammatory reaction. We show that this response involves multiple inflammatory mediators, TLR regulation, and localized inflammatory cell influx characteristic of an acute inflammatory reaction. These novel data strongly suggests that the fetal skin acts as an important mediator of the fetal inflammatory response and as such may contribute to preterm birth.
炎症是一种防御过程，通过诱导先天和适应性免疫，身体对局部和全身组织损伤做出反应。来自人类和动物研究的文献将宫内炎症与早产和胎儿损伤联系起来。然而，导致这种炎症导致分娩的途径尚不完全清楚。羊水中的任何促炎激动剂都会与胎儿皮肤的全部接触，但胎儿皮肤在分娩途径中的潜在作用以前没有被探索过。我们假设胎儿皮肤会对羊水中的内毒素（LPS）的存在做出强烈反应，这是我们在宫内炎症羊模型中的假设。体外和体内暴露于大肠杆菌 LPS 的胎儿羊角质形成细胞或胎儿皮肤可靠地诱导白细胞介素 1β（IL-1β）、IL-6、肿瘤坏死因子α（TNF-α）和 IL-8 表达显著增加。我们证明，在宫内，这种表达需要直接暴露于 LPS，这表明炎症是直接在皮肤本身触发的，而不是对全身刺激的二级反应，并且炎症涉及 Toll 样受体（TLR）调节和与急性炎症反应一致的中性粒细胞趋化性。我们表明，这种反应涉及多种炎症介质、TLR 调节和局部炎症细胞浸润，这是急性炎症反应的特征。这些新数据强烈表明，胎儿皮肤是胎儿炎症反应的重要介质，因此可能导致早产。
