Migale Roberta, Herbert Bronwen R, Lee Yun S, Sykes Lynne, Waddington Simon N, Peebles Donald, Hagberg Henrik, Johnson Mark R, Bennett Phillip R, MacIntyre David A
Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom.
Imperial College Parturition Research Group, Institute of Reproductive and Developmental Biology, Imperial College London, London, United Kingdom; Academic Department of Obstetrics and Gynaecology, Chelsea and Westminster Hospital, London, United Kingdom.
Am J Pathol. 2015 Sep;185(9):2390-401. doi: 10.1016/j.ajpath.2015.05.015. Epub 2015 Jul 26.
Intrauterine inflammation is recognized as a key mediator of both normal and preterm birth but is also associated with neonatal neurological injury. Lipopolysaccharide (LPS) is often used to stimulate inflammatory pathways in animal models of infection/inflammation-induced preterm labor; however, inconsistencies in maternal and neonatal responses to LPS are frequently reported. We hypothesized that LPS serotype-specific responses may account for a portion of these inconsistencies. Four different Escherichia coli LPS serotypes (O111:B4, O55:B5, O127:B8, and O128:B12) were administered to CD1 mice via intrauterine injection at gestational day 16. Although control animals delivered at term 60 ± 15 hours postinjection (p.i.), those administered with O111:B4 delivered 7 ± 2 hours p.i., O55:B5 delivered 10 ± 3 hours p.i., O127:B8 delivered 16 ± 10 hours p.i., and O128:B12 delivered 17 ± 2 hours p.i. (means ± SD). A correlation between the onset of preterm labor and myometrial activation of the inflammatory transcription factor, activator protein 1, but not NF-κB was observed. Specific LPS serotypes induced differential activation of downstream contractile and inflammatory pathways in myometrium and neonatal pup brain. Our findings demonstrate functional disparity in inflammatory pathway activation in response to differing LPS serotypes. Selective use of LPS serotypes may represent a useful tool for targeting specific inflammatory response mechanisms in these models.
宫内炎症被认为是正常分娩和早产的关键介质，但也与新生儿神经损伤有关。脂多糖（LPS）常用于在感染/炎症诱导的早产动物模型中刺激炎症途径；然而，经常报道母体和新生儿对LPS的反应存在不一致性。我们推测LPS血清型特异性反应可能是这些不一致性的部分原因。在妊娠第16天通过宫内注射将四种不同的大肠杆菌LPS血清型（O111:B4、O55:B5、O127:B8和O128:B12）给予CD1小鼠。尽管对照动物在注射后60±15小时足月分娩，但给予O111:B4的动物在注射后7±2小时分娩，给予O55:B5的动物在注射后10±3小时分娩，给予O127:B8的动物在注射后16±10小时分娩，给予O128:B12的动物在注射后17±2小时分娩（平均值±标准差）。观察到早产发作与子宫肌层中炎症转录因子激活蛋白1的激活之间存在相关性，但与核因子κB无关。特定的LPS血清型在子宫肌层和新生幼崽脑中诱导下游收缩和炎症途径的差异激活。我们的研究结果表明，对不同LPS血清型的炎症途径激活存在功能差异。选择性使用LPS血清型可能是在这些模型中靶向特定炎症反应机制的有用工具。
