Division of Reproductive and Developmental Sciences, University of Edinburgh, Centre for Reproductive Biology, 47 Little France Crescent, Edinburgh EH16 4TJ, UK.
FASEB J. 2011 Feb;25(2):569-75. doi: 10.1096/fj.10-170340. Epub 2010 Oct 19.
The purpose of this study was to investigate the role of lipoxin A(4), an anti-inflammatory and proresolution modulator, during human parturition. We measured serum levels of lipoxin A(4) and myometrial protein release using ELISA, quantified lipoxin receptor (FPR2/ALX) mRNA expression using qRT-PCR, and localized protein expression using immunohistochemstry in myometrial biopsies from pregnant women. In addition, we compared the effects of lipoxin A(4) (100 nM) with vehicle on basal and LPS-stimulated expression of proinflammatory cytokines from samples of myometrium from pregnant women. Mean ± SE circulating level of lipoxin A(4) was 5.89 ± 0.63 nM at 24-wk gestation, with a further modest increase during pregnancy (P<0.05), but no differences in gestation matched women before and after labor (P>0.05). Levels of lipoxin A(4) in nonpregnant women were 0.48 ± 0.04 nM, significantly lower than in pregnant women (P<0.001). FPR2/ALX localized to myocytes and neutrophils, with a 9-fold increase in mRNA expression in labor (P<0.001). Lipoxin A(4) significantly reduced LPS-induced but not basal expression of the proinflammatory cytokines IL-6 and IL-8 in cultured myometrium (P<0.05), compared to vehicle-treated controls. We demonstrate for the first time a potential role for lipoxin A(4) and its receptor in the resolution of the inflammatory events of both physiological and pathological labor.
本研究旨在探讨脂氧素 A（4）（一种抗炎和促解决调节剂）在人类分娩过程中的作用。我们使用 ELISA 测量了血清中的脂氧素 A（4）水平和子宫肌蛋白释放，使用 qRT-PCR 定量了脂氧素受体（FPR2/ALX）mRNA 表达，并使用免疫组织化学在来自孕妇的子宫肌活检中定位了蛋白质表达。此外，我们比较了脂氧素 A（4）（100 nM）与载体对来自孕妇子宫肌样本的基础和 LPS 刺激的促炎细胞因子表达的影响。24 周妊娠时，脂氧素 A（4）的平均±SE 循环水平为 5.89±0.63 nM，妊娠期间略有增加（P<0.05），但分娩前后妊娠匹配妇女之间没有差异（P>0.05）。非孕妇的脂氧素 A（4）水平为 0.48±0.04 nM，明显低于孕妇（P<0.001）。FPR2/ALX 定位于肌细胞和中性粒细胞，分娩时 mRNA 表达增加 9 倍（P<0.001）。与载体处理的对照组相比，脂氧素 A（4）显著降低了 LPS 诱导但不降低基础表达的促炎细胞因子 IL-6 和 IL-8 在培养的子宫肌中（P<0.05）。我们首次证明了脂氧素 A（4）及其受体在生理和病理性分娩中炎症事件的解决中具有潜在作用。
