Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA.
Cousins Center for Psychoneuroimmunology, Department of Psychiatry & Biobehavioral Sciences, Semel Institute for Neuroscience & Human Behavior, University of California, Los Angeles, USA.
Brain Behav Immun. 2020 Aug;88:654-660. doi: 10.1016/j.bbi.2020.04.065. Epub 2020 Apr 28.
Excessive inflammation in pregnancy predicts adverse birth outcomes, including shortened gestational length and lower birthweight, with African American women at greater risk. As substantial racial disparities in sleep quality, and evidence that African Americans have increased vulnerability for sleep-induced inflammatory dysregulation, sleep may be a critical, modifiable health behavior that contributes to racial disparities in birth outcomes. The present study examined sleep disturbance as a predictor of genome-wide transcriptome profiles of peripheral blood samples from 103 pregnant women (33 African American, 70 white) assessed at 18.7 ± 7.2 weeks gestation. We hypothesized that pregnant women with significant sleep disturbances would have gene expression profiles indicating over-expression of inflammatory pathways, with greater effects among African American compared to white women. Promoter-based bioinformatics analyses of differentially expressed genes indicated greater activation of NF-кB, AP1, and CREB transcription factors among African American women with sleep disturbances (all p < 0.05), and enhanced activation of AP1, but not NF-кB and reduced CREB activity among white women with sleep disturbances (p < 0.05). Differences in glucocorticoid receptor (GR) activity were also observed, in which African American women with sleep disturbances had reduced GR activity (p < 0.05), but white women with sleep disturbances showed a trend for enhanced GR activity (p = 0.11). Similarly, Interferon Response Factor (IRF) activity was reduced in African American women while increased in white women with sleep disturbances (p < 0.05). The current study provides novel evidence for gene expression related to inflammation, glucocorticoids, and anti-viral immunity among pregnant women with sleep disturbances, with differential effects by race. African Americans showed greater breadth and magnitude in these proinflammatory and anti-viral pathways than whites, with divergence in anti-inflammatory glucocorticoid, proinflammatory adrenergic-mediated cAMP, and anti-viral interferon responses. These data elucidate the role of sleep disturbances in intracellular inflammatory and anti-viral immunity in pregnancy and provide a potential target for intervention.
怀孕期间过度的炎症会预测不良的出生结局,包括缩短妊娠期和降低出生体重,非裔美国女性的风险更高。由于非裔美国人的睡眠质量存在显著差异,并且有证据表明非裔美国人对睡眠引起的炎症失调更为敏感,因此睡眠可能是一种重要的、可改变的健康行为,这种行为会导致出生结局的种族差异。本研究检查了睡眠障碍作为 103 名孕妇(33 名非裔美国人,70 名白人)外周血样本全基因组转录组谱的预测因子,这些孕妇在妊娠 18.7±7.2 周时接受了评估。我们假设,睡眠障碍严重的孕妇会有表明炎症途径过度表达的基因表达谱,而非裔美国女性的影响比白人女性更大。差异表达基因的启动子生物信息学分析表明,睡眠障碍的非裔美国女性中 NF-кB、AP1 和 CREB 转录因子的激活更为明显(所有 p<0.05),而睡眠障碍的白人女性中 AP1 的激活增强,而 NF-кB 和 CREB 活性降低(p<0.05)。还观察到糖皮质激素受体(GR)活性的差异,其中睡眠障碍的非裔美国女性的 GR 活性降低(p<0.05),但睡眠障碍的白人女性的 GR 活性有增强的趋势(p=0.11)。同样,睡眠障碍的非裔美国女性的干扰素反应因子(IRF)活性降低,而睡眠障碍的白人女性的 IRF 活性增加(p<0.05)。本研究为睡眠障碍孕妇的炎症、糖皮质激素和抗病毒免疫相关的基因表达提供了新的证据,并且存在种族差异。非裔美国女性在这些促炎和抗病毒途径中的广度和幅度都大于白人女性,抗炎糖皮质激素、促炎肾上腺素能介导的 cAMP 和抗病毒干扰素反应出现分歧。这些数据阐明了睡眠障碍在妊娠期间细胞内炎症和抗病毒免疫中的作用,并为干预提供了一个潜在的靶点。