PlGF 增强人类单核吞噬细胞中 TLR 依赖性炎症反应。
PlGF enhances TLR-dependent inflammatory responses in human mononuclear phagocytes.
机构信息
Hematology and Medical Oncology, Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA.
Division of Hematology, Oncology and Transplant, University of Minnesota, Minneapolis, MN, USA.
出版信息
Am J Reprod Immunol. 2017 Oct;78(4). doi: 10.1111/aji.12709. Epub 2017 Jun 20.
PROBLEM
Levels of placental growth factor (PlGF) peak during third trimester of pregnancy, a time when women are at increased risk of virus-induced morbidity. We hypothesized PlGF might contribute to an exaggerated inflammatory response to Toll-like receptor (TLR) activation.
METHOD OF STUDY
Primary human adult and cord blood CD14 cells were cultured in the presence of TLR ligands and/or PlGF.
RESULTS
PlGF significantly enhanced the magnitude and duration of TNF messenger RNA and protein production by TLR-7/8-activated monocytes, and increased subsequent production of TNF-independent inflammatory cytokines. This PlGF/TLR effect involved multiple inflammatory cytokines/chemokines and was seen with the majority of TLR agonists. PlGF enhanced phosphorylation of IkappaB kinase (IKK) in monocytes stimulated with the TLR-7/8 agonist R848, and IKK inhibition completely suppressed the PlGF effect.
CONCLUSION
PlGF enhances TLR-signaling upstream of IKK and contributes to an exaggerated pathologic pro-inflammatory state in response to activation of maternal and fetal mononuclear phagocytes by specific TLR agonists.
问题
胎盘生长因子 (PlGF) 的水平在妊娠晚期达到峰值，此时女性患病毒诱导疾病的风险增加。我们假设 PlGF 可能导致 Toll 样受体 (TLR) 激活的炎症反应过度。
研究方法
原代人成人和脐带血 CD14 细胞在 TLR 配体和/或 PlGF 的存在下培养。
结果
PlGF 显著增强了 TLR-7/8 激活的单核细胞中 TNF 信使 RNA 和蛋白的产生幅度和持续时间，并增加了随后产生的 TNF 非依赖性炎症细胞因子。这种 PlGF/TLR 效应涉及多种炎症细胞因子/趋化因子，并且与大多数 TLR 激动剂都有关。PlGF 增强了 TLR-7/8 激动剂 R848 刺激的单核细胞中 IKK 的磷酸化，而 IKK 抑制完全抑制了 PlGF 的作用。
结论
PlGF 在 IKK 上游增强 TLR 信号传导，并导致母体和胎儿单核吞噬细胞被特定 TLR 激动剂激活时，过度病理促炎状态。
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