Interferon-Gamma and Fas Are Involved in Porphyromonas gingivalis-Induced Apoptosis of Human Extravillous Trophoblast-Derived HTR8/SVneo Cells via Extracellular Signal-Regulated Kinase 1/2 Pathway
Interferon-Gamma and Fas Are Involved in Porphyromonas gingivalis-Induced Apoptosis of Human Extravillous Trophoblast-Derived HTR8/SVneo Cells via Extracellular Signal-Regulated Kinase 1/2 Pathway
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干扰素-γ 和 Fas 通过细胞外信号调节激酶 1/2 途径参与牙龈卟啉单胞菌诱导的人绒毛外滋养层来源的 HTR-8/SVneo 细胞凋亡
DOI：
10.1902/jop.2016.160259
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发表时间：
2016-11-01
影响因子：
4.3
通讯作者：
Du, Minquan
中科院分区：
文献类型：
--
作者：
Ren, Hongyu;Li, Yuhong;Du, Minquan
背景：最近的一些研究揭示了牙周病和早产（PTB）之间的联系。PTB可由牙龈卟啉单胞菌（Porphyromonas gingivalis，Pg）的牙齿感染诱导，所述牙龈卟啉单胞菌是牙周病细菌。本研究旨在探讨人绒毛外滋养层细胞HTR 8/SVneo细胞对Pg感染的反应。方法：分别采用流式细胞术、CCK-8法、Western blot法和酶联免疫吸附法检测HTR 8细胞凋亡、细胞活力、蛋白表达和细胞因子产生。在HTR 8细胞中，PG降低细胞活力并增加细胞凋亡、活性半胱天冬酶-3和Fas表达以及干扰素-γ（IFN-γ）分泌。细胞外信号调节激酶（ERK）1/2抑制剂U 0126和FasL中和抗体NOK 1，阻断FasL/Fas相互作用都显着抑制PG诱导的细胞凋亡。U 0126还抑制IFN-γ分泌和Fas表达，接近对照水平。此外，重组IFN-γ处理后HTR 8细胞存活率显著降低，Fas表达增加，提示IFN-γ可能在前列腺素诱导的HTR 8细胞凋亡中起重要作用，至少部分通过调节Fas表达。据作者所知，这是第一项证明Pg诱导IFN-γ分泌，Fas表达，人绒毛外滋养层细胞来源的HTR 8/SVneo细胞以ERK 1/2依赖的方式发生凋亡，IFN-γ（通过重组IFN-γ探索）和Fas参与Pg诱导的凋亡。Pg感染异常调节人类滋养层细胞的炎症和凋亡的发现可能为PTB与母体牙周疾病和牙周病原体的可能联系提供新的见解。
Background: A number of studies recently revealed a link between periodontal disease and preterm birth (PTB). PTB can be induced by dental infection with Porphyromonas gingivalis (Pg), a periodontopathic bacterium. This study aims to investigate responses of human extravillous trophoblast-derived HTR8/SVneo cells to Pg infection.Methods: Cell apoptosis, cell viability, protein expression, and cytokine production in HTR8 cells were measured via: 1) flow cytometry, 2) CCK-8 assay, 3) western blot, and 4) enzyme-linked immunosorbent assay methods, respectively.Results: Pg decreased cell viability and increased cell apoptosis, active caspase-3 and Fas expression, and interferon-gamma (IFN-gamma) secretion in HTR8 cells. Extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 and FasL neutralizing antibody NOK1 that blocks FasL/Fas interaction both significantly suppressed Pg-induced apoptosis. U0126 also inhibited IFN-gamma secretion and Fas expression close to control levels. Moreover, treatment with recombinant IFN-gamma also significantly decreased number of viable HTR8 cells and increased Fas expression, suggesting IFN-gamma may play an important role in Pg-induced apoptosis of HTR8 cells, at least partially through regulation of Fas expression.Conclusions: To the best of the authors' knowledge, this is the first study to demonstrate Pg induces IFN-g secretion, Fas expression, and apoptosis in human extravillous trophoblast-derived HTR8/SVneo cells in an ERK1/2-dependent manner, and IFN-gamma (explored by recombinant IFN-gamma) and Fas are involved in Pg-induced apoptosis. The finding that Pg infection abnormally regulates inflammation and apoptosis of human trophoblasts may give new insights into the possible link of PTB with maternal periodontal disease and periodontal pathogens.