Porphyromonas gingivalis induces IL-8 and IFN-gamma secretion and apoptosis in human extravillous trophoblast derived HTR8/SVneo cells via activation of ERK1/2 and p38 signaling pathways
Porphyromonas gingivalis induces IL-8 and IFN-gamma secretion and apoptosis in human extravillous trophoblast derived HTR8/SVneo cells via activation of ERK1/2 and p38 signaling pathways
复制标题
牙龈卟啉单胞菌通过激活 ERK1/2 和 p38 信号通路诱导人绒毛外滋养层来源的 HTR8/SVneo 细胞 IL-8 和 IFN-γ 分泌和细胞凋亡
DOI：
10.1016/j.placenta.2016.06.010
复制
发表时间：
2016
期刊：
影响因子：
3.8
通讯作者：
Minquan Du
中科院分区：
文献类型：
--
作者：
Hongyu Ren;Yuhong Li;Han Jiang;Minquan Du
前言：早产是导致婴儿死亡和发病的主要原因。大量研究表明，牙周病和早产之间存在联系。本研究的目的是探讨牙周病致病细菌牙龈卟啉单胞菌与人绒毛外滋养层细胞HTR8/SVneo细胞的相互作用。方法：采用双抗体夹心法测定HTR8细胞产生细胞因子的能力。Annexin V/PI流式细胞术检测细胞凋亡率。免疫印迹法检测蛋白质表达。用特定的药物抑制相关信号通路(p38MAPK，SB203580；ERK1/2，U0126；JNK，SP600125；NF-kB，jsh-23)，以确定它们在炎症和凋亡中的作用。结果：牙龈假单胞菌感染HTR8细胞后，HTR8细胞分泌大量IL-8和干扰素-g。同时，早期和晚期凋亡细胞的百分比都显著增加，以响应牙龈假单胞菌。抗炎作用最显著的是SB203580和U0126，其次是SP600125和JSH-23。此外，U0126和SB203580都部分但显著地抑制了牙龈假单胞菌诱导的细胞凋亡，U0126的作用更强。此外，热灭活的牙龈假单胞菌和牙龈假单胞菌的脂多糖均能显著诱导IL-8的产生。结论：牙龈假单胞菌可诱导HTR8细胞的炎症和凋亡，首次证实ERK1/2和p38MAPK信号通路的激活参与了牙龈假单胞菌诱导的炎症和细胞凋亡。牙龈假单胞菌感染对人滋养层细胞炎症和凋亡的异常调控，可能为研究母体牙周病和牙周病原体与早产的关系提供新的思路。
Introduction: Preterm birth is a major cause for infant mortality and morbidity. A large number of studies have suggested a link between periodontal disease and preterm birth. The purpose of this study was to investigate the interaction between a periodontopathic bacterium Porphyromonas gingivalis and human.extravillous trophoblast derived HTR8/SVneo cells. Methods: Production of cytokines in HTR8 cells was measured via ELISA. Annexin V/PI flow cytometry.was performed to assess apoptosis. Protein expression was measured by western blot. Specific pharmacological inhibitors were used to inactivate relevant signaling pathways (p38 MAPK, SB203580; ERK1/2, U0126; JNK, SP600125; NF-kB, JSH-23) to determine their roles in inflammation and apoptosis. Results: HTR8 cells released significant amounts of IL-8 and IFN-g during exposure to P. gingivalis. Meanwhile, the percentages of both early and late apoptotic cells increased significantly in response to P. gingivalis. The most significant effect on inflammation was found using SB203580 and U0126, followed.by SP600125 and JSH-23. Moreover, U0126 and SB203580 both partially but significantly suppressed P. gingivalis-induced apoptosis, with a large effect by U0126. Additionally, both heat-killed P. gingivalis and P. gingivalis lipopolysaccharide significantly induced IL-8 production. Conclusion: P. gingivalis induces inflammation and apoptosis in HTR8 cells, and we demonstrated for the first time that activation of ERK1/2 and p38 MAPK pathways participates in P. gingivalis-induced inflammation and apoptosis. The abnormal regulation of inflammation and apoptosis in human trophoblasts by P. gingivalis infection may give new insights into how maternal periodontal disease and periodontal pathogens might be linked to preterm birth.