Hypoxia and P. gingivalis synergistically induce HIF-1 and NF-κB activation in PDL cells and periodontal diseases.

Hypoxia and P. gingivalis synergistically induce HIF-1 and NF-κB activation in PDL cells and periodontal diseases.
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DOI:
10.1155/2015/438085
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发表时间:
2015
影响因子:
4.6
通讯作者:
Frede S
Frede S
中科院分区:
医学3区
文献类型:
--
作者:
Gölz L;Memmert S;Rath-Deschner B;Jäger A;Appel T;Baumgarten G;Götz W;Frede S

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牙周炎的特征是牙周袋较深,有利于厌氧菌的增殖,如牙龈卟啉单胞菌(P.gigivalis),这种牙周病原体经常见于牙周炎患者。因此,本研究旨在探讨牙周膜(PDL)细胞在牙周膜(PDL)细胞中脂多糖(LPS-PG)和低氧激活的信号转导途径。检测相关转录因子核转录因子-kappaB(NF-κB)和缺氧诱导因子-1(HIF1)。此外,我们还从β和蛋白水平分析了白介素1、基质金属蛋白酶1和血管内皮生长因子的表达。这是通过健康和发炎的牙周组织的免疫组织化学完成的。我们检测了内毒素-PG和低氧对PDL细胞中NF-κB和H IF-1α活化的时间依赖性叠加效应,以及IL-1β、MMP1和VEGFmRNA表达的上调。对牙周炎和牙周炎组织标本的免疫组织化学检测显示,随着疾病的进展,NF-κB、HIF-1和VEGFI免疫反应增强,证实了体外实验结果的重要性。综上所述,本研究强调了NF-κB和HIF-1α及其靶基因β、IL-1和MMP1在牙周炎和低氧诱导的牙周炎过程中的意义。
Periodontitis is characterized by deep periodontal pockets favoring the proliferation of anaerobic bacteria like Porphyromonas gingivalis (P. gingivalis), a periodontal pathogen frequently observed in patients suffering from periodontal inflammation. Therefore, the aim of the present study was to investigate the signaling pathways activated by lipopolysaccharide (LPS) of P. gingivalis (LPS-PG) and hypoxia in periodontal ligament (PDL) cells. The relevant transcription factors nuclear factor-kappa B (NF-κB) and hypoxia inducible factor-1 (HIF-1) were determined. In addition, we analyzed the expression of interleukin- (IL-) 1β, matrix metalloproteinase-1 (MMP-1), and vascular endothelial growth factor (VEGF) in PDL cells on mRNA and protein level. This was accomplished by immunohistochemistry of healthy and inflamed periodontal tissues. We detected time-dependent additive effects of LPS-PG and hypoxia on NF-κB and HIF-1α activation in PDL cells followed by an upregulation of IL-1β, MMP-1, and VEGF expression. Immunohistochemistry performed on tissue samples of gingivitis and periodontitis displayed an increase of NF-κB, HIF-1, and VEGF immunoreactivity in accordance with disease progression validating the importance of the in vitro results. To conclude, the present study underlines the significance of NF-κB and HIF-1α and their target genes VEGF, IL-1β, and MMP-1 in P. gingivalis and hypoxia induced periodontal inflammatory processes.
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