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牙龈卟啉单胞菌诱导的 THP1 细胞炎症反应受天然和修饰的低密度脂蛋白以菌株依赖性方式改变。

Porphyromonas gingivalis-induced inflammatory responses in THP1 cells are altered by native and modified low-density lipoproteins in a strain-dependent manner.

机构信息

Department of Medical Sciences, Örebro University, Örebro, Sweden.

出版信息

APMIS. 2018 Aug;126(8):667-677. doi: 10.1111/apm.12860.

Abstract

Strong epidemiological evidence supports an association between cardiovascular and periodontal disease and furthermore, the periodontopathogen Porphyromonas gingivalis has been identified in blood and from atheromatous plaques. Blood exposed to P. gingivalis shows an increased protein modification of low-density lipoprotein (LDL). In this study, we investigate the inflammatory responses of THP1 cells incubated with P. gingivalis and the effects of native or modified LDL on these responses. Reactive oxygen species (ROS) and IL-1β were observed in THP1 cells following infection with P. gingivalis ATCC33277 and W50. Caspase 1 activity was quantified in THP1 cells and correlated with IL-1β accumulation. Oxidized LDL (oxLDL) induced IL-1β release and CD36 expression on THP1 cells. Modified LDL co-stimulated with ATCC33277 exhibited regulatory effects on caspase 1 activity, IL-1β release and CD36 expression in THP1 cells, whereas W50 induced more modest responses in THP1 cells. In summary, we show that P. gingivalis is capable of inducing pro-inflammatory responses in THP1 cells, and native and modified LDL could alter these responses in a dose- and strain-dependent manner. Strain-dependent differences in THP1 cell responses could be due to the effect of P. gingivalis proteases, presence or absence of capsule and proteolytic transformation of native and modified LDL.

摘要

强有力的流行病学证据支持心血管疾病和牙周病之间存在关联,此外,牙周病原体牙龈卟啉单胞菌已在血液和动脉粥样硬化斑块中被发现。暴露于牙龈卟啉单胞菌的血液显示出低密度脂蛋白(LDL)的蛋白质修饰增加。在这项研究中,我们研究了与牙龈卟啉单胞菌孵育的 THP1 细胞的炎症反应,以及天然或修饰的 LDL 对这些反应的影响。在感染牙龈卟啉单胞菌 ATCC33277 和 W50 后,观察到 THP1 细胞中活性氧 (ROS) 和 IL-1β 的产生。在 THP1 细胞中定量测定了半胱天冬酶 1 的活性,并将其与 IL-1β 的积累相关联。氧化 LDL (oxLDL) 诱导 THP1 细胞释放 IL-1β 和表达 CD36。与 ATCC33277 共刺激的修饰 LDL 对 THP1 细胞中半胱天冬酶 1 活性、IL-1β 释放和 CD36 表达表现出调节作用,而 W50 对 THP1 细胞的诱导作用则较为温和。总之,我们表明牙龈卟啉单胞菌能够诱导 THP1 细胞产生促炎反应,天然和修饰的 LDL 可以以剂量和菌株依赖的方式改变这些反应。THP1 细胞反应的菌株依赖性差异可能是由于牙龈卟啉单胞菌蛋白酶的作用、荚膜的存在或缺失以及天然和修饰的 LDL 的蛋白水解转化所致。

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