Th1-type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II-dependent hypertension and vascular dysfunction.
Th1-type immune responses to Porphyromonas gingivalis antigens exacerbate angiotensin II-dependent hypertension and vascular dysfunction.
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DOI：
10.1111/bph.14536
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发表时间：
2019-06
影响因子：
7.3
通讯作者：
Guzik TJ
中科院分区：
文献类型：
--
作者：
Czesnikiewicz-Guzik M;Nosalski R;Mikolajczyk TP;Vidler F;Dohnal T;Dembowska E;Graham D;Harrison DG;Guzik TJ
新的证据表明高血压是由免疫机制介导的。我们假设，暴露于牙周病中常见的牙龈卟啉单胞菌抗原可以增强高血压患者的免疫激活，并加剧血压升高、血管炎症和血管功能障碍。通过使用与氧化铝 (50 μg) 和 IL-12 (1 μg) 结合的牙龈卟啉单胞菌裂解物抗原 (10 μg) 进行免疫接种，引发 Th1 免疫反应。研究了低剂量血管紧张素 II (0.25 mg·kg−1·day−1) 引起的高血压和血管内皮功能障碍，并通过流式细胞术和实时 PCR 定量血管炎症。牙龈卟啉单胞菌抗原刺激会加剧全身性 T 细胞激活，这是高血压的一个特征。这转化为主动脉血管炎症增加，白细胞（特别是 T 细胞和巨噬细胞浸润）增强。在牙龈卟啉单胞菌/IL-12/氧化铝免疫小鼠的主动脉中，Th1 细胞因子 IFN-γ 和 TNF-α 以及转录因子 TBX21 的表达增加，而 IL-4 和 TGF-β 则没有变化。与对照小鼠相比，诱导 1 型 T 辅助细胞免疫反应的小鼠的这些免疫变化与血压升高和内皮功能障碍有关，这些变化与输注 2 周亚加压剂量的血管紧张素 II 后的反应有关。这些结果支持这样的观点，即牙龈卟啉单胞菌等细菌抗原诱导的 Th1 免疫反应可以增加对低剂量血管紧张素 II 等降压促高血压损伤的敏感性，从而提供牙周炎等慢性感染与高血压之间的机制联系。本文是高血压免疫目标主题部分的一部分。要查看本节中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Emerging evidence indicates that hypertension is mediated by immune mechanisms. We hypothesized that exposure to Porphyromonas gingivalis antigens, commonly encountered in periodontal disease, can enhance immune activation in hypertension and exacerbate the elevation in BP, vascular inflammation and vascular dysfunction. Th1 immune responses were elicited through immunizations using P. gingivalis lysate antigens (10 μg) conjugated with aluminium oxide (50 μg) and IL‐12 (1 μg). The hypertension and vascular endothelial dysfunction evoked by subpressor doses of angiotensin II (0.25 mg·kg−1·day−1) were studied, and vascular inflammation was quantified by flow cytometry and real‐time PCR. Systemic T‐cell activation, a characteristic of hypertension, was exacerbated by P. gingivalis antigen stimulation. This translated into increased aortic vascular inflammation with enhanced leukocyte, in particular, T‐cell and macrophage infiltration. The expression of the Th1 cytokines, IFN‐γ and TNF‐α, and the transcription factor, TBX21, was increased in aortas of P. gingivalis/IL‐12/aluminium oxide‐immunized mice, while IL‐4 and TGF‐β were unchanged. These immune changes in mice with induced T‐helper‐type 1 immune responses were associated with an enhanced elevation of BP and endothelial dysfunction compared with control mice in response to 2 week infusion of a subpressor dose of angiotensin II. These results support the concept that Th1 immune responses induced by bacterial antigens such as P. gingivalis can increase sensitivity to subpressor pro‐hypertensive insults such as low‐dose angiotensin II, thus providing a mechanistic link between chronic infection, such as periodontitis, and hypertension. This article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
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血管紧张素II依赖性高血压的性别特异性T细胞调节。
DOI：
10.1161/hypertensionaha.114.03663
发表时间：
2014-09
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
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通讯作者：
Sandberg K
影响因子：
10.8
作者：
Guzik TJ;Skiba DS;Touyz RM;Harrison DG
通讯作者：
Harrison DG
影响因子：
4.4
作者：
Ely, KH;Cauley, LS;Woodland, DL
通讯作者：
Woodland, DL
影响因子：
5.4
作者：
Hoeve, MA;Savage, NDL;Verreck, FAW
通讯作者：
Verreck, FAW
DOI：
10.1073/pnas.1203543109
发表时间：
2012-06-19
影响因子：
11.1
作者：
Freeman, Bailey E.;Hammarlund, Erika;Slifka, Mark K.
通讯作者：
Slifka, Mark K.