Angiotensin-(1-7) Peptide Hormone Reduces Inflammation and Pathogen Burden during Mycoplasma pneumoniae Infection in Mice.

Angiotensin-(1-7) Peptide Hormone Reduces Inflammation and Pathogen Burden during Mycoplasma pneumoniae Infection in Mice.
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血管紧张素-(1-7)肽激素可降低小鼠肺炎支原体感染时的炎症和病原体负担。

DOI:
10.3390/pharmaceutics13101614
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发表时间:
2021-10-04
期刊:
影响因子:
5.4
通讯作者:
Ledford JG
Ledford JG
中科院分区:
医学2区
文献类型:
--
作者:
Collins KL;Younis US;Tanyaratsrisakul S;Polt R;Hay M;Mansour HM;Ledford JG

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肽激素血管紧张素(Ang-(1-7))通过抑制与细胞因子风暴相关的许多细胞因子和粘附分子的产生和表达而产生抗炎和保护作用。虽然Ang-(1-7)已显示在哮喘模型中减少炎症和气道高反应性,但关于Ang-(1-7)在活体呼吸道感染中的作用知之甚少。我们的研究旨在测试Ang-(1-7)是否在肺炎支原体(MP)感染期间保护肺免受过度的免疫应答,肺炎支原体是一种常见的呼吸道病原体,已知可引起哮喘和COPD患者的急性加重。用感染性Mp处理野生型小鼠,并在感染后2小时内通过口咽递送给予一个亚组Ang-(1-7)或无肽载体。在24小时内评估每组动物的肺部炎症标志物。在支原体感染期间,一个高剂量的Ang-(1-7)递送到肺减少嗜中性粒细胞和Muc 5ac,以及与急性呼吸窘迫综合征(ARDS)相关的TNF-α和趋化因子(Cxcl 1)。尽管炎症减少,但Ang-(1-7)治疗的小鼠肺组织中的Mp负荷也显着降低,表明气道定植减少。Ang-(1-7)还通过剂量依赖性地抑制TNF-α的产生同时促进Mp杀伤而对RAW 264.7细胞(一种常用的巨噬细胞系)产生影响。这些新发现为Ang 1 -7在控制炎症中的保护作用提供了额外的支持,我们发现Ang 1 -7对活MP诱导的肺部炎症具有高度保护作用。
The peptide hormone, angiotensin (Ang-(1–7)), produces anti-inflammatory and protective effects by inhibiting production and expression of many cytokines and adhesion molecules that are associated with a cytokine storm. While Ang-(1–7) has been shown to reduce inflammation and airway hyperreactivity in models of asthma, little is known about the effects of Ang-(1–7) during live respiratory infections. Our studies were developed to test if Ang-(1–7) is protective in the lung against overzealous immune responses during an infection with Mycoplasma pneumonia (Mp), a common respiratory pathogen known to provoke exacerbations in asthma and COPD patients. Wild type mice were treated with infectious Mp and a subset of was given either Ang-(1–7) or peptide-free vehicle via oropharyngeal delivery within 2 h of infection. Markers of inflammation in the lung were assessed within 24 h for each set of animals. During Mycoplasma infection, one high dose of Ang-(1–7) delivered to the lungs reduced neutrophilia and Muc5ac, as well as Tnf-α and chemokines (Cxcl1) associated with acute respiratory distress syndrome (ARDS). Despite decreased inflammation, Ang-(1-7)-treated mice also had significantly lower Mp burden in their lung tissue, indicating decreased airway colonization. Ang-(1–7) also had an impact on RAW 264.7 cells, a commonly used macrophage cell line, by dose-dependently inhibiting TNF-α production while promoting Mp killing. These new findings provide additional support to the protective role(s) of Ang1-7 in controlling inflammation, which we found to be highly protective against live Mp-induced lung inflammation.
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