Abstract：
OBJECTIVE: Angiotensin-(1-7) [Ang-(1-7)] is a pro-resolving mediator. It is not known whether the pro-resolving effects of Ang-(1-7) are sustained and protect the lung from a subsequent inflammatory challenge. This study sought to investigate the impact of treatment in face of a second allergic or lipopolysaccharide (LPS) challenge.
METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed.
RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation.
CONCLUSIONS: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.
METHODS: Mice, sensitized and challenged with ovalbumin (OVA), received a single Ang-(1-7) dose at the peak of eosinophilic inflammation, 24 h after the final OVA challenge. Subsequently, mice were euthanized at 48, 72, 96, and 120 h following the OVA challenge, and cellular infiltrate, inflammatory mediators, lung histopathology, and macrophage-mediated efferocytic activity were evaluated. The secondary inflammatory stimulus (OVA or LPS) was administered 120 h after the last OVA challenge, and subsequent inflammatory analyses were performed.
RESULTS: Treatment with Ang-(1-7) resulted in elevated levels of IL-10, CD4+Foxp3+, Mres in the lungs and enhanced macrophage-mediated efferocytic capacity. Moreover, in allergic mice treated with Ang-(1-7) and then subjected to a secondary OVA challenge, inflammation was also reduced. Similarly, in mice exposed to LPS, Ang-(1-7) effectively prevented the lung inflammation.
CONCLUSIONS: A single dose of Ang-(1-7) resolves lung inflammation and protect the lung from a subsequent inflammatory challenge highlighting its potential therapeutic for individuals with asthma.
摘要：
目的:血管紧张素-(1-7)[Ang-(1-7)]是促分解介质。尚不清楚Ang-(1-7)的促解作用是否持续并保护肺免受随后的炎性攻击。这项研究旨在研究面对第二次过敏或脂多糖（LPS）挑战时治疗的影响。
方法：小鼠，致敏和攻击卵清蛋白（OVA），在嗜酸性粒细胞炎症的高峰期接受单一剂量的Ang-（1-7），最终OVA挑战后24小时。随后，小鼠在OVA攻击后48、72、96和120小时安乐死，细胞浸润，炎症介质，肺组织病理学,和巨噬细胞介导的白细胞活性进行了评估。在最后一次OVA攻击后120小时给予继发性炎症刺激（OVA或LPS），随后进行炎症分析.
结果：用Ang-（1-7）治疗导致IL-10，CD4+Foxp3+水平升高，Mres在肺和增强的巨噬细胞介导的细胞能力。此外，在用Ang-（1-7）治疗然后进行二次OVA攻击的过敏小鼠中，炎症也减少了。同样，在暴露于LPS的小鼠中，Ang-(1-7)有效预防肺部炎症。
结论：单剂量Ang-(1-7)可缓解肺部炎症并保护肺部免受随后的炎症攻击，突出了其对哮喘患者的潜在治疗作用。
方法：小鼠，致敏和攻击卵清蛋白（OVA），在嗜酸性粒细胞炎症的高峰期接受单一剂量的Ang-（1-7），最终OVA挑战后24小时。随后，小鼠在OVA攻击后48、72、96和120小时安乐死，细胞浸润，炎症介质，肺组织病理学,和巨噬细胞介导的白细胞活性进行了评估。在最后一次OVA攻击后120小时给予继发性炎症刺激（OVA或LPS），随后进行炎症分析.
结果：用Ang-（1-7）治疗导致IL-10，CD4+Foxp3+水平升高，Mres在肺和增强的巨噬细胞介导的细胞能力。此外，在用Ang-（1-7）治疗然后进行二次OVA攻击的过敏小鼠中，炎症也减少了。同样，在暴露于LPS的小鼠中，Ang-(1-7)有效预防肺部炎症。
结论：单剂量Ang-(1-7)可缓解肺部炎症并保护肺部免受随后的炎症攻击，突出了其对哮喘患者的潜在治疗作用。
