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Cholinergic anti-inflammatory pathway confers airway protection against oxidative damage and attenuates inflammation in an allergic asthma model.

胆碱能抗炎通路赋予气道抗氧化损伤保护作用,减轻过敏性哮喘模型的炎症。

  • 影响因子:3.89
  • DOI:10.1002/jcp.29101
  • 作者列表:"Antunes GL","Silveira JS","Kaiber DB","Luft C","da Costa MS","Marques EP","Ferreira FS","Breda RV","Wyse ATS","Stein RT","Pitrez PM","da Cunha AA
  • 发表时间:2020-02-01
Abstract

:Asthma is characterized by the influx of inflammatory cells, especially of eosinophils as well as reactive oxygen species (ROS) production, driven by the release of the T helper 2 (Th2)-cell-associated cytokines. The cholinergic anti-inflammatory pathway (CAP) inhibit cytokines production and controls inflammation. Thus, we investigated the effects of pharmacological activation of CAP by neostigmine on oxidative stress and airway inflammation in an allergic asthma model. After the OVA challenge, mice were treated with neostigmine. We showed that CAP activation by neostigmine reduced the levels of pro-inflammatory cytokines (IL-4, IL-5, IL-13, IL-1β, and TNF-α), which resulted in a decrease of eosinophils influx. Furthermore, neostigmine also conferred airway protection against oxidative stress, attenuating ROS production through the increase of antioxidant defense, evidenced by the catalase (CAT) activity. We propose, for the first time, that pharmacological activation of the CAP can lead to new possibilities in the therapeutic management of allergic asthma.

摘要

: 哮喘的特征是炎症细胞的流入,特别是嗜酸性粒细胞以及活性氧 (ROS) 的产生,由辅助性 T 细胞 2 (Th2) 的释放驱动 -细胞相关细胞因子。胆碱能抗炎通路 (CAP) 抑制细胞因子的产生并控制炎症。因此,我们在过敏性哮喘模型中研究了新斯的明药理激活 CAP 对氧化应激和气道炎症的影响。OVA 激发后,小鼠用新斯的明治疗。我们发现新斯的明激活 CAP 可降低促炎细胞因子 (IL-4 、 IL-5 、 IL-13 、 il-1 β 和 TNF-α) 的水平,从而导致嗜酸性粒细胞内流减少。此外,新斯的明还赋予气道对氧化应激的保护作用,通过抗氧化防御的增加减弱 ROS 的产生,过氧化氢酶 (CAT) 活性证明了这一点。我们首次提出,CAP 的药理学激活可以为过敏性哮喘的治疗管理带来新的可能性。

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DOI:10.1042/BST20191010
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