Inflammation ( IF 4.5 ) Pub Date : 2021-04-16 , DOI: 10.1007/s10753-021-01466-3 Baowei Ma 1 , Seyyed Shamsadin Athari 2 , Entezar Mehrabi Nasab 3 , Limin Zhao 4
|
Abstract
Asthma is an inflammatory airway disease wherein bronchoconstriction, airway inflammation, and airway obstruction during asthma attacks are the main problems. It is recognized that imbalance of Th1/Th2 and Th17/Treg is a critical factor in asthma pathogenesis. Manipulation of these with signaling molecules such as mTOR, PI3K, Akt, and MyD88 can control asthma. Mouse model of allergic asthma was produced and treated with ketamine, metformin, metformin and ketamine, triciribine, LY294002, and torin2. MCh challenge test, BALf's Eos Count, the IL-4, 5, INF-γ, eicosanoid, total IgE levels were determined. The MUC5a, Foxp3, RORγt, PI3K, mTOR, Akt, PU.1, and MyD88 gene expressions and histopathology study were done. Asthma groups that were treated with all six components had reduced Penh value, total IgE, IL-4 and IL-5 levels, MUC5a, RORγt, MyD88 and mTOR expression, goblet cell hyperplasia, and mucus hyper-secretion. The eosinophil percentage and Cys-LT level were decreased by metformin and ketamine, triciribine, LY294002, and torin2. The level of IFN-γ was increased in triciribine, LY294002, and torin2. Metformin, metformin and ketamine, triciribine, LY294002, and torin2 reduced Akt and PI3K expression, peribronchial and perivascular inflammation, and increased expression of Foxp3. Torin2 had an effect on PU.1 expression. Inhibition of PI3K/AKT/mTOR and TLR4/MyD88/NF-κB signaling with targeted molecules can attenuate asthma pathology and play an important role in airways protection.
Graphical Abstract
中文翻译：
PI3K/AKT/mTOR 和 TLR4/MyD88/NF-κB 信号抑制剂减弱过敏性哮喘的病理机制
摘要
哮喘是一种炎症性气道疾病，主要问题是哮喘发作期间的支气管收缩、气道炎症和气道阻塞。Th1/Th2和Th17/Treg失衡是哮喘发病的关键因素。用 mTOR、PI3K、Akt 和 MyD88 等信号分子对这些进行操作可以控制哮喘。用氯胺酮、二甲双胍、二甲双胍和氯胺酮、曲西立滨、LY294002 和 torin2 制作和治疗过敏性哮喘小鼠模型。测定 MCh 激发试验、BALf 的 Eos 计数、IL-4、5、INF-γ、类花生酸、总 IgE 水平。进行了 MUC5a、Foxp3、RORγt、PI3K、mTOR、Akt、PU.1 和 MyD88 基因表达和组织病理学研究。用所有六种成分治疗的哮喘组的 Penh 值、总 IgE、IL-4 和 IL-5 水平、MUC5a、RORγt、MyD88 和 mTOR 表达、杯状细胞增生和粘液过度分泌。二甲双胍和氯胺酮、曲西立滨、LY294002 和 torin2 降低了嗜酸性粒细胞百分比和 Cys-LT 水平。triciribine、LY294002 和 torin2 的 IFN-γ 水平升高。二甲双胍、二甲双胍和氯胺酮、曲西立宾、LY294002 和 torin2 可降低 Akt 和 PI3K 表达、支气管周围和血管周围炎症，并增加 Foxp3 的表达。Torin2 对 PU.1 表达有影响。用靶向分子抑制 PI3K/AKT/mTOR 和 TLR4/MyD88/NF-κB 信号传导可以减轻哮喘病理并在气道保护中发挥重要作用。triciribine、LY294002 和 torin2 的 IFN-γ 水平升高。二甲双胍、二甲双胍和氯胺酮、曲西立宾、LY294002 和 torin2 可降低 Akt 和 PI3K 表达、支气管周围和血管周围炎症，并增加 Foxp3 的表达。Torin2 对 PU.1 表达有影响。用靶向分子抑制 PI3K/AKT/mTOR 和 TLR4/MyD88/NF-κB 信号传导可以减轻哮喘病理并在气道保护中发挥重要作用。triciribine、LY294002 和 torin2 的 IFN-γ 水平升高。二甲双胍、二甲双胍和氯胺酮、曲西立宾、LY294002 和 torin2 可降低 Akt 和 PI3K 表达、支气管周围和血管周围炎症，并增加 Foxp3 的表达。Torin2 对 PU.1 表达有影响。用靶向分子抑制 PI3K/AKT/mTOR 和 TLR4/MyD88/NF-κB 信号传导可以减轻哮喘病理并在气道保护中发挥重要作用。
京公网安备 11010802027423号