REV-ERBα主激素SR10067减弱了人类支气管上皮细胞中的Th2细胞因子介导的屏障功能障碍
Santhosh Kumar Duraisamy1, Isaac Kirubakaran Sundar1
1Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, U.S.A.
Clinical science (London, England : 1979)
|September 2, 2024
概括
REV-ERBα激活保护了对Th2细胞因子诱导的呼吸道上皮质屏障功能障碍. 这一发现表明REV-ERBα激活是喘等过敏性炎症性肺部疾病的潜在治疗策略.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 呼吸系统医学 呼吸系统医学
背景情况:
- 过敏原和Th2细胞因子破坏了呼吸道上皮质屏障的功能,增加了粘液的产生.
- 表皮屏障的完整性对于防止过敏原进入和炎症至关重要.
- 调节屏障功能的生理时钟机制是过敏肺部疾病的新兴治疗点.
研究的目的:
- 调查REV-ERBα激活是否可以保护人类支气管上皮细胞免受Th2细胞因子诱导的屏障功能障碍.
- 在过敏炎症的背景下探索REV-ERBα在维持上皮屏障完整性的作用.
主要方法:
- 人类支气管上皮细胞用Th2细胞因子或室内灰尘虫 (HDM) 提取物进行治疗.
- 测量了体电阻 (TEER),以评估屏障功能.
- 分析了附着结合复合体 (AJC) 和紧密结合 (TJ) 蛋白质的局部.
- 量化了上皮屏障的mRNA和蛋白质水平以及昼夜钟目标.
主要成果:
- Th2细胞因子和HDM显著降低了细胞阻抗和TEER,表明屏障功能障碍.
- 使用SR10067 (REV-ERBα激活剂) 的预治疗减弱了Th2细胞因子诱导的屏障功能障碍.
- SR10067改善了TEER,降低了透性,并恢复了AJC和TJ蛋白的局部化.
- REV-ERBα激活使关键的上皮屏障和昼夜钟基因的mRNA和蛋白质水平正常化.
结论:
- REV-ERBα激活有效地保护人类支气管上皮细胞的Th2细胞因子诱导的上皮屏障功能障碍.
- 这项研究表明REV-ERBα在调节上皮质屏障功能的新作用.
- REV-ERBα激活作为喘和其他过敏呼吸道疾病的治疗策略具有前景.
相关概念视频
01:25Antiasthma Drugs: β2-Adrenoceptor Agonists
239
Bronchodilators are critical in managing asthma, a chronic respiratory condition characterized by airway constriction due to inflammation and hyper-reactivity. Specifically, bronchodilators ease this constriction by relaxing the bronchial muscles, facilitating easier breathing.
One class of bronchodilators includes β2-adrenoceptor agonists. These agents target the β2-adrenoceptors located on bronchial smooth muscle cells. By stimulating these receptors, β2-agonists induce...
One class of bronchodilators includes β2-adrenoceptor agonists. These agents target the β2-adrenoceptors located on bronchial smooth muscle cells. By stimulating these receptors, β2-agonists induce...
239
01:19Antiasthma Drugs: Leukotriene Modifiers
253
Leukotriene modifiers, or cysteinyl leukotriene receptor antagonists, are medications used to manage chronic asthma. These agents target specific inflammatory mediators produced during arachidonic acid metabolism, an essential process in generating inflammation in the body.
Leukotriene modifiers work through two distinct mechanisms:
Leukotriene modifiers work through two distinct mechanisms:
253
01:20Asthma: Pathogenesis and Management
374
Asthma is a chronic pulmonary condition involving inflammation of the airways, hyper-reactivity, and reversible obstruction of the airways. This condition can significantly impact a person's quality of life, making breathing difficult and leading to distressing symptoms.
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
Asthma is classified as allergic and non-allergic. Allergens such as dust mites, pollen, and pet dander trigger allergic asthma, while factors like cold air, intense emotions, or exercise can induce non-allergic asthma.
374
01:17Drugs Used in Lower Respiratory Disorders: Overview
362
Lower respiratory tract disorders present challenges that often require skilled and nuanced approaches for effective management. Common ailments, such as asthma and chronic obstructive pulmonary disease (COPD), have prompted the development of intricate treatment strategies involving bronchodilators and anti-inflammatory drugs, each tailored to ease breathing and revitalize the lungs.
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...
Bronchodilators, the first step of respiration enhancement, come in various forms, each with its own mechanism...
362
01:25Antiasthma Drugs: Mast Cell Stabilizers and Anti-IgE Drugs
251
Asthma is a chronic respiratory condition for which new therapeutic avenues, including anti-inflammatory drugs like mast cell stabilizers and anti-IgE treatments, continue to be developed.
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
Mast cell stabilizers, such as cromolyn (also known as sodium cromoglycate) and nedocromil (Tilade), are effective drugs in asthma management. These stabilizers hinder histamine release by skillfully obstructing the activation of mast cells and other cellular entities. Notably, they navigate this task without...
251
01:26Asthma-II: Pathophysiology and Classification
2.6K
Asthma is a prevalent chronic respiratory condition marked by inflammation and hyperresponsiveness of the airways. Its pathophysiology involves complex interactions among inflammatory pathways, immune responses, and neural mechanisms.
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
Additionally, environmental and genetic factors play crucial roles in determining an individual's susceptibility to asthma and the severity of their condition.
Critical processes in asthma pathophysiology include:
2.6K