OXIDATIVE STRESS IN ASTHMA INITIATION

哮喘发作中的氧化应激

• 批准号: 7952179
• 负责人: SANJIV SUR
• 金额: $ 0.19万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-01 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7952179
• 关键词: Acetylcysteine; Affect; Allergic; Allergic rhinitis; Ambrosia; Antigens; Asthma; Attenuated; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Disease; Event; Funding; Grant; Inflammation; Institution; Molecular; Mucins; Mus; NADP; NADPH Oxidase; Nasal Lavage Fluid; Oxidative Stress; Paper; Pathogenesis; Patients; Phase; Phase II Clinical Trials; Play; Pollen; Population; Production; Reactive Oxygen Species; Recruitment Activity; Research; Research Personnel; Resources; Role; Sampling; Skin; Source; Superoxides; Symptoms; Testing; Th2 Cells; Time; United States National Institutes of Health; allergic airway inflammation; cytokine; human subject; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Asthma is an allergic inflammation of the airways affecting 5-10% of the population. Studies from our lab and others have revealed a critical role of Th2 cells and cytokines in the induction of these late phase events. However, very little is known about the 'initiation events' that precede and contribute to the induction of late phase response. We have previously shown that pollens possess NADPH oxidase activity that can rapidly generate superoxide in the presence of NADPH. Here we propose that pollen-associated NADPH oxidase activity plays a critical role in the initiation of the late phase phenotype.We will test the hypothesis that- 1) pollen NADPH oxidases augment allergic sensitization and antigen-induced late phase AHR, mucin production and Th2 allergic inflammation in mice. 2) pro-oxidant activity of RWE augments immediate ROS production and late phase symptoms and Th2 allergic inflammation in atopic patients. Molecular mechanisms will also be studied. Human subjects with symptoms of allergic rhinitis and a positive ragweed skin prick test will be recruited to study specific aim 2. At predetermined time points filter paper and nasal wash samples will be collected. Patients who have late phase symptoms will be asked to participate in phase II of the study to determine whether scavenging reactive oxygen species by N-acetyl cysteine (NAC) can attenuate the late phase symptoms. Information obtained from this proposal will help understand the role of pollen-induced oxidative stress in the pathogenesis of allergic diseases.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 哮喘是一种气道过敏性炎症，影响 5-10% 的人口。我们实验室和其他实验室的研究揭示了 Th2 细胞和细胞因子在诱导这些晚期事件中的关键作用。然而，人们对晚相反应之前和有助于诱导晚相反应的“起始事件”知之甚少。我们之前已经证明花粉具有 NADPH 氧化酶活性，在 NADPH 存在的情况下可以快速产生超氧化物。 在这里，我们提出花粉相关的 NADPH 氧化酶活性在晚期表型的启动中起着关键作用。我们将检验以下假设：1) 花粉 NADPH 氧化酶增强小鼠的过敏致敏和抗原诱导的晚期 AHR、粘蛋白产生和 Th2 过敏性炎症。 2) RWE 的促氧化活性可增强特应性患者的即时 ROS 产生、晚期症状和 Th2 过敏性炎症。分子机制也将被研究。将招募具有过敏性鼻炎症状且豚草皮肤点刺试验呈阳性的人类受试者来研究特定目标2。在预定时间点将收集滤纸和鼻洗样本。有晚期症状的患者将被要求参加第二阶段的研究，以确定通过 N-乙酰半胱氨酸 (NAC) 清除活性氧是否可以减轻晚期症状。从该提案中获得的信息将有助于了解花粉诱导的氧化应激在过敏性疾病发病机制中的作用。