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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 哮喘是影响5-10％人口的气道的过敏性炎症。我们实验室和其他人的研究揭示了Th2细胞和细胞因子在诱导这些后期事件中的关键作用。但是，关于之前的“启动事件”知之甚少，有助于诱导后期响应。我们以前已经表明，花粉具有NADPH氧化酶活性，可以在NADPH存在下迅速产生超氧化物。 在这里，我们提出与花粉相关的NADPH氧化酶活性在晚期表型的启动中起着至关重要的作用。我们将检验假说，即1）花粉NADPH氧化酶增加了抗原过敏性敏化和抗原引起的后期AHR，粘蛋白AHR，粘蛋白和TH2过敏性炎症。 2）RWE的促氧化活性增强了特应患者的立即产生ROS的产生和晚期症状和Th2过敏性炎症。还将研究分子机制。将招募患有过敏性鼻炎症状和浅毛皮肤刺测试的人类受试者，以研究特定的目标2。将收集预定时间点滤纸和鼻洗样品。患有晚期症状的患者将被要求参与研究的第二阶段，以确定N-乙酰基半胱氨酸（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引起的氧化应激在过敏性疾病的发病机理中的作用。