Effects of maresin-1 & organic dust on lung inflammation

maresin-1 的作用

基本信息

批准号：
8649764
负责人：
Tara M Nordgren
金额：
$ 5.45万
依托单位：
UNIVERSITY OF NEBRASKA MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-02-01 至 2016-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8649764
关键词：
Acute Agricultural Workers Agriculture Air Pollutants Anti-Inflammatory Agents Anti-inflammatory Attenuated Cause of Death Cell Adhesion Molecules Cellular Infiltration Chronic Chronic Obstructive Airway Disease Data Diesel Exhaust Diet Disease Dose Dust Employee Strikes Environmental Exposure Epithelial Cells Exposure to Foundations Goals Health Benefit In Vitro Inflammation Inflammatory Inflammatory Response Intercellular adhesion molecule 1 Investigation Knowledge Lead Lung Lung Inflammation Lung Lavage Fluid Mediator of activation protein Mission Modeling Mus National Institute of Environmental Health Sciences Occupational Exposure Omega-3 Fatty Acids Pilot Projects Process Property Public Health Recruitment Activity Research Role Scheme Serum Response Factor Signal Transduction Slice Testing Therapeutic Tobacco smoke Treatment Protocols United States Work airway epithelium airway inflammation career combat cytokine improved in vivo lipid mediator macrophage neutrophil novel pre-clinical prevent public health relevance research study response

项目摘要

DESCRIPTION (provided by applicant): Chronic obstructive pulmonary disease (COPD) is the third leading cause of death in the United States and an estimated 15% of COPD cases are related to occupational exposures. In agricultural workers, organic dust exposures lead to damaging acute and chronic airway inflammation, and existing therapeutics do not adequately treat the resulting airway disease. Thus, novel preventative or treatment schemes are vitally needed to combat the deleterious inflammatory effects of these exposures. The health benefits of diets high in omega-3 fatty acids (?-3 FA) are well recognized, but incompletely understood. Recent studies reveal certain ?-3 FA derivatives attenuate and resolve inflammation. These "pro-resolving" mediators (PRM) may be key to the beneficial effects of ?-3 FA. Harnessing the anti-inflammatory and pro-resolving properties of PRM in preventative and treatment regimens could revolutionize the way we combat inflammatory disease processes. However, the potential for PRM in treating organic dust-related airway disease, as well as their effects on key airway inflammation initiators, the bronchial epithelial cells (BECs), have not yet been studied. Therefore, the objective for the proposed research is to determine the utility of a PRM, maresin-1 (MaR1), at limiting the inflammatory effects of organic dust exposures. It is hypothesized that MaR1 will reduce airway inflammation and increase the anti-inflammatory and pro-resolving actions of BECs during organic dust exposures. To test this hypothesis, two specific aims are proposed. Aim 1 will focus on delineating the effects of MaR1 on organic dust-induced airway inflammation in a preclinical murine model of single and repetitive exposures. Aim 2 will focus on establishing how MaR1 decreases the pro-inflammatory responses of BECs to organic dust by (a) determining what pro-inflammatory responses in dust extract-stimulated BECs are modified by MaR1, and (b) defining the mechanisms of MaR1-induced changes in dust extract-treated BECs. Taken together, the results of these aims are expected to have important positive impacts; they will demonstrate the utility of MaR1 in treating organic dust-induced airway disease, and expose the potential for PRM as primary or adjunct therapies in inflammatory airway diseases. These experiments are therefore of great translational significance, potentially transforming the way acute and chronic inflammatory airway diseases are prevented and treated.

描述（由申请人提供）：慢性阻塞性肺病 (COPD) 是美国第三大死因，估计 15% 的 COPD 病例与职业暴露有关。对于农业工人来说，有机粉尘暴露会导致破坏性的急性和慢性气道炎症，而现有的治疗方法不能充分治疗由此产生的气道疾病。因此，迫切需要新的预防或治疗方案来对抗这些暴露的有害炎症作用。富含 omega-3 脂肪酸 (?-3 FA) 的饮食对健康的益处已得到广泛认可，但尚未完全了解。最近的研究表明某些 β-3 FA 衍生物可以减轻和解决炎症。这些“促解决”介质 (PRM) 可能是 β-3 FA 有益作用的关键。在预防和治疗方案中利用 PRM 的抗炎和促消退特性可能会彻底改变我们对抗炎症性疾病过程的方式。然而，PRM 治疗有机粉尘相关气道疾病的潜力及其对关键气道炎症引发剂支气管上皮细胞 (BEC) 的影响尚未得到研究。因此，本研究的目的是确定 PRM maresin-1 (MaR1) 在限制有机粉尘暴露的炎症效应方面的效用。据推测，在有机粉尘暴露期间，MaR1 会减少气道炎症并增强 BEC 的抗炎和促消退作用。为了检验这一假设，提出了两个具体目标。目标 1 将重点描述 MaR1 在单次和重复暴露的临床前小鼠模型中对有机粉尘引起的气道炎症的影响。目标 2 将侧重于确定 MaR1 如何降低 BEC 对有机粉尘的促炎反应，方法是：(a) 确定 MaR1 可以改变粉尘提取物刺激的 BEC 中的哪些促炎反应，以及 (b) 定义 MaR1 的机制诱导灰尘提取物处理的 BEC 发生变化。总的来说，这些目标的结果预计将产生重要的积极影响；他们将展示 MaR1 在治疗有机粉尘引起的气道疾病中的效用，并揭示 PRM 作为炎症性气道疾病主要或辅助疗法的潜力。因此，这些实验具有重大的转化意义，有可能改变急性和慢性炎症性气道疾病的预防和治疗方式。