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Einfluss der Vitamin D - Cathelizidin Achse auf die Entwicklung des Lungenemphysems

维生素D-导管素轴对肺气肿发生的影响

基本信息

批准号：
159893328
负责人：
Professor Dr. Robert Bals
金额：
--
依托单位：
Klinik für Innere Medizin V - Pneumologie, Allergologie, Beatmungs- und Umweltmedizin
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2009
资助国家：
德国
起止时间：
2008-12-31 至 2013-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/159893328?language=en
关键词：
Einfluss der Vitamin Cathelizidin Achse

项目摘要

Chronic obstructive pulmonary disease (COPD) includes emphysema development of the lung parenchyma and chronic inflammation of the airways. Recent data have helped to further understand the underlying mechanisms. Emphysema development is likely multifactorial with fastened senescence and decreased repair as important components. Bronchitis involves the activation of innate and adaptive immune functions. Cathelicidin (CATH) antimicrobial peptides are effector molecules of innate immunity with various regulatory activities. Studies from our laboratory and others showed that CATH induces repair of epithelial cells and induces angiogenesis. CATH also modulates inflammatory immune reactions. These data led us to hypothesize that CATH has a role in protection from smoke-induced COPD. Preliminary data showed that CATH is capable to induce alveolar and bronchiolar repair and to decrease the deleterious effect of smoke/elastase induced lung damage. Further data show that the induction of CATH by vitamin D is important. The aim of this project is to proof that the axis vitamin D-CATH is important in the homeostastic response of the lung to smoke-induced damage. We aim to show that vitamin D induces epithelial and macrophage CATH and that smoke inhibits this process. CATH is critical to control bronchiolar inflammation during smoke exposure and critical to regulate repair after lung damage. We will apply tissue culture models to study mechanisms and animal models to validate mechanisms in vivo. In the further run, translational studies will test whether these mechanisms are relevant for COPD patients. This projects aims to identify a mechanism that protects against smoke-induced lung damage and thus potentially offers the perspective of therapeutic development.

慢性阻塞性肺疾病（COPD）包括肺实质的肺气肿和气道的慢性炎症。最近的数据有助于进一步了解潜在的机制。肺气肿的发展可能是多因素的，其中衰老加速和修复减少是重要组成部分。支气管炎涉及先天性和适应性免疫功能的激活。导管素（CATH）抗菌肽是先天免疫的效应分子，具有多种调节活性。我们实验室和其他实验室的研究表明，CATH 诱导上皮细胞修复并诱导血管生成。 CATH 还调节炎症免疫反应。这些数据使我们推测 CATH 在预防烟雾诱发的慢性阻塞性肺病方面发挥着作用。初步数据表明，CATH 能够诱导肺泡和细支气管修复，并减少烟雾/弹性蛋白酶引起的肺损伤的有害影响。进一步的数据表明，维生素 D 诱导 CATH 很重要。该项目的目的是证明维生素 D-CATH 轴对于肺部对烟雾引起的损伤的稳态反应非常重要。我们的目的是证明维生素 D 会诱导上皮细胞和巨噬细胞 CATH，而烟雾会抑制这一过程。 CATH 对于控制烟雾暴露期间的细支气管炎症至关重要，对于调节肺损伤后的修复也至关重要。我们将应用组织培养模型来研究机制，并应用动物模型来验证体内机制。下一步，转化研究将测试这些机制是否与慢性阻塞性肺病患者相关。该项目旨在确定一种防止烟雾引起的肺损伤的机制，从而为治疗开发提供潜在的前景。