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

慢性阻塞性肺疾病（COPD）包括肺气肿、肺实质发展和气道慢性炎症。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，其中衰老加快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。Cathelicidin（CATH）抗菌肽是具有多种调节活性的天然免疫效应分子。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。这些数据使我们假设CATH在防止吸烟诱导的COPD中具有作用。初步数据显示，CATH能够诱导肺泡和细支气管修复，并降低烟雾/弹性蛋白酶诱导的肺损伤的有害作用。进一步的数据表明，维生素D诱导CATH是重要的。该项目的目的是证明轴维生素D-CATH在肺对吸烟引起的损伤的稳态反应中是重要的。我们的目的是表明，维生素D诱导上皮和巨噬细胞CATH和烟雾抑制这一过程。CATH对控制烟雾暴露期间的细支气管炎症至关重要，对调节肺损伤后的修复至关重要。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。在进一步的运行中，转化研究将测试这些机制是否与COPD患者相关。该项目旨在确定一种机制，防止吸烟引起的肺损伤，从而可能提供治疗发展的前景。

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.