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

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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.