P08 - Role of TRPML1 in chronic toxic lung disease
Toxicants in cigarette smoke or inhalation of environmental and occupational pollutants such as metals in asbestosis or silicosis, high levels of dust in coal mining and certain gases, medications such as amiodarone, the chemotherapy drugs bleomycin, busulfan, and methotrexate, or the antibiotic nitrofurantoin, but also acute and chronic infections can cause severe, long lasting or permanent lung injury, resulting in diseases such as COPD, emphysema or lung fibrosis.
Currently, there are no drugs available that can reduce mortality due to these diseases and hence, there is an urgent need for novel and innovative therapeutic strategies and targets. Chronic inflammation mediated e.g. by macrophages is a central component of these lung diseases. Endolysosomal cation channels, in particular TRPML channels (TRPML1, TRPML2, TRPML3) and two-pore channels (TPC1, TPC2) have been shown recently to be highly expressed in macrophages but also other immune cells and have been postulated to control intracellular vesicle trafficking and endolysosomal exocytosis, and to play critical roles in endocytosis and phagocytosis. The relevance of these channels for the development of emphysema, COPD, or lung fibrosis shall be assessed in detail in this project.