The Heme-oxygenase 1 (HO-1) as modulator of Cystic Fibrosis lung disease

In Cystic Fibrosis (CF)-affected lungs the primary defect is the salt and water imbalance across the cells that line the airway, which impair mucus clearance. This imbalance leads to the perturbation of important cellular mechanisms (such accumulation of oxidants and of cells belonging to the immune system), which will contribute to lung environmental changes. It is believed that these changes may favor the deleterious chronic bacterial colonization in the lung of CF-affected individuals. We have discovered that an important protective cellular response (heme-oxygenase-1/carbon monoxide) that normally is increased in non-CF lungs exposed to bacteria, virus and other stressor, is inefficiently induced in the lungs of CF patients as a consequence of defective CFTR function. In this proposal we aim to investigate the correlation between this dysfunction and CF lung disease, and whether restoration of this protective response may ameliorate CF lung disease. We will also test whether drugs that are already in use for other diseases (therefore safe to use on patients) and that are known to stimulate this protective response, can ameliorate CF dysfunctions on pre-clinical models for CF. At the end of this study, we will understand whether modulation of this protective response can be considered a potential therapeutic intervention for CF patients.