Stress Response in Chronic Obstructive Pulmonary Disease - Effect of Cigarette Smoke Extract and Hypoxia on Structural Lung Cells

Sammanfattning: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death worldwide according to the world health organization. It is a disease characterized by chronic inflammation and emphysema, and cigarette smoking is the main cause of COPD development. There are several forms of stress present in the lungs of COPD patients, such as smoking induced endoplasmic reticulum stress or hypoxic stress caused by pathological changes in the lung. Many of the mechanisms behind COPD are still unknown, such as why some people develop COPD while others do not despite similar smoking habits. We have investigated differences in how lung fibroblasts from healthy and COPD subjects react at the transcriptional level to cigarette smoke extract or hypoxic exposure. We have also stained the cells to visualize and measure stress related proteins. Additionally, two epithelial cell lines of alveolar or bronchial origin were investigated in a similar way. From these investigations, we have found that there is a difference in how COPD subjects respond to stress, compared to healthy subjects. The healthy subjects go through several changes in expression to try to solve the stress, while this response is lacking in subjects with COPD. This difference is especially noticeable in pathways relating to apoptosis and cell proliferation, but also in pathways relating to hypoxic and endoplasmic reticulum stress. Lung fibroblasts from healthy subjects go into senescence in response to the stress and if the cell fails to resolve the stress, it undergoes apoptosis. Lung fibroblasts from COPD subjects on the other hand regulate different pathways and go straight into apoptosis. This atypical and deficient response in COPD subjects could be a contributing factor to disease progression and to why some people develop the disease.