Inflammatory Profiles of Asthma and COPD Primary Human Bronchial Epithelial Cells in Response to LPS and an Inflammatory Inhibitor



Branscome, Heather

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Chronic obstructive pulmonary disease (COPD) and asthma are two of the most common inflammatory diseases of the respiratory system. Collectively, they affect hundreds of millions of individuals worldwide and are associated with high levels of mortality. Treatment options are currently limited to the use of long-acting bronchodilators and glucocorticoid steroids, which act only to reduce symptoms rather than to reverse disease progression. While airway inflammation is a hallmark feature of asthma and COPD, there are inherent differences in the types of cells and molecular mechanisms involved. Previous research has highlighted the importance of the innate immune system in orchestrating the inflammatory response and unique inflammatory patterns have been identified for each of these diseases. The current thesis examined the inflammatory profiles of ATCC human primary bronchial epithelial cells (HBECs) obtained from a variety of normal and diseased donors. We have demonstrated by ELISA that these cell types can be activated by an exogenous stimulus (LPS) to produce increased levels of IL-8 cytokine when grown in two-dimensional culture. The relative gene expression of other critical pro-inflammatory cytokines such as IL-6 and TNF-α was also examined and found to be dysregulated after exposure to LPS. Taken together, these factors may contribute to disease pathogenesis. Lastly, the anti-inflammatory effects of a glucocorticoid steroid, budesonide, were evaluated in LPS-challenged cells. Budesonide was effective in reducing IL-8 cytokine levels in five out of the six cell types tested. Ongoing research will focus on repeating these studies in three-dimensional cultures to better recreate the conditions in vivo.



Bronchial epithelial cells, Chronic Obstructive Pulmonary Disease, Asthma, Budesonide