Smoke induced changes in epithelial cell gene expression: development of an in vitro model for COPD

Abstract

Chronic obstructive pulmonary disease (COPD) includes emphysema and chronic bronchitis, which are characterised by a progressive airflow limitation and chronic inflammation. The pathogenesis of COPD involves different cells, mainly epithelial cells, macrophages, neutrophils, and CD8 lymphocytes. Bronchial epithelium lines the mucosal surface of the airways, forming a mechanical barrier that separates the external environment from the internal milieu. Recently, substantial evidence has emerged indicating that airway epithelial cells are able to liberate a number of chemokines fundamental to both inflammatory and immune responses. Therefore, we established an in vitro model by showing that cigarette smoke is able to induce the release of chemokines by lung epithelial cells. Furthermore, we show that cigarette smoke induced chemokine expression is resistant to dexamethasone, mimicking the clinical situation. In contrast, pyrrolidinedithiocarbamic acid, an experimental antioxidant compound, inhibited smoke induced chemokine expression. These results suggest that this epithelial cell culture model may allow the evaluation of novel anti-inflammatory compounds for the treatment of COPD directly on the relevant target cells in vitro. This approach may result in the replacement of animal experimentation in screening of new therapeutics for COPD.