How does smoke activate mucin transcription in lung cells?
Initial Award Abstract Healthy human airways produce several milliliters of mucus per day. In contrast, the airways of smokers suffering from bronchitis produce several hundred. The presence of excessive mucus is deleterious in that it gives rise to airflow obstruction (i.e., blockage of the conducting airways in the lung), recurrent infection and cough. There is currently only indirect evidence that smoke leads to excessive mucus production and the mechanisms are not known. We recently observed that isolated lung cells in culture, when directly exposed to cigarette smoke, are stimulated to overproduce mucin, a glycoprotein that is the major component of mucus. This was a fortunate breakthrough since it meant that the biological pathway controlling mucin production (and thus the mucus increase associated with smoking) resides in airway lung cells and can therefore be studied in detail using cell culture models of pulmonary airways. We will perform experiments to determine the molecular
