Beta 2-agonist-elevated stress response in human bronchial epithelial cells in vivo and in vitro

Recent studies report high baseline levels of stress (heat shock) proteins in bronchial epithelial cells from asthmatic individuals. The promoter of the gene encoding the 72-kDa heat shock protein has an element responsive to cAMP, which may be affected by beta-agonists. This study examined stress protein levels in subjects enrolled in a segmental lung allergen challenge study to determine whether beta-agonist medication could contribute to a stress response. Subjects were divided on the basis of no premedication (n = 17), metered dose inhalations of albuterol (n = 24), or placebo inhalation (n = 3) prior to bronchoscopy. Levels of the inducible stress protein Hsp72 and constitutive Hsp73 were quantitated in bronchial epithelial cells from brush biopsy of allergic nonasthmatic, allergic asthmatic, and normal individuals. Mean levels were increased significantly (p < 0.003 and p < 0.004, respectively) in those subjects who received albuterol premedication. No significant differences were found between clinical groups of individuals or for placebo inhalation vs nonpremedication. Albuterol in vitro increased the levels of Hsp72 and Hsp73 in epithelial cells from either nonpremedicated or placebo-treated donors; the Hsp72 levels correlated linearly with increased albuterol concentration (r = 0.81, p < 0.01). Therefore, beta-agonists elevate or prolong an elevated stress response in epithelial cells, possibly through cAMP-mediated effects.