β2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells
- Equal contributors
1 Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado, 80206, USA
2 University of Colorado-Denver, 12800 E. 19th Avenue, Aurora, Colorado, 80045, USA
BMC Pulmonary Medicine 2010, 10:30 doi:10.1186/1471-2466-10-30Published: 14 May 2010
Airway epithelial cells are critical in host defense against bacteria including Mycoplasma pneumoniae (Mp) in chronic obstructive pulmonary disease (COPD) and asthma. β2-agonists are mainstay of COPD and asthma therapy, but whether β2-agonists directly affect airway epithelial host defense functions is unclear.
Epithelial cells from bronchial brushings of normal (n = 8), asthma (n = 8) and COPD (n = 8) subjects were grown in air-liquid interface cultures, and treated with cigarette smoke extract (CSE) and/or Th2 cytokine IL-13, followed by Mp infection and treatment with β2-agonists albuterol and formoterol for up to seven days. Mp and host defense proteins short palate, lung, and nasal epithelial clone 1 (SPLUNC1) and β-defensin-2 were quantified. Expression of β2-adrenergic receptors was also measured by real-time quantitative RT-PCR.
(R)- or racemic albuterol and (R,R)- or racemic formoterol significantly decreased Mp levels in normal and asthma epithelial cells. Normal cells treated with Mp and (R)- or racemic albuterol showed an increase in SPLUNC1, but not in β-defensin-2. COPD cells did not respond to drug treatment with a significant decrease in Mp or an increase in SPLUNC1. IL-13 attenuated drug effects on Mp, and markedly decreased SPLUNC1 and β2-adrenergic receptors.
These results for the first time show that β2-agonists enhance host defense functions of primary bronchial epithelial cells from normal and asthma subjects, which is attenuated by IL-13.