title: beta2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells.
abstract: BACKGROUND
  Airway epithelial cells are critical in host defense against bacteria including Mycoplasma pneumoniae (Mp) in chronic obstructive pulmonary disease (COPD) and asthma. beta2-agonists are mainstay of COPD and asthma therapy, but whether beta2-agonists directly affect airway epithelial host defense functions is unclear.
  
  
  METHODS
  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 beta2-agonists albuterol and formoterol for up to seven days. Mp and host defense proteins short palate, lung, and nasal epithelial clone 1 (SPLUNC1) and beta-defensin-2 were quantified. Expression of beta2-adrenergic receptors was also measured by real-time quantitative RT-PCR.
  
  
  RESULTS
  (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 beta-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 beta2-adrenergic receptors.
  
  
  CONCLUSIONS
  These results for the first time show that beta2-agonists enhance host defense functions of primary bronchial epithelial cells from normal and asthma subjects, which is attenuated by IL-13.
authors.affiliation: Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA.
authors.forename: Claire A
authors.initials: CA
authors.lastname: Gross
authors.forename: Russell P
authors.initials: RP
authors.lastname: Bowler
authors.forename: Rebecca M
authors.initials: RM
authors.lastname: Green
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Weinberger
authors.forename: Christina
authors.initials: C
authors.lastname: Schnell
authors.forename: Hong Wei
authors.initials: HW
authors.lastname: Chu
mesh_terms: D000322:Adrenergic Agonists / Q000494:pharmacology*; D058666:Adrenergic beta-2 Receptor Agonists; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D001424:Bacterial Infections / Q000276:immunology*; D001980:Bronchi / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D002478:Cells, Cultured; D004983:Ethanolamines / Q000494:pharmacology; D005260:Female; D000068759:Formoterol Fumarate; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D018793:Interleukin-13 / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D009177:Mycoplasma pneumoniae / Q000187:drug effects / Q000276:immunology; D010750:Phosphoproteins / Q000378:metabolism; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D012906:Smoke / Q000009:adverse effects; D023083:beta-Defensins / Q000378:metabolism
chemical_list: D000322:Adrenergic Agonists; D058666:Adrenergic beta-2 Receptor Agonists; C485599:BPIFA1 protein, human; C106641:DEFB4A protein, human; D004983:Ethanolamines; D006023:Glycoproteins; D018793:Interleukin-13; D010750:Phosphoproteins; D018343:Receptors, Adrenergic, beta-2; D012906:Smoke; D023083:beta-Defensins; D000420:Albuterol; D000068759:Formoterol Fumarate
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