beta2-agonists promote host defense against bacterial infection in primary human bronchial epithelial cells.
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.
Gross
Claire A
CA
Department of Medicine, National Jewish Health, 1400 Jackson Street, Denver, Colorado 80206, USA.
Bowler
Russell P
RP
Green
Rebecca M
RM
Weinberger
Andrew R
AR
Schnell
Christina
C
Chu
Hong Wei
HW
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
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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