Effects of inhaled beta agonist and corticosteroid treatment on nuclear transcription factors in bronchial mucosa in asthma.
BACKGROUND
Inhaled corticosteroids and beta agonists are the most commonly used treatments in asthma and are often used together. Recent evidence suggests that many of the anti-inflammatory actions of corticosteroids are mediated by cross-talk between the activated glucocorticoid receptor (GR) and other transcription factors such as the pro-inflammatory nuclear factor kappa B (NFkappaB). Beta agonists can activate the transcription factor cAMP response element binding protein (CREB). A mutual inhibition between GR and CREB occurs in vitro which raises the possibility of a negative interaction between corticosteroid and beta agonist drugs. A study was undertaken to determine whether these interactions occur during treatment with beta2 agonists and corticosteroids in asthma.


METHODS
Seven subjects who were participating in a randomised, placebo controlled, crossover study of six weeks treatment with inhaled budesonide (400 microg twice daily), terbutaline (1 mg four times daily), and combined treatment were recruited. Biopsy samples of the bronchial mucosa were obtained after each treatment and analysed for the DNA binding activity of GR, CREB, and NFkappaB.


RESULTS
Budesonide increased GR activity (p<0.05) and decreased NFkappaB activity (p<0.05). No treatment combination altered CREB activity and terbutaline had no significant effects on any transcription factor.


CONCLUSIONS
Inhaled corticosteroids have significant effects on GR and NFkappaB activity in bronchial mucosa. A negative interaction between inhaled corticosteroids and beta agonists was not found.
Hancox
R J
RJ
Department of Respiratory Medicine, Dunedin School of Medicine, University of Otago, New Zealand.
Stevens
D A
DA
Adcock
I M
IM
Barnes
P J
PJ
Taylor
D R
DR
D000280:Administration, Inhalation; D000293:Adolescent; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D001980:Bronchi / Q000187:drug effects; D019819:Budesonide / Q000008:administration & dosage*; D018592:Cross-Over Studies; D017362:Cyclic AMP Response Element-Binding Protein / Q000187:drug effects / Q000378:metabolism; D004347:Drug Interactions; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000187:drug effects / Q000378:metabolism; D020545:Respiratory Mucosa; D013726:Terbutaline / Q000008:administration & dosage*; D014157:Transcription Factors / Q000187:drug effects* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D017362:Cyclic AMP Response Element-Binding Protein; D016328:NF-kappa B; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; D019819:Budesonide; D013726:Terbutaline