Inhibition of ozone-induced lung neutrophilia and nuclear factor-kappaB binding activity by vitamin A in rat.
Vitamin A binds to retinoic acid receptors, which in turn may interact with other transcription factors. We determined its effect (2500 and 5000 IU/kg) on nuclear factor-kappaB binding activity in the lung, airway inflammation and bronchial hyperresponsiveness in rats exposed to ozone. Ozone (3 ppm, 3 h) caused neutrophil influx into bronchoalveolar lavage fluid (16.2+/-0.8 x 10(5) cells/ml, p < 0.01) and bronchial hyperresponsiveness (-logPC200ACh = 2.54+/-0.19, p < 0.05, compared to control animals, respectively). Vitamin A inhibited this neutrophilia dose-dependently together with the increased DNA-binding activity of nuclear factor-KB in lung extracts. Vitamin A did not affect bronchial hyperresponsiveness at both doses. Vitamin A inhibits ozone-induced neutrophilic inflammation through a reduction in nuclear factor-kappaB DNA binding activity.
Hisada
T
T
Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, UK.
Adcock
I M
IM
Nasuhara
Y
Y
Salmon
M
M
Huang
T J
TJ
Barnes
P J
PJ
Chung
K F
KF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016535:Bronchial Hyperreactivity / Q000139:chemically induced; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000473:pathology; D010083:Oxidants, Photochemical / Q000009:adverse effects*; D010126:Ozone / Q000009:adverse effects*; D011485:Protein Binding; D051381:Rats; D011914:Rats, Inbred BN; D014665:Vasodilator Agents / Q000494:pharmacology; D014801:Vitamin A / Q000494:pharmacology*
D004268:DNA-Binding Proteins; D016328:NF-kappa B; D010083:Oxidants, Photochemical; D014665:Vasodilator Agents; D014801:Vitamin A; D010126:Ozone; D000109:Acetylcholine