Heme oxygenase-1 prevents airway mucus hypersecretion induced by cigarette smoke in rodents and humans.
We investigated the role of heme oxygenase-1 (HO-1), a powerful anti-inflammatory and anti-oxidant enzyme, in modulating cigarette smoke (CS)-induced mucus secretion. In both rats and mice, 5-day CS exposure increased HO-1 expression and activity, mucus secretion, MUCIN 5AC (MUC5AC) gene and protein expression, and local inflammation, along with up-regulation of dual oxidase 1 gene expression and both the activity and phosphorylation of the epidermal growth factor receptor, which is involved in MUC5AC induction. Pharmacological induction of HO-1 prevented these actions and inhibition of HO-1 expression by a specific siRNA potentiated them. In French participants to the European Community Respiratory Health Survey II (n = 210, 30 to 53 years of age, 50% males) exposed to CS, a significant increase in the percentage of participants with chronic sputum was observed in those harboring at least one allele with a long (GT)(n) in the HO-1 promoter gene (>33 repeats), which is associated with a low level of HO-1 protein expression, compared with those with a short number of (GT)n repeats (21.7% versus 8.6%, P = 0.047). No such results were observed in those who had never smoked (n = 297). We conclude that HO-1 has a significant protective effect against airway mucus hypersecretion in animals and humans exposed to CS.
Almolki
Abdelhamid
A
INSERM U700, Université Paris 7, Paris, France.
Guenegou
Armelle
A
Golda
Slawomir
S
Boyer
Laurent
L
Benallaoua
Mourad
M
Amara
Nadia
N
Bachoual
Rafik
R
Martin
Clémence
C
Rannou
François
F
Lanone
Sophie
S
Dulak
Jozef
J
Burgel
Pierre-Régis
PR
El-Benna
Jamel
J
Leynaert
Benedicte
B
Leynaert
A Benedicte
AB
Aubier
Michel
M
Boczkowski
Jorge
J
D000328:Adult; D000818:Animals; D015536:Down-Regulation / Q000187:drug effects; D000074623:Dual Oxidases; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D051547:Heme Oxygenase-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation; D008168:Lung / Q000201:enzymology* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC; D009077:Mucins / Q000378:metabolism; D009093:Mucus / Q000378:metabolism*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012907:Smoking / Q000009:adverse effects*; D013183:Sputum / Q000201:enzymology
C524678:MUC5AC protein, human; C524679:Muc5ac protein, mouse; C524680:Muc5ac protein, rat; D055271:Mucin 5AC; D009077:Mucins; D006427:Hemin; D000074623:Dual Oxidases; D051547:Heme Oxygenase-1; D019255:NADPH Oxidases; C519130:Duox1 protein, mouse; C524752:Duox1 protein, rat
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