Nuclear factor-kappaB activity is down-regulated in nasal polyps from aspirin-sensitive asthmatics.
BACKGROUND
We examined whether a decreased activity of nuclear factor(NF)-kappaB), a transcriptional regulator of cyclooxygenase-2 (COX-2), could account for down-regulation of COX-2 in nasal polyps of aspirin-sensitive asthmatics.


METHODS
Nasal polyps were obtained from 17 aspirin-intolerant asthma/rhinitis patients (AIAR; 7 men, mean age 48 +/- 12 years) and 23 aspirin-tolerant asthma/rhinitis patients (ATAR; 12 men, mean age 65 +/- 11 years). COX-2 mRNA expression was measured using semiquantitative reverse transcriptase competitive polymerase chain reaction (RT-PCR), and the results were expressed as mean +/- standard error of 106 molecules of mRNA/ micro g of total RNA. NF-kappaB binding was measured with 32P-labeled oligonucleotides and electrophoretic mobility shift assay (EMSA), and the results were expressed as a percentage with respect to the mean EMSA obtained in 19 healthy nasal mucosa.


RESULTS
The mean levels of COX-2 mRNA expression (0.25 +/- 0.06) and NF-kappaB activity (89 +/- 13) in nasal polyps from AIAR were significantly lower than in polyps from ATAR (COX-2 = 1.58 +/- 0.50, and NF-kappaB = 143 +/- 12, P < 0.01 and P < 0.05, respectively). Levels of COX-2 mRNA and NF-kappaB activity in polyps from patients on corticosteroid therapy did not differ statistically from those who were not on this therapy before polypectomy.


CONCLUSIONS
This study shows that the low expression of COX-2 mRNA in nasal polyps from aspirin-sensitive patients is associated with a down-regulation of NF-kappaB activity.
Picado
C
C
Servei de Pneumologia i Allèrgia Respiratòria, Institut Clínic de Pneumologia i Cirurgia Toràcica, Universitat de Barcelona, Barcelona, Spain.
Bioque
G
G
Roca-Ferrer
J
J
Pujols
L
L
Mullol
J
J
Benitez
P
P
Bulbena
O
O
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D001241:Aspirin / Q000009:adverse effects*; D001249:Asthma / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism*; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000009:adverse effects*; D015536:Down-Regulation / Q000187:drug effects*; D004342:Drug Hypersensitivity / Q000209:etiology* / Q000378:metabolism*; D004586:Electrophoresis; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009297:Nasal Mucosa / Q000378:metabolism / Q000473:pathology; D009298:Nasal Polyps / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D012221:Rhinitis, Allergic, Perennial / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D013223:Statistics as Topic; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016896:Treatment Outcome
D000305:Adrenal Cortex Hormones; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin