Regulation of cyclooxygenase-1 and -2 expression in human nasal mucosa. Effects of cytokines and dexamethasone.
BACKGROUND
Cyclooxygenase (COX) converts arachidonic acid in prostanoids. COX exists in two isoforms, COX-1 is the constitutive whereas COX-2 is the inducible isoform. The regulation of COX-1 and COX-2 expression in nasal mucosa has not been previously reported.


OBJECTIVE
We studied expression and regulation by cytokines and corticosteroids of COX-1 and COX-2 in human nasal mucosa. Cultured human nasal explants from patients undergoing corrective nasal mucosal resection were examined for COX-1 and COX-2 expression by semiquantitative competitive PCR and Western blot.


METHODS
Explants were incubated with pro-(IFNgamma, IL-1beta, and TNF-alpha) and anti(IL-10) inflammatory cytokines and dexamethasone. The mechanisms which regulate COX-2 mRNA expression were studied using inhibitors of translation (Actinomycin D) and transcription (Cicloheximide).


RESULTS
The baseline expression of COX-2 mRNA was higher than COX-1 mRNA. Once in culture, there was a slight spontaneous up-regulation of COX-1 and a strong COX-2 mRNA and protein up-regulation. The incubation of nasal explants with pro-inflammatory cytokines increased the expression of COX-2 mRNA and protein, from 1 to 24 h of incubation in a dose-related manner. The regulation of these effects occurred at both transcriptional and post-transcriptional levels. Dexamethasone and IL-10 abrogated cytokine-induced COX-2 mRNA and protein expression. Pro-inflammatory cytokines, dexamethasone and IL-10 had no effect on COX-1 mRNA expression.


CONCLUSIONS
As prostanoids have important regulatory effects on the immunologically mediated inflammatory responses, our findings throw some light on the mechanisms that regulate the enzymes which produce these metabolites in the human airway.
Fernández-Morata
J C
JC
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Servei d'ORL, Departament de Medicina, Universitat de Barcelona, Spain.
Mullol
J
J
Fuentes
M
M
Pujols
L
L
Roca-Ferrer
J
J
Pérez
M
M
Xaubet
A
A
Picado
C
C
D000328:Adult; D015153:Blotting, Western; D046508:Culture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000494:pharmacology*; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D016753:Interleukin-10 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D009297:Nasal Mucosa / Q000201:enzymology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D005938:Glucocorticoids; D007527:Isoenzymes; D008565:Membrane Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D012333:RNA, Messenger; D016753:Interleukin-10; D003609:Dactinomycin; D003907:Dexamethasone; D003513:Cycloheximide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases