Regulation of cyclooxygenase-1 and-2 expression in human nasal mucosa. Effects of cytokines and dexamethasone

Background Cyclooxygenase (COX) converts arachidonic acid in prostanoids. C OX exists in two isoforms, COX-1 is the constitutive whereas COX-2 is the i nducible isoform. The regulation of COX-1 and COX-2 expression in nasal muc osa has not been previously reported. Aim We studied expression and regulation by cytokines and corticosteroids o f COX-1 and COX-2 in human nasal mucosa. Cultured human nasal explants from patients undergoing corrective nasal mucosal resection were examined for C OX-1 and COX-2 expression by semiquantitative competitive PCR and Western b lot. Methods Explants were incubated with pro-(IFN gamma, IL-1 beta, and TNF-alp ha) and anti(IL-10) inflammatory cytokines and dexamethasone. The mechanism s which regulate COX-2 mRNA expression were studied using inhibitors of tra nslation (Actinomycin D) and transcription (Cicloheximide). Results The baseline expression of COX-2 mRNA was higher than COX-1 mRNA. O nce 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 expla nts 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 reg ulation of these effects occurred at both transcriptional and post-transcri ptional levels. Dexamethasone and IL-10 abrogated cytokine-induced COX-2 mR NA 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 immunol ogically mediated inflammatory responses, our findings throw some light on the mechanisms that regulate the enzymes which produce these metabolites in the human airway.