The Effect of Selective Cyclooxygenase-2 Inhibitor on the Expression of Hypoxia-Inducible Factor-1alpha in Nasal Polyps / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs in the world. NSAIDs are known to be potent inhibitors of the cyclooxygenase (COX) enzymes, a family of enzymes that catalyze the conversion of arachidonic acid to prostagladins. Expression of the gene encoding COX-2 might be regulated by hypoxia. Hypoxiainducible factors (HIFs) are activated by hypoxia. HIFs function in the hypoxic environment to orchestrate adaptational adjustments of vascular homeostasis through the activation of several dozens of target genes. The purpose of this study was to investigate whether a selective COX-2 inhibitor inhibits HIF-1alpha in human nasal polyps. SUBJECTS AND METHOD: Seven patients with nasal polyps with chronic sinusitis were selected. After the first biopsy, all patients were treated with selective cyclooxygenase inhibitor (Celebrax(R), 100mg, twice daily) for 7 days. At the end of the treatment period, a second set of biopsies was taken. HIF-1alpha messenger RNA (mRNA) production was measured by reverse transcriptase polymerase chain reaction and the protein expression of HIF-1alpha was determined by immunohistochemical staining. RESULTS: The expression of HIF-1alpha mRNA and protein were detected in nasal polyps. There was no significant difference in the mean level of HIF-1alpha mRNA between selective COX-2 inhibitoruntreated and treated nasal polyps (p>0.05). Immunohistochemistry shows diffuse and increased expression of HIF-1alpha in the nuclei of pseudostratified columnar epithelial cells. Endothelial cells and inflammatory cells including lymphocytes and histiocytes were expressed with HIF-1alpha in the stroma. Subcellular localization of HIF-1alpha were found mostly in the nucleus, but were occasionally observed in the cytoplasm of histiocytes. The expression of HIF-1alpha protein was not significantly different between selective COX-2 inhibitor-treated and selective COX-2 inhibitor-untreated nasal polyps (p>0.05). CONCLUSION: Selective COX-2 inhibitor did not inhibit HIF-1alpha expression in nasal polyps. Further studies are needed to find out the effect of selective COX-2 inhibitor on nasal polyps.