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The effect of hypoxia and cycloxygenase inhibitors on nasal polyp derived fibroblasts.
MedLine Citation:
PMID:  21315485     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND AND PURPOSE: The pathogenesis of chronic rhinosinusitis with nasal polyposis is unknown. Chronic inflammation along with local tissue hypoxia may effect polyp's growth. Activation of Cycloxygenases may also be involved. COX-2 up-regulates in response to different stimuli including hypoxia. Its activation is associated with enhanced cell proliferation. Histologically, besides inflammatory cells, increased stromal fibrosis is seen in nasal polyposis. The aims of this study were to test whether hypoxia amplifies nasal polyp fibroblasts proliferation, whether treatment with various COX inhibitors could influence fibroblasts, and whether this effect may be modulated in response to different oxygenation conditions. MATERIALS AND METHODS: Polyp fibroblasts were incubated under hypoxic or normoxic conditions with or without NSAIDs at different concentrations for 12 or 24 hours. Cell proliferation was quantified using BrdU ELISA. Metabolic activity was evaluated using MTT assay. Cell death was measured using Annexin V staining and FACS scan. RESULTS: No significant difference was found between proliferation of fibroblasts treated under hypoxia or normoxia. Cells incubated with indomethacin proliferated in a slightly enhanced manner compared with non-treated cells. Celecoxib inhibited fibroblast proliferation (P < .001) but did not influence cell survival. Metabolic activity of cells treated with celecoxib was significantly reduced (P < .003), unlike cells treated with indomethacin or rofecoxib. CONCLUSION: Hypoxia does not affect fibroblasts proliferation. It may contribute to nasal polyposis pathogenesis in other ways. The anti-proliferative effect of celecoxib may be associated with cell cycle arrest rather than with pro-apoptotic activity. Celecoxib may be considered for treating nasal polyposis.
Authors:
Smadar Cohen; Alon Nissim Ben Efraim; Francesca Levi-Schaffer; Ron Eliashar
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-2-9
Journal Detail:
Title:  American journal of otolaryngology     Volume:  -     ISSN:  1532-818X     ISO Abbreviation:  -     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-2-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000029     Medline TA:  Am J Otolaryngol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Hebrew University School of Medicine - Hadassah Medical Center, Jerusalem, Israel.
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