title: The effect of hypoxia and cycloxygenase inhibitors on nasal polyp derived fibroblasts.
abstract: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.affiliation: Hebrew University School of Medicine - Hadassah Medical Center, Jerusalem, Israel.
authors.forename: Smadar
authors.initials: S
authors.lastname: Cohen
authors.forename: Alon Nissim Ben
authors.initials: AN
authors.lastname: Efraim
authors.forename: Francesca
authors.initials: F
authors.lastname: Levi-Schaffer
authors.forename: Ron
authors.initials: R
authors.lastname: Eliashar
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000068579:Celecoxib; D015687:Cell Hypoxia; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009298:Nasal Polyps / Q000188:drug therapy / Q000473:pathology; D011720:Pyrazoles / Q000494:pharmacology; D012016:Reference Values; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D000068579:Celecoxib; D007213:Indomethacin