title: Hypoxia stimulates inflammatory and fibrotic responses from nasal-polyp derived fibroblasts.
abstract: OBJECTIVE
  Chronic sinusitis is primarily an inflammatory disorder characterized by hyperplasia of immune cells and sinus tissue. Nasal mucosal swelling or polyps can occlude the sinus ostia, decreasing the level of oxygen available to the sinus tissue. Hypoxia in many diseases results in increased recruitment of inflammatory cells and release of cytokines. The role of hypoxia in chronic sinusitis is unknown. We hypothesized that hypoxia induces production of mediators that recruit cells into the sinus tissue and are involved in remodeling of the nasal mucosa.
  
  
  METHODS
  We compared data from unstimulated nasal-polyp derived fibroblasts with those cultured in hypoxic (10% O2) and anoxic (0% O2) environments. Changes in mRNA expression and protein levels of cytokines and chemokines were measured along with changes in cellular proliferation.
  
  
  RESULTS
  Hypoxic conditions did not change the proliferative capacity of fibroblasts, whereas anoxia led to a 40% reduction in cellular proliferation (P < .05). Hypoxia led to increases in secretion of many cytokines including vascular endothelial growth factor and CCL11. As a marker of remodeling, procollagen and fibronectin production were significantly increased under hypoxic conditions.
  
  
  CONCLUSIONS
  Hypoxic conditions present in the sinus tissue could increase production of proinflammatory and remodeling cytokines that contribute to the inflammation observed in sinusitis. Surgical intervention may help decrease inflammation by allowing reoxygenation of the sinus cavity and decrease the hypoxic induction of cytokines and remodeling factors.
authors.affiliation: Asthma and Allergic Disease Center, Beirne Carter Center for Immunology, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
authors.forename: S Brandon
authors.initials: SB
authors.lastname: Early
authors.forename: Kathleen
authors.initials: K
authors.lastname: Hise
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Han
authors.forename: Larry
authors.initials: L
authors.lastname: Borish
authors.forename: John W
authors.initials: JW
authors.lastname: Steinke
mesh_terms: D049109:Cell Proliferation; D002478:Cells, Cultured; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000473:pathology*; D051793:Hypoxia-Inducible Factor 1 / Q000096:biosynthesis / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D018925:Chemokines; D051793:Hypoxia-Inducible Factor 1; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger