Document Detail


Hypoxia stimulates inflammatory and fibrotic responses from nasal-polyp derived fibroblasts.
MedLine Citation:
PMID:  17334314     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES/HYPOTHESIS: 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:
S Brandon Early; Kathleen Hise; Joseph K Han; Larry Borish; John W Steinke
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  The Laryngoscope     Volume:  117     ISSN:  0023-852X     ISO Abbreviation:  Laryngoscope     Publication Date:  2007 Mar 
Date Detail:
Created Date:  2007-03-05     Completed Date:  2007-04-03     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  8607378     Medline TA:  Laryngoscope     Country:  United States    
Other Details:
Languages:  eng     Pagination:  511-5     Citation Subset:  IM    
Affiliation:
Asthma and Allergic Disease Center, Beirne Carter Center for Immunology, Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
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MeSH Terms
Descriptor/Qualifier:
Anoxia / metabolism,  pathology*
Cell Proliferation
Cells, Cultured
Chemokines / genetics,  secretion
Disease Progression
Fibroblasts / metabolism,  pathology*
Gene Expression
Humans
Hypoxia-Inducible Factor 1 / biosynthesis,  genetics
Intercellular Signaling Peptides and Proteins / genetics,  secretion
Nasal Polyps / metabolism,  pathology*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
AI/HL47737/AI/NIAID NIH HHS; AI01793/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Chemokines; 0/Hypoxia-Inducible Factor 1; 0/Intercellular Signaling Peptides and Proteins; 0/RNA, Messenger

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