Document Detail


The role of hepatocyte growth factor/c-Met in chronic rhinosinusitis with nasal polyps.
MedLine Citation:
PMID:  20819464     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Hepatocyte growth factor (HGF) is a growth factor thought to attenuate Th2-driven eosinophilic airway inflammatory responses. Increased expression of HGF and its receptor c-Met in nasal polyps suggests a role in disease pathogenesis. The effect of HGF on human sinonasal epithelial cell (SNEC) responses to Th2 inflammatory cytokines in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been explored.
METHODS: SNECs isolated from patients with CRSwNP and control subjects were grown in cell culture at the air-liquid interface. The Th2 cytokine IL-13 was applied for 24 hours in the presence or absence of HGF. Eotaxin-3 and c-Met expression was assessed using real-time PCR, immunohistochemistry, and flow cytometry.
RESULTS: SNECs obtained from both CRSwNP and control subjects showed markedly increased expression of eotaxin-3 after exposure to IL-13. HGF significantly blocked IL-13-induced expression of eotaxin-3 in control SNECs, but not in SNECs derived from CRSwNP subjects.
CONCLUSION: SNECs are active participants in sinonasal mucosal immunity, expressing inflammatory mediators in response to potential pathogens and endogenous cytokines. Although Th2 cytokines can elicit expression of proeosinophilic mediators by SNECs, HGF appears to have a down-regulating effect on this response. In patients with CRSwNP, SNECs are resistant to this attenuation, showing continued IL-13-induced eotaxin-3 expression despite HGF treatment. Abnormalities in the regulation of epithelial cell responses to endogenous cytokines and growth factors may contribute to the persistent eosinophilic inflammatory state in CRSwNP.
Authors:
Douglas D Reh; Murugappan Ramanathan; Babar Sultan; Yadong Wang; Lindsey May; Andrew P Lane
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  American journal of rhinology & allergy     Volume:  24     ISSN:  1945-8932     ISO Abbreviation:  Am J Rhinol Allergy     Publication Date:    2010 Jul-Aug
Date Detail:
Created Date:  2010-09-07     Completed Date:  2011-03-15     Revised Date:  2011-11-10    
Medline Journal Info:
Nlm Unique ID:  101490775     Medline TA:  Am J Rhinol Allergy     Country:  United States    
Other Details:
Languages:  eng     Pagination:  266-70     Citation Subset:  IM    
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-0910, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Separation
Cells, Cultured
Chemokines, CC / biosynthesis,  genetics
Chronic Disease
Disease Progression
Epithelial Cells / immunology,  metabolism*,  pathology
Flow Cytometry
Hepatocyte Growth Factor / immunology,  metabolism*
Humans
Interleukin-13 / immunology,  metabolism
Nasal Polyps
Paranasal Sinuses / pathology*
Rhinitis / immunology*,  pathology,  physiopathology
Sinusitis / immunology*,  pathology,  physiopathology
Th1-Th2 Balance
Grant Support
ID/Acronym/Agency:
R01 AI072502-01A1/AI/NIAID NIH HHS; R01 AI072502-02/AI/NIAID NIH HHS; R01 AI072502-04/AI/NIAID NIH HHS; R01 AI072502-05/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/CCL26 protein, human; 0/Chemokines, CC; 0/Interleukin-13; 67256-21-7/Hepatocyte Growth Factor

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