The role of hepatocyte growth factor/c-Met in chronic rhinosinusitis with nasal polyps.
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.


CONCLUSIONS
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.
Reh
Douglas D
DD
Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-0910, USA.
Ramanathan
Murugappan
M
Sultan
Babar
B
Wang
Yadong
Y
May
Lindsey
L
Lane
Andrew P
AP
D002469:Cell Separation; D002478:Cells, Cultured; D000075906:Chemokine CCL26; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics; D002908:Chronic Disease; D018450:Disease Progression; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005434:Flow Cytometry; D017228:Hepatocyte Growth Factor / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D009298:Nasal Polyps; D010256:Paranasal Sinuses / Q000473:pathology*; D012220:Rhinitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D012852:Sinusitis / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D058408:Th1-Th2 Balance
C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D018793:Interleukin-13; D017228:Hepatocyte Growth Factor
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