title: The role of hepatocyte growth factor/c-Met in chronic rhinosinusitis with nasal polyps.
abstract: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287-0910, USA.
authors.forename: Douglas D
authors.initials: DD
authors.lastname: Reh
authors.forename: Murugappan
authors.initials: M
authors.lastname: Ramanathan
authors.forename: Babar
authors.initials: B
authors.lastname: Sultan
authors.forename: Yadong
authors.initials: Y
authors.lastname: Wang
authors.forename: Lindsey
authors.initials: L
authors.lastname: May
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
mesh_terms: 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
chemical_list: C120429:CCL26 protein, human; D000075906:Chemokine CCL26; D019742:Chemokines, CC; D018793:Interleukin-13; D017228:Hepatocyte Growth Factor
references.citation: Otolaryngol Head Neck Surg. 2004 Dec;131(6 Suppl):S1-62
references.pmid: 15577816
references.citation: Otolaryngol Clin North Am. 2005 Dec;38(6):1193-201, viii
references.pmid: 16326178
references.citation: Laryngoscope. 2007 Oct;117(10):1834-8
references.pmid: 17690616
references.citation: J Biochem. 1996 Apr;119(4):591-600
references.pmid: 8743556
references.citation: Curr Allergy Asthma Rep. 2005 Nov;5(6):472-6
references.pmid: 16216172
references.citation: Laryngoscope. 2004 May;114(5):811-3
references.pmid: 15126735
references.citation: Am J Rhinol. 2003 Nov-Dec;17(6):321-6
references.pmid: 14750606
references.citation: Otolaryngol Head Neck Surg. 2006 Jun;134(6):991-6
references.pmid: 16730544
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2004 Jun;12(3):237-42
references.pmid: 15167036
references.citation: Curr Opin Otolaryngol Head Neck Surg. 2008 Jun;16(3):270-4
references.pmid: 18475084
references.citation: Am J Rhinol. 2007 Jan-Feb;21(1):84-8
references.pmid: 17283567
references.citation: Curr Allergy Asthma Rep. 2003 Nov;3(6):523-31
references.pmid: 14531975
references.citation: Arch Otolaryngol Head Neck Surg. 2006 Sep;132(9):985-9
references.pmid: 16982975
references.citation: Laryngoscope. 2004 Oct;114(10):1827-32
references.pmid: 15454780
references.citation: Int Arch Allergy Immunol. 2008;146 Suppl 1:82-7
references.pmid: 18504413
references.citation: Int Arch Allergy Immunol. 2009;149 Suppl 1:14-20
references.pmid: 19494499
references.citation: Am J Physiol. 1997 Jun;272(6 Pt 1):L1115-20
references.pmid: 9227512
references.citation: Acta Otolaryngol. 2006 Jul;126(7):724-9
references.pmid: 16803712
references.citation: Laryngoscope. 2008 May;118(5):881-9
references.pmid: 18391768
references.citation: Am J Rhinol. 2008 Mar-Apr;22(2):115-21
references.pmid: 18416964