title: Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis.
abstract: BACKGROUND
  Chronic rhinosinusitis (CRS) is a multifactorial disease of unknown cause characterized by sinonasal inflammation, increased mucus production, and defective mucociliary clearance. Expression of Pendrin, an epithelial anion transporter, is increased in asthma and chronic obstructive pulmonary disease. Pendrin increases mucus production and regulates mucociliary clearance.
  
  
  OBJECTIVE
  We sought to investigate the expression of pendrin and the mucus-related protein Muc5AC in sinonasal tissues of control subjects and patients with CRS and to evaluate the regulation of pendrin expression in nasal epithelial cells (NECs) in vitro.
  
  
  METHODS
  The expression and distribution of pendrin in sinonasal tissues was analyzed by using real-time PCR, immunoblot analysis, and immunohistochemistry. Differentiated NECs were used to study the regulation of pendrin expression.
  
  
  RESULTS
  Increased pendrin expression was observed in nasal polyp (NP) tissue of patients with CRS. Immunohistochemistry analysis revealed that pendrin was largely restricted to the epithelial layer. Pendrin expression significantly correlated with inflammatory cell markers, suggesting that the factors made by these cells might induce pendrin expression. Furthermore, both pendrin and periostin levels (a biomarker in asthma) correlated with IL-13 levels, suggesting that pendrin can be induced by this cytokine in sinonasal tissues. Expression of the mucus component protein Muc5AC correlated weakly with pendrin expression, indicating that pendrin might modulate mucus production in NPs. In cultured NECs pendrin expression was induced by TH2 cytokines and induced synergistically when TH2 cytokines were combined with IL-17A. Interestingly, human rhinovirus had a potentiating effect on IL-13-induced pendrin expression. Dexamethasone suppressed pendrin expression, suggesting that the therapeutic benefit of dexamethasone in asthmatic patients and those with CRS might involve regulation of pendrin expression.
  
  
  CONCLUSIONS
  TH2-mediated pendrin expression is increased in NPs of patients with CRS and might lead to increased inflammation, mucus production, and decreased mucociliary clearance.
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Sudarshan
authors.initials: S
authors.lastname: Seshadri
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Department of Otolaryngology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Purkey
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Homma
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Andrew Wonho
authors.initials: AW
authors.lastname: Choi
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Roderick
authors.initials: R
authors.lastname: Carter
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Lydia
authors.initials: L
authors.lastname: Suh
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: James
authors.initials: J
authors.lastname: Norton
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Kathleen E
authors.initials: KE
authors.lastname: Harris
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: David B
authors.initials: DB
authors.lastname: Conley
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.affiliation: Department of Biochemistry and Molecular Biology, The Centre of Postgraduate Medical Education, Marymoncka 99/103, Warsaw 01-813, Poland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Czarnocka
authors.affiliation: Division of Endocrinology, Metabolism, and Molecular Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Kopp
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Anju T
authors.initials: AT
authors.lastname: Peters
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Leslie C
authors.initials: LC
authors.lastname: Grammer
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Chandra
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Tan
authors.affiliation: Department of Otolaryngology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Kern
authors.affiliation: Division of Allergy and Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.|Department of Otolaryngology-Head and Neck Surgery, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Schleimer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002908:Chronic Disease; D016207:Cytokines / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D055271:Mucin 5AC / Q000235:genetics; D009297:Nasal Mucosa / Q000166:cytology / Q000378:metabolism; D009298:Nasal Polyps / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D012220:Rhinitis / Q000378:metabolism*; D012852:Sinusitis / Q000378:metabolism*; D000076988:Sulfate Transporters; D055815:Young Adult
chemical_list: D016207:Cytokines; C524678:MUC5AC protein, human; D026901:Membrane Transport Proteins; D055271:Mucin 5AC; D012333:RNA, Messenger; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters
keywords: Muc5AC; Pendrin; SLC26A4; chronic rhinosinusitis; mucociliary clearance; mucus; nasal epithelial cells; nasal polyp; periostin