Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:136

Article

Seshadri, Sudarshan¹  Lu, Xiang^1,4  Purkey, Matthew R.¹  Homma, Tetsuya¹  Choi, Andrew Wonho¹  Carter, Roderick¹  Suh, Lydia¹  Norton, James¹  Harris, Kathleen E.¹  Conley, David B.²  Kato, Atsushi¹  Avila, Pedro C.¹  Czarnocka, Barbara⁵  Kopp, Peter A.³  Peters, Anju T.¹  Grammer, Leslie C.¹  Chandra, Rakesh K.²  Tan, Bruce K.²  Liu, Zheng⁴  Kern, Robert C.²  Schleimer, Robert P.^1,2 

[1] Northwestern Univ, Div Allergy & Immunol, Feinberg Sch Med, Chicago, IL 60611 USA

[2] Northwestern Univ, Dept Otolaryngol Head & Neck Surg, Feinberg Sch Med, Chicago, IL 60611 USA

[3] Northwestern Univ, Div Endocrinol Metab & Mol Med, Feinberg Sch Med, Chicago, IL 60611 USA

[4] Huazhong Univ Sci & Technol, Tongji Med Coll, Tongji Hosp, Dept Otolaryngol, Wuhan 430074, Peoples R China

[5] Ctr Postgrad Med Educ, Dept Biochem & Mol Biol, Warsaw, Poland

关键词: Pendrin;    SLC26A4;    periostin;    Muc5AC;    chronic rhinosinusitis;    nasal polyp;    mucus;    mucociliary clearance;    nasal epithelial cells;   

DOI  :  10.1016/j.jaci.2015.05.024

来源: Elsevier

【 摘 要 】

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. Objectives: 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 T(H)2 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.

【 授权许可】

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