Increased expression of the epithelial anion transporter pendrin/SLC26A4 in nasal polyps of patients with chronic rhinosinusitis - 04/12/15
, Xiang Lu, MD, PhD a, b, ∗, Matthew R. Purkey, BS a, Tetsuya Homma, MD, PhD a, Andrew Wonho Choi, BS a, Roderick Carter, BS a, Lydia Suh, BSc a, James Norton, MS a, Kathleen E. Harris, MS a, David B. Conley, MD c, Atsushi Kato, PhD a, Pedro C. Avila, MD a, Barbara Czarnocka, PhD d, Peter A. Kopp, MD e, Anju T. Peters, MD a, Leslie C. Grammer, MD a, Rakesh K. Chandra, MD c, Bruce K. Tan, MD c, Zheng Liu, MD b, Robert C. Kern, MD c, Robert P. Schleimer, PhD a, c, ⁎ 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.
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 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.
Le texte complet de cet article est disponible en PDF.Key words : Pendrin, SLC26A4, periostin, Muc5AC, chronic rhinosinusitis, nasal polyp, mucus, mucociliary clearance, nasal epithelial cells
Abbreviations used : ALI, CRS, CRSsNP, CRSwNP, NEC, NP, Poly(I:C), UT
Plan
| Supported in part by National Institutes of Health grants R37HL068546, R01HL078860, and U19AI106683 and by the Ernest S. Bazley Foundation (to R.P.S.). X.L. was supported by National Natural Science Foundation of China (NSFC) grant 81020108018 (to Z.L.). |
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| Disclosure of potential conflict of interest: K. E. Harris is employed by Northwestern University. A. Kato has received research support from the National Institutes of Health (NIH; R01 AI104733 and R21 HL113913) and the Janssen Research Fund. P. C. Avila has received research support from the NIH, Roche/Genentech, AstraZeneca, the National Institute of Allergy and Infectious Diseases (NIAID)/Immune Tolerance Network (ITN), Novartis, and Circassia. A. T. Peters is an advisory board member for Baxter and for Meda. L. C. Grammer has received research support from the NIH, the Bazley Foundation (grant), the Food Allergy Network, and S&C Electric; has received travel support from the NIH; has received consultancy fees from Astellas Pharmaceuticals; is employed by Northwestern University and the Northwestern Medical Faculty Foundation; has received lecture fees from the American Academy of Allergy, Asthma & Immunology and Mount Sinai, New York, NY; and has received royalties from Lippincott, UpToDate, BMJ, and Elsevier. B. K. Tan has received research support from the NIH (K23 DC012067, U19 AI106683). Z. Liu has received support from the National Natural Science Foundation of China (grant 81020108018). R. P. Schleimer has received research support from the NIH; has received consultancy fees from Intersect ENT, GlaxoSmithKline, Allakos, Aurasense, Merck, BioMarck, and Sanofi; and has stock/stock options in Allakos, Aurasense, and BioMarck. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 136 - N° 6
P. 1548 - décembre 2015 Retour au numéro
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