Sex-Specific Differences In Disease Severity In Patients With Chronic Rhinosinusitis With Nasal Polyps

Abstract

S U N D A Y 583 Regulation Of Expression Of Pendrin Protein In CRS With Nasal Polyps and In Airway Epithelial Cells Dr. Sudarshan Seshadri, PhD, Dr. Xiang Lu, MD, PhD, Mr. Matthew Purkey, BS, Dr. Tetsuya Homma, MD, Mr. Andrew Choi, Mr. Roderick Carter, BSc, Mr. James Norton, MS, Ms. Lydia Suh, BSc, Dr. Atsushi Kato, PhD, Prof. Pedro C. Avila, MD, FAAAAI, Dr. Anju T. Peters, MD, FAAAAI, Dr. David Conley, MD, Dr. Rakesh Chandra, MD, Dr. Bruce K. Tan, MD, Dr. Leslie C. Grammer, MD, FAAAAI, Dr. Robert C. Kern, MD, Dr. Robert P. Schleimer, PhD, FAAAAI; Department of Medicine, Division of Allergy-Immunology, Northwestern University Feinberg School of Medicine, Chicago, IL, Department of Otolaryngology, Northwestern University Feinberg School of Medicine, Chicago, IL, Northwestern University, Chicago, IL, Division of Allergy-Immunology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. RATIONALE: Pendrin is an anion transporter expressed by airway epithelial cells. Pendrin functions as a regulator of inflammation, mucus production and in the maintenance of air-surface liquid (ASL). We and others reported that expression of pendrin mRNA was elevated in nasal polyps (NP) of patients with chronic rhinosinusitis (CRS). In this study we analyzed the regulation of pendrin protein expression in NPs of patients with CRS and also in nasal epithelial cells (NECs). METHODS: Tissue samples were collected and analyzed by real-time PCR and/or immunoblot analysis for expression of pendrin and various cytokines. NECs were stimulated with various cytokines, dsRNA and rhinovirus to analyze the regulation of pendrin expression. RESULTS: Immunoblot analysis indicated that pendrin protein was increased in NP of patients with CRS compared to control uncinates (3.5 fold, p<0.01, n59-16), although the molecular size of pendrin was less than the expected 80-100 kDa of the fully glycosylated form. In cultured NECs, glycosylated pendrin expression was increased by treatment with IL-13 and IL-17, and profoundly so when these two cytokines were combined. IL-13 and IL-17 also potentiated pendrin expression induced by dsRNA or rhinovirus. Pendrin mRNA expression in vivo correlated with IL-13 and IL-17 mRNA in sinonasal tissues. CONCLUSIONS: Our findings confirm in vivo expression of pendrin protein in NP of patients with CRS and also indicate that pendrin expression is induced synergistically by Th2/Th17 cytokines in vitro. Profound induction of pendrin by rhinovirus and Th2/Th17 cytokines suggests that pendrin may be involved in viral induced exacerbations in CRS and/or asthma