The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps

• Published in: Journal of allergy and clinical immunology Vol. 133; no. 2; pp. 420 - 428.e12
• Main Authors: Wei, Yi, MD, Xia, Wentong, MD, Ye, Xingling, MD, Fan, Yunping, PhD, Shi, Jianbo, PhD, Wen, Weiping, PhD, Yang, Pingchang, PhD, Li, Huabin, MD
• Format: Journal Article
• Language: English
• Published: New York, NY Mosby, Inc 01.02.2014; Elsevier; Elsevier Limited
• Subjects: Adult; Allergy and Immunology; Antimicrobial agents; Biological and medical sciences; Cell culture; Cell Line, Tumor; Cells, Cultured; chronic rhinosinusitis; Cloning; cytokine; Cytokines - immunology; Disease; eosinophil; Eosinophilia - immunology; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; glucocorticoid; Glucocorticoids - pharmacology; Glycoproteins - genetics; Glycoproteins - immunology; Humans; Immunopathology; Male; Medical sciences; Methods; Middle Aged; nasal polyps; Nasal Polyps - immunology; Non tumoral diseases; Otorhinolaryngology. Stomatology; Phosphoproteins - genetics; Phosphoproteins - immunology; Proteins; Rhinitis - immunology; RNA, Messenger - metabolism; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; Short palate, lung, and nasal epithelium clone 1; Sinusitis - immunology; Studies; submucosal gland; Surgery; Toll-like receptor; Upper respiratory tract, upper alimentary tract, paranasal sinuses, salivary glands: diseases, semeiology; Young Adult; Short palate, lung, and nasal epithelium clone 1; PAS; LPLUNC2; Major basic protein; CRS; PLUNC; SPLUNC1; CRSwNP; Polyp epithelial cell; CRSsNP; Long palate, lung, and nasal epithelium clone 2; Periodic acid–Schiff; nasal polyps; MBP; TLR; eosinophil; Toll-like receptor; submucosal gland; hpf; cytokine; Bactericidal/permeability-increasing protein; Quantitative real-time PCR; glucocorticoid; Hematoxylin and eosin; H&E; High-power field; qRT-PCR; Palate, lung, and nasal epithelium clone; PEC; Chronic rhinosinusitis without nasal polyps; Chronic rhinosinusitis with nasal polyps; chronic rhinosinusitis; Glyceraldehyde-3-phosphate dehydrogenase; BPI; GAPDH; Clonality; Nose disease; Nasal polyp; Rhinitis; Upper respiratory tract; Lung; Granulocyte; Toll like receptor; Respiratory system; Glucocorticoid; Antimicrobial agent; Sinusitis; Short palate; Immunology; Nose; ENT disease; Submucosa; Clone; Immunopathology; Cytokine; Epithelium; Eosinophil; Protein; Chronic; Paranasal sinus disease; Palate; and nasal epithelium clone 1; Chronic rhinosinusitis
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.09.052

Background Chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with aberrant host defense responses. However, whether innate immunity is similarly impaired in patients with eosinophilic and those with noneosinophilic CRSwNP remains unclear. Objectives We sought to evaluate the expression and possible modulation of short palate, lung, and nasal epithelium clone 1 (SPLUNC1), an innate immune molecule, in the 2 CRSwNP subsets. Methods Polyp tissue and uncinate processes were collected from 40 patients with CRSwNP, 27 patients with chronic rhinosinusitis without nasal polyps (CRSsNP), and 22 control subjects. Expression of SPLUNC1; Toll-like receptor (TLR) 2, TLR3, and TLR4; and the proinflammatory cytokines IL-1α, IL-4, IL-13, IL-17A, and IFN-γ was examined in nasal tissues. Additionally, SPLUNC1 expression in response to specific inflammatory stimulation was measured in cultured polyp epithelial cells and A549 cells. Results Polyp tissues exhibited significantly decreased expression of SPLUNC1 and other innate immune molecules compared with uncinate process tissues from patients with CRSwNP ( P  < .05), patients with CRSsNP, and healthy control subjects. Moreover, the eosinophilic CRSwNP subset exhibited significantly decreased SPLUNC1 expression and numbers of submucosal glands, as well as significantly increased IL-4 and IL-13 mRNA levels, compared with the noneosinophilic subset ( P  < .05). Accordingly, SPLUNC1 expression in polyp epithelial cells was significantly inhibited by IL-4 and IL-13 stimulation in vitro but was significantly upregulated after stimulation with TLR agonists and glucocorticoids ( P  < .05). Conclusion Differential SPLUNC1 suppression between the eosinophilic and noneosinophilic CRSwNP subsets suggests that they possess distinct pathogenic mechanisms. This finding might benefit the design of appropriate therapeutic interventions targeted to each subset.