title: The antimicrobial protein short palate, lung, and nasal epithelium clone 1 (SPLUNC1) is differentially modulated in eosinophilic and noneosinophilic chronic rhinosinusitis with nasal polyps.
abstract: 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.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University, and the Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University, and the Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
authors.forename: Wentong
authors.initials: W
authors.lastname: Xia
authors.affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University, and the Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
authors.forename: Xingling
authors.initials: X
authors.lastname: Ye
authors.affiliation: Department of Otolaryngology, Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Fan
authors.affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University, and the Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Shi
authors.affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University, and the Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China.
authors.forename: Weiping
authors.initials: W
authors.lastname: Wen
authors.affiliation: Health Science Center, Shenzhen University, Shenzhen, China.
authors.forename: Pingchang
authors.initials: P
authors.lastname: Yang
authors.affiliation: Allergy and Cancer Center, Otorhinolaryngology Hospital, First Affiliated Hospital of Sun Yat-sen University, and the Otorhinolaryngology Institute of Sun Yat-sen University, Guangzhou, China; Department of Otolaryngology, Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: allergyli@163.com.
authors.forename: Huabin
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004802:Eosinophilia / Q000276:immunology*; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009298:Nasal Polyps / Q000276:immunology*; D010750:Phosphoproteins / Q000235:genetics / Q000276:immunology*; D012333:RNA, Messenger / Q000378:metabolism; D012220:Rhinitis / Q000276:immunology*; D012852:Sinusitis / Q000276:immunology*; D055815:Young Adult
chemical_list: C485599:BPIFA1 protein, human; D016207:Cytokines; D005938:Glucocorticoids; D006023:Glycoproteins; D010750:Phosphoproteins; D012333:RNA, Messenger
keywords: BPI; Bactericidal/permeability-increasing protein; CRS; CRSsNP; CRSwNP; Chronic rhinosinusitis; Chronic rhinosinusitis with nasal polyps; Chronic rhinosinusitis without nasal polyps; GAPDH; Glyceraldehyde-3-phosphate dehydrogenase; H&E; Hematoxylin and eosin; High-power field; LPLUNC2; Long palate, lung, and nasal epithelium clone 2; MBP; Major basic protein; PAS; PEC; PLUNC; Palate, lung, and nasal epithelium clone; Periodic acid–Schiff; Polyp epithelial cell; Quantitative real-time PCR; SPLUNC1; Short palate, lung, and nasal epithelium clone 1; TLR; Toll-like receptor; chronic rhinosinusitis; cytokine; eosinophil; glucocorticoid; hpf; nasal polyps; qRT-PCR; submucosal gland