Introduction. Antimicrobial peptides and proteins (AMPs) constitute the first line of defense against pathogenic microorganisms in the airway. The association between AMPs and chronic rhinosinusitis with nasal polyps (CRSwNP) requires further investigations. This study is aimed at investigating the expression and regulation of major dysregulated AMPs in the nasal mucosa of CRSwNP. Methods. The expression of AMPs was analyzed in nasal tissue from patients with eosinophilic (E) CRSwNP and nonECRSwNP and healthy subjects using RNA sequencing. The 10 most abundant AMPs expressed differentially in CRSwNP patients were verified by real-time PCR, and of these, the expression and regulation of secretory leukoprotease inhibitor (SLPI) and clusterin (CLU) were investigated further. Results. The 10 most abundant AMPs expressed differentially in CRSwNP compared to healthy control, regardless of subtypes, included BPIFA1, BPIFB1, BPIFB2, CLU, LTF, LYZ, and SLPI, which were downregulated, and S100A8, S100A9, and HIST1H2BC, which were upregulated. ELISA and immunofluorescence confirmed the decreased expression of SLPI and CLU levels in CRSwNP. SLPI is expressed in both nasal epithelial cells and glandular cells, whereas CLU is mainly expressed in glandular cells. AB/PAS staining further demonstrated that both SLPI and CLU were mainly produced by mucous cells in submucosal glands. Furthermore, the numbers of submucosal glands were significantly decreased in nasal polyp tissue of CRSwNP compared to nasal tissue of controls. SLPI was downregulated by TGF-beta 1 and IL-4 in cultured nasal tissues in vitro, while CLU expression was inhibited by TGF-beta 1. Glucocorticoid treatment for 2 weeks significantly increased the expression of all downregulated AMPs, but not LYZ. Additionally, budesonide significantly increased the expression of SLPI and CLU in cultured nasal tissues. Conclusion. The expression of major antimicrobial proteins is significantly decreased in nasal tissue of CRSwNP. The expression of SLPI and CLU is correlated with the numbers of submucosal glands and regulated by inflammatory cytokines and glucocorticoids.
基金：
National Key R&D Program of China [2016YFC0905200]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81800882, 82025010, 81870698, 81630023]; Program for the Changjiang Scholars and Innovative Research TeamProgram for Changjiang Scholars & Innovative Research Team in University (PCSIRT) [IRT13082]; Beijing Municipal Administration of Hospitals' Mission Plan [SML20150203]; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [XMLX201816]; Capital Health Development Foundation [2016-1-2052]
第一作者机构：[1]Capital Med Univ, Beijing Tongren Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China[2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing 100005, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Capital Med Univ, Beijing Tongren Hosp, Dept Otolaryngol Head & Neck Surg, Beijing 100730, Peoples R China[2]Beijing Inst Otolaryngol, Beijing Key Lab Nasal Dis, Beijing 100005, Peoples R China[3]Capital Med Univ, Beijing Tongren Hosp, Dept Allergy, Beijing 100730, Peoples R China
推荐引用方式(GB/T 7714)：
Huang Yanran,Wang Ming,Hong Yu,et al.Reduced Expression of Antimicrobial Protein Secretory Leukoprotease Inhibitor and Clusterin in Chronic Rhinosinusitis with Nasal Polyps[J].JOURNAL OF IMMUNOLOGY RESEARCH.2021,2021:doi:10.1155/2021/1057186.
APA：
Huang, Yanran,Wang, Ming,Hong, Yu,Bu, Xiangting,Luan, Ge...&Zhang, Luo.(2021).Reduced Expression of Antimicrobial Protein Secretory Leukoprotease Inhibitor and Clusterin in Chronic Rhinosinusitis with Nasal Polyps.JOURNAL OF IMMUNOLOGY RESEARCH,2021,
MLA：
Huang, Yanran,et al."Reduced Expression of Antimicrobial Protein Secretory Leukoprotease Inhibitor and Clusterin in Chronic Rhinosinusitis with Nasal Polyps".JOURNAL OF IMMUNOLOGY RESEARCH 2021.(2021)
