Huang Yanran, Wang Ming, Hong Yu, Bu Xiangting, Luan Ge, Wang Yang, Li Ying, Lou Hongfei, Wang Chengshuo, Zhang Luo
Department of Otolaryngology, Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China.
Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.
J Immunol Res. 2021 Jan 7;2021:1057186. doi: 10.1155/2021/1057186. eCollection 2021.
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-1 and IL-4 in cultured nasal tissues , while CLU expression was inhibited by TGF-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.
引言：抗菌肽和蛋白质（AMPs）是气道抵御病原微生物的第一道防线。AMPs与伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）之间的关联尚需进一步研究。本研究旨在调查CRSwNP鼻黏膜中主要失调的AMPs的表达及调控情况。 方法：采用RNA测序分析嗜酸性粒细胞性（E）CRSwNP患者、非嗜酸性粒细胞性CRSwNP患者及健康受试者鼻组织中AMPs的表达。通过实时PCR验证在CRSwNP患者中差异表达最丰富的10种AMPs，其中进一步研究了分泌型白细胞蛋白酶抑制剂（SLPI）和簇集素（CLU）的表达及调控情况。 结果：与健康对照相比，无论亚型如何，在CRSwNP中差异表达最丰富的10种AMPs包括下调的BPIFA1、BPIFB1、BPIFB2、CLU、乳铁传递蛋白（LTF）、溶菌酶（LYZ）和SLPI，以及上调的S100A8、S100A9和组蛋白H2BC。酶联免疫吸附测定（ELISA）和免疫荧光证实CRSwNP中SLPI和CLU水平降低。SLPI在鼻上皮细胞和腺细胞中均有表达，而CLU主要在腺细胞中表达。AB/PAS染色进一步表明，SLPI和CLU均主要由黏膜下腺的黏液细胞产生。此外，与对照鼻组织相比，CRSwNP鼻息肉组织中黏膜下腺数量显著减少。在培养的鼻组织中，SLPI被转化生长因子-1（TGF-1）和白细胞介素-4（IL-4）下调，而CLU表达被TGF-1抑制。糖皮质激素治疗2周显著增加了所有下调的AMPs的表达，但不包括LYZ。此外，布地奈德显著增加了培养鼻组织中SLPI和CLU的表达。 结论：CRSwNP鼻组织中主要抗菌蛋白的表达显著降低。SLPI和CLU的表达与黏膜下腺数量相关，并受炎性细胞因子和糖皮质激素调控。
J Huazhong Univ Sci Technolog Med Sci. 2017-6
Int Arch Allergy Immunol. 2019
Front Immunol. 2024
J Inflamm Res. 2024-2-26
J Inflamm Res. 2024-2-8
J Allergy Clin Immunol. 2022-9
Clin Exp Allergy. 2019-5-29
Int Forum Allergy Rhinol. 2018-11-29
Int Forum Allergy Rhinol. 2018-10-8
Int Forum Allergy Rhinol. 2018-1-16
Clin Exp Otorhinolaryngol. 2018-6
Zotero 插件
