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-β1 and IL-4 in cultured nasal tissues in vitro, while CLU expression was inhibited by TGF-β1. 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.

中文翻译：

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慢性鼻窦炎伴鼻息肉中抗菌蛋白分泌性白细胞蛋白酶抑制剂和凝聚素的表达降低

简介。抗菌肽和蛋白质 (AMP) 构成了抵御气道中病原微生物的第一道防线。AMP 与慢性鼻窦炎伴鼻息肉 (CRSwNP) 之间的关联需要进一步研究。本研究旨在调查 CRSwNP 鼻粘膜中主要失调 AMP 的表达和调节。方法。使用 RNA 测序分析了嗜酸性 (E) CRSwNP 和非 ECRSwNP 患者和健康受试者的鼻组织中 AMP 的表达。通过实时PCR验证了在CRSwNP患者中差异表达的10个最丰富的AMP，其中进一步研究了分泌性白细胞蛋白酶抑制剂（SLPI）和凝聚素（CLU）的表达和调节。结果. 与健康对照相比，CRSwNP 中 10 种最丰富的 AMP 表达差异，无论亚型如何，包括下调的 BPIFA1、BPIFB1、BPIFB2、CLU、LTF、LYZ 和 SLPI，以及上调的 S100A8、S100A9 和 HIST1H2BC。ELISA 和免疫荧光证实 CRSwNP 中 SLPI 和 CLU 水平的表达降低。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，与对照组的鼻组织相比，CRSwNP 的鼻息肉组织中黏膜下腺的数量显着减少。SLPI 在培养的鼻组织中被 TGF- β1和 IL-4下调在体外，CLU 表达被 TGF- β1抑制。糖皮质激素治疗 2 周显着增加了所有下调的 AMPs 的表达，但不增加 LYZ。此外，布地奈德显着增加了培养的鼻组织中 SLPI 和 CLU 的表达。结论。CRSwNP鼻组织中主要抗菌蛋白的表达显着降低。SLPI和CLU的表达与黏膜下腺的数量相关，并受炎性细胞因子和糖皮质激素的调节。