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SerpinB3/B4 抑制慢性鼻息肉鼻窦炎中上皮细胞衍生的 CXCL8/IL-8 表达。

SerpinB3/B4 Abates Epithelial Cell-Derived CXCL8/IL-8 Expression in Chronic Rhinosinusitis with Nasal Polyps.

机构信息

Department of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China.

Beijing Key Laboratory of Nasal Diseases, Beijing Laboratory of Allergic Diseases, Beijing Institute of Otolaryngology, Beijing 100005, China.

出版信息

J Immunol Res. 2024 Mar 21;2024:8553447. doi: 10.1155/2024/8553447. eCollection 2024.

DOI:10.1155/2024/8553447
PMID:38550710
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10978078/
Abstract

BACKGROUND

Serine proteinase inhibitors, clade B, member 3 (SerpinB3) and B4 are highly similar in amino acid sequences and associated with inflammation regulation. We investigated SerpinB3 and B4 expression and their roles in chronic rhinosinusitis with nasal polyps (CRSwNP).

METHODS

The expression of SerpinB3 and B4 in nasal mucosa tissues, brush cells, and secretions from CRSwNP patients was measured, and their regulation by inflammatory cytokines were investigated. Their functions were also analyzed using air-liquid interface (ALI)-cultured primary human nasal epithelial cells (HNECs) and transcriptomic analysis.

RESULTS

Both SerpinB3 and B4 expression was higher in nasal mucosa, brush cells, and secretions from eosinophilic (E) CRSwNP and nonECRSwNP patients than in healthy controls. Immunofluorescence staining indicated that SerpinB3 and B4 were primarily expressed in epithelial cells and their expression was higher in CRSwNP patients. SerpinB3 and B4 expression was upregulated by interleukin-4 (IL-4), IL-5, IL-6, and IL-17a. Transcriptomic analysis identified differentially expressed genes (DEGs) in response to recombinant SerpinB3 and B4 stimulation. Both the DEGs of SerpinB3 and B4 were associated with disease genes of nasal polyps and inflammation in DisGeNET database. Pathway enrichment indicated that downregulated DEGs of SerpinB3 and B4 were both enriched in cytokine-cytokine receptor interactions, with CXCL8 as the hub gene in the protein-protein interaction networks. Furthermore, CXCL8/IL-8 expression was downregulated by recombinant SerpinB3 and B4 protein in ALI-cultured HNECs, and upregulated when knockdown of SerpinB3/B4.

CONCLUSION

SerpinB3/B4 expression is upregulated in nasal mucosa of CRSwNP patients. SerpinB3/B4 may play an anti-inflammatory role in CRSwNP by inhibiting the expression of epithelial cell-derived CXCL8/IL-8.

摘要

背景

丝氨酸蛋白酶抑制剂 B3 亚家族成员 3（SerpinB3）和 B4 在氨基酸序列上高度相似，与炎症调节有关。我们研究了 SerpinB3 和 B4 在慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）中的表达及其作用。

方法

测量了 SerpinB3 和 B4 在鼻黏膜组织、刷状细胞和 CRSwNP 患者分泌物中的表达，并研究了炎症细胞因子对其的调节作用。还使用气液界面（ALI）培养的原代人鼻上皮细胞（HNECs）和转录组分析分析了它们的功能。

结果

嗜酸性粒细胞（E）CRSwNP 和非 ECRSwNP 患者的鼻黏膜、刷状细胞和分泌物中 SerpinB3 和 B4 的表达均高于健康对照组。免疫荧光染色表明 SerpinB3 和 B4 主要在上皮细胞中表达，在 CRSwNP 患者中表达更高。白细胞介素-4（IL-4）、IL-5、IL-6 和 IL-17a 上调了 SerpinB3 和 B4 的表达。转录组分析鉴定了重组 SerpinB3 和 B4 刺激后差异表达的基因（DEGs）。SerpinB3 和 B4 的 DEGs 均与 DisGeNET 数据库中鼻息肉和炎症的疾病基因相关。通路富集表明，SerpinB3 和 B4 的下调 DEGs 均富集在细胞因子-细胞因子受体相互作用中，CXCL8 是蛋白质-蛋白质相互作用网络中的枢纽基因。此外，重组 SerpinB3 和 B4 蛋白在 ALI 培养的 HNECs 中下调了 CXCL8/IL-8 的表达，而在 SerpinB3/B4 敲低时则上调了 CXCL8/IL-8 的表达。

结论

CRSwNP 患者鼻黏膜中 SerpinB3/B4 的表达上调。SerpinB3/B4 可能通过抑制上皮细胞衍生的 CXCL8/IL-8 的表达在 CRSwNP 中发挥抗炎作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/7ccaf0b39c2b/JIR2024-8553447.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/7d7a7910b55d/JIR2024-8553447.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/28910ed94551/JIR2024-8553447.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/e2c142a7a25b/JIR2024-8553447.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/551ddc07f4bb/JIR2024-8553447.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/f64df99c5689/JIR2024-8553447.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/7ccaf0b39c2b/JIR2024-8553447.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/7d7a7910b55d/JIR2024-8553447.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/28910ed94551/JIR2024-8553447.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/e2c142a7a25b/JIR2024-8553447.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/551ddc07f4bb/JIR2024-8553447.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/f64df99c5689/JIR2024-8553447.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f50d/10978078/7ccaf0b39c2b/JIR2024-8553447.006.jpg

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