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SARS-CoV-2 通过 ACE2 受体诱导人鼻腔上皮细胞中细胞因子和 MUC5AC/5B 的表达。

SARS-CoV-2 Induces Expression of Cytokine and MUC5AC/5B in Human Nasal Epithelial Cell through ACE 2 Receptor.

机构信息

Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Yeungnam University, Daegu, Republic of Korea.

Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, Republic of Korea.

出版信息

Biomed Res Int. 2022 Jun 2;2022:2743046. doi: 10.1155/2022/2743046. eCollection 2022.

DOI:10.1155/2022/2743046
PMID:35692597
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9184209/
Abstract

BACKGROUND

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a novel infectious respiratory disease called COVID-19, which is threatening public health worldwide. SARS-CoV-2 spike proteins connect to the angiotensin converting enzyme 2 (ACE2) receptor through the receptor binding domain and are then activated by the transmembrane protease serine subtype 2 (TMPRSS2). The ACE2 receptor is highly expressed in human nasal epithelial cells. Nasal ciliated cells are primary targets for SARS-CoV-2 replication. However, the effect of SARS-CoV-2 on the upper respiratory tract remains unknown, thus leading to the purpose of our study. We investigate the effects of SARS-CoV-2 on cytokines and mucin expression in human nasal epithelial cells.

METHODS

We investigated the effects of the SARS-CoV-2 spike protein receptor binding domain (RBD) on cytokines (IL-1, IL-6, and IL-8) and MUC5AC/5B expression via real-time PCR, ELISA, periodic acid-Schiff (PAS) staining, and immunofluorescence staining in cultured human nasal epithelial cells.

RESULTS

The mRNA expression and protein production of cytokines (IL-1, IL-6, and IL-8) and MUC5AC/5B were increased by SARS-CoV-2 spike protein RBD. ACE2 receptor inhibitor suppressed the expression of cytokines (IL-1, IL-6, and IL-8) and MUC5AC/5B induced by SARS-CoV-2 spike protein RBD.

CONCLUSIONS

SARS-CoV-2 induced cytokines (IL-1, IL-6, and IL-8) and MUC5AC/5B expression through the ACE 2 receptor in human nasal epithelial cells. Therefore, ACE2 receptor inhibitors can be an effective therapeutic option for SARS-CoV-2 infection.

摘要

背景

严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）引起一种新型传染性呼吸道疾病，称为 COVID-19，正在威胁全球公众健康。SARS-CoV-2 刺突蛋白通过受体结合域与血管紧张素转化酶 2（ACE2）受体结合，然后被跨膜丝氨酸蛋白酶 2 型（TMPRSS2）激活。ACE2 受体在人鼻上皮细胞中高度表达。鼻纤毛细胞是 SARS-CoV-2 复制的主要靶标。然而，SARS-CoV-2 对上呼吸道的影响尚不清楚，因此我们进行了这项研究。我们研究了 SARS-CoV-2 对人鼻上皮细胞中细胞因子和粘蛋白表达的影响。

方法

我们通过实时 PCR、ELISA、过碘酸-Schiff（PAS）染色和免疫荧光染色，研究了 SARS-CoV-2 刺突蛋白受体结合域（RBD）对培养的人鼻上皮细胞中细胞因子（IL-1、IL-6 和 IL-8）和 MUC5AC/5B 表达的影响。

结果

SARS-CoV-2 刺突蛋白 RBD 增加了细胞因子（IL-1、IL-6 和 IL-8）和 MUC5AC/5B 的 mRNA 表达和蛋白产生。ACE2 受体抑制剂抑制了 SARS-CoV-2 刺突蛋白 RBD 诱导的细胞因子（IL-1、IL-6 和 IL-8）和 MUC5AC/5B 的表达。

结论

SARS-CoV-2 通过人鼻上皮细胞中的 ACE2 受体诱导细胞因子（IL-1、IL-6 和 IL-8）和 MUC5AC/5B 的表达。因此，ACE2 受体抑制剂可以成为 SARS-CoV-2 感染的有效治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/96b9452f0eb9/BMRI2022-2743046.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/3a498def1c5b/BMRI2022-2743046.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/b6fdc4c90bba/BMRI2022-2743046.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/6fac8f53de69/BMRI2022-2743046.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/cccf5f1604b8/BMRI2022-2743046.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/1005041a28d9/BMRI2022-2743046.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/96b9452f0eb9/BMRI2022-2743046.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/3a498def1c5b/BMRI2022-2743046.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/b6fdc4c90bba/BMRI2022-2743046.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/6fac8f53de69/BMRI2022-2743046.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/cccf5f1604b8/BMRI2022-2743046.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/1005041a28d9/BMRI2022-2743046.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/90ea/9184209/96b9452f0eb9/BMRI2022-2743046.006.jpg

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