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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells
| Title: | Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells |
| Authors: | Nakazono, Akira Browse this author | | Nakamaru, Yuji Browse this author | | Ramezanpour, Mahnaz Browse this author | | Kondo, Takeshi Browse this author | | Watanabe, Masashi Browse this author | | Hatakeyama, Shigetsugu Browse this author | | Kimura, Shogo Browse this author | | Honma, Aya Browse this author | | Wormald, P. J. Browse this author | | Vreugde, Sarah Browse this author | | Suzuki, Masanobu Browse this author →KAKEN DB | | Homma, Akihiro Browse this author →KAKEN DB |
| Keywords: | SARS-CoV-2 | | TMPRSS2 | | virus infection | | toll-like receptors | | intranasal steroid spray | | NFκ | | B | | interferon | | COVID-19 |
| Issue Date: | 26-Apr-2021 |
| Publisher: | Frontiers Media |
| Journal Title: | Frontiers in Cellular and Infection Microbiology |
| Volume: | 11 |
| Start Page: | 655666 |
| Publisher DOI: | 10.3389/fcimb.2021.655666 |
| Abstract: | Background From the first detection in 2019, SARS-CoV-2 infections have spread rapidly worldwide and have been proven to cause an urgent and important health problem. SARS-CoV-2 cell entry depends on two proteins present on the surface of host cells, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2). The nasal cavity is thought to be one of the initial sites of infection and a possible reservoir for dissemination within and between individuals. However, it is not known how the expression of these genes is regulated in the nasal mucosa. Objective In this study, we examined whether the expression of ACE2 and TMPRSS2 is affected by innate immune signals in the nasal mucosa. We also investigated how fluticasone propionate (FP), a corticosteroid used as an intranasal steroid spray, affects the gene expression. Methods Primary human nasal epithelial cells (HNECs) were collected from the nasal mucosa and incubated with Toll-like receptor (TLR) agonists and/or fluticasone propionate (FP), followed by quantitative PCR, immunofluorescence, and immunoblot analyses. Results Among the TLR agonists, the TLR3 agonist Poly(I:C) significantly increased ACE2 and TMPRSS2 mRNA expression in HNECs (ACE2 36.212 +/- 11.600-fold change, p<0.0001; TMPRSS2 5.598 +/- 2.434-fold change, p=0.031). The ACE2 protein level was also increased with Poly(I:C) stimulation (2.884 +/- 0.505-fold change, p=0.003). The Poly(I:C)-induced ACE2 expression was suppressed by co-incubation with FP (0.405 +/- 0.312-fold change, p=0.044). Conclusion The activation of innate immune signals via TLR3 promotes the expression of genes related to SARS-CoV2 cell entry in the nasal mucosa, although this expression is suppressed in the presence of FP. Further studies are required to evaluate whether FP suppresses SARS-CoV-2 viral cell entry. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/82010 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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