Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells

Nakazono, Akira; Nakamaru, Yuji; Ramezanpour, Mahnaz; Kondo, Takeshi; Watanabe, Masashi; Hatakeyama, Shigetsugu; Kimura, Shogo; Honma, Aya; Wormald, P. J.; Vreugde, Sarah; Suzuki, Masanobu; Homma, Akihiro

Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells

Nakazono, Akira; Nakamaru, Yuji; Ramezanpour, Mahnaz et al.

Frontiers in Cellular and Infection Microbiology, 2021, 11, 655666

Permalink : https://hdl.handle.net/2115/82010

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アクセス権	open access
URI	https://hdl.handle.net/2115/82010
タイトル	Fluticasone Propionate Suppresses Poly(I:C)-Induced ACE2 in Primary Human Nasal Epithelial Cells
著者	Nakazono, Akira ; Nakamaru, Yuji ; Ramezanpour, Mahnaz ; Kondo, Takeshi ; Watanabe, Masashi ; Hatakeyama, Shigetsugu ; Kimura, Shogo ; Honma, Aya ; Wormald, P. J. ; Vreugde, Sarah ; Suzuki, Masanobu ; Homma, Akihiro
著者名 Nakazono, Akira
著者名 Nakamaru, Yuji
著者名 Ramezanpour, Mahnaz
著者名 Kondo, Takeshi
著者名 Watanabe, Masashi
著者名 Hatakeyama, Shigetsugu
著者名 Kimura, Shogo
著者名 Honma, Aya
著者名 Wormald, P. J.
著者名 Vreugde, Sarah
e-Rad_Researcher 70455658 著者名 Suzuki, Masanobu
e-Rad_Researcher 30312359 著者名 Homma, Akihiro
言語	英語
キーワード	SARS-CoV-2
	TMPRSS2
	virus infection
	toll-like receptors
	intranasal steroid spray
	NFκ
	B
	interferon
	COVID-19
発行日	2021-04-26
出版者	Frontiers Media
収録物名	Frontiers in Cellular and Infection Microbiology
巻(号)	11
ページ	655666
抄録	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.
資源タイプ	学術雑誌論文
出版タイプ	Version of Record
PISSN	2235-2988
関連情報 (isIdenticalTo)	出版社版DOI https://doi.org/10.3389/fcimb.2021.655666