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

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

doi:10.3389/fcimb.2021.655666

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

Front Cell Infect Microbiol. 2021 Apr 26:11:655666. doi: 10.3389/fcimb.2021.655666. eCollection 2021.

Affiliations

¹ Department of Otolaryngology-Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
² Department of Surgery-Otorhinolaryngology Head and Neck Surgery, Central Adelaide Local Health Network and the University of Adelaide, Adelaide, SA, Australia.
³ Department of Biochemistry, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.

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.

Keywords: COVID-19; NFκB; SARS-CoV-2; TMPRSS2; interferon; intranasal steroid spray; toll-like receptors; virus infection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiotensin-Converting Enzyme 2
COVID-19*
Epithelial Cells
Fluticasone
Humans
Peptidyl-Dipeptidase A* / genetics
RNA, Viral
SARS-CoV-2

Substances

RNA, Viral
Fluticasone
Peptidyl-Dipeptidase A
Angiotensin-Converting Enzyme 2