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The proton ATPase inhibitor bafilomycin A 1 reduces the release of rhinovirus C and cytokines from primary cultures of human nasal epithelial cells.

The proton ATPase inhibitor bafilomycin A 1 reduces the release of rhinovirus C and cytokines from primary cultures of human nasal epithelial cells.

Authors :
Yamaya M
Deng X
Kikuchi A
Sugawara M
Saito N
Kubo T
Momma H
Kawase T
Nakagome K
Shimotai Y
Nishimura H
Source :
Virus research [Virus Res] 2021 Oct 15; Vol. 304, pp. 198548. Date of Electronic Publication: 2021 Aug 21.
Publication Year :
2021

Abstract

Rhinovirus species C (RV-C) causes more severe asthma attacks than other rhinovirus species. However, the modulation of RV-C replication by drugs has not been well studied. Primary human nasal epithelial (HNE) cells cultured on filter membranes with air-liquid interface methods were infected with RV-C03, and the levels of RV-C03 RNA collected from the airway surface liquid (ASL) of HNE cells were measured with a SYBR Green assay. Pretreatment of HNE cells with the specific vacuolar H <superscript>+</superscript> -ATPase inhibitor bafilomycin A <subscript>1</subscript> reduced the RV-C03 RNA levels in the ASL; inflammatory cytokines, including interleukin (IL)-1β, IL-6 and IL-8, in the supernatant; the mRNA expression of the RV-C receptor cadherin-related family member 3 (CDHR3) in the cells; and the number of acidic endosomes where RV-B RNA enters the cytoplasm. The levels of RV-C03 RNA in the ASL obtained from HNE cells with the CDHR3 rs6967,330 G/A genotype tended to be higher than those obtained from HNE cells with the G/G genotype. Pretreatment with the Na <superscript>+</superscript> /H <superscript>+</superscript> exchanger inhibitor ethyl-isopropyl amiloride or either of the macrolides clarithromycin or EM900 also reduced RV-C03 RNA levels in the ASL and the number of acidic endosomes in HNE cells. In addition, significant levels of RV-A16, RV-B14 and RV-C25 RNA were detected in the ASL, and bafilomycin A <subscript>1</subscript> also decreased the RV-C25 RNA levels. These findings suggest that bafilomycin A <subscript>1</subscript> may reduce the release of RV-Cs and inflammatory cytokines from human airway epithelial cells. RV-Cs may be sensitive to drugs, including bafilomycin A <subscript>1</subscript> , that increase endosomal pH, and CDHR3 may mediate virus entry through receptor-mediated endocytosis in human airway epithelial cells.<br /> (Copyright © 2021. Published by Elsevier B.V.)

Details

Language :
English
ISSN :
1872-7492
Volume :
304
Database :
MEDLINE
Journal :
Virus research
Publication Type :
Academic Journal
Accession number :
34425162
Full Text :
https://doi.org/10.1016/j.virusres.2021.198548