Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In Vitro

<b>Background</b>: Although treatments using thermal water have yielded beneficial effects in respiratory tract infections, the effects of thermal water under experimental conditions similar to those triggered by SARS-CoV-2 have yet to be evaluated. This study aimed to assess whether the...

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Main Authors: Anna Scanu, Maria Chiara Maccarone, Fabrizio Caldara, Gianluca Regazzo, Roberto Luisetto, Stefano Masiero
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Biomedicines
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Online Access:https://www.mdpi.com/2227-9059/12/12/2917
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author Anna Scanu
Maria Chiara Maccarone
Fabrizio Caldara
Gianluca Regazzo
Roberto Luisetto
Stefano Masiero
author_facet Anna Scanu
Maria Chiara Maccarone
Fabrizio Caldara
Gianluca Regazzo
Roberto Luisetto
Stefano Masiero
author_sort Anna Scanu
collection DOAJ
description <b>Background</b>: Although treatments using thermal water have yielded beneficial effects in respiratory tract infections, the effects of thermal water under experimental conditions similar to those triggered by SARS-CoV-2 have yet to be evaluated. This study aimed to assess whether thermal water could interfere with the interaction between SARS-CoV-2 and host cells and influence inflammatory factors. <b>Methods</b>: Human nasal epithelial primary cells (HNEpCs) were stimulated with SARS-CoV-2 spike protein in the presence or absence of thermal water or tap water. Cell viability, cytokine concentration, ACE2 and TMPRSS2 levels, and ACE2 activity were determined in the cell cultures. <b>Results</b>: Exposure of HNEpCs to spike protein increased IL-6, IL-8, and IL-1β production, with decreased production observed in the presence of thermal water at an optimal dose. Treatment of cells with tap water did not affect cytokine release in unstimulated or spike-stimulated cells. Spike-protein-stimulated HNEpCs showed reduced levels of ACE2, which were partially restored only in the presence of thermal water. Spike protein did not affect the TMPRSS2 levels of the cell lysates. Stimulation with spike protein induced an increase in the concentration of both receptors in the supernatants, while treatment with thermal water reduced TMPRSS2 levels in both the cells and supernatants. Stimulation with spike protein increased ACE2 activity, which was reduced with thermal water. <b>Conclusions</b>: This study shows the regulatory effects of mineral-rich thermal water on spike-protein-induced pro-inflammatory cytokine production and the amount and activity of receptors mainly involved in viral entry, suggesting a potential use of this treatment as a support therapy for SARS-CoV-2 infection of the upper respiratory tract.
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spelling doaj-art-4fbf9c6ac2d84fb582bd5e0da34114742025-08-20T02:00:55ZengMDPI AGBiomedicines2227-90592024-12-011212291710.3390/biomedicines12122917Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In VitroAnna Scanu0Maria Chiara Maccarone1Fabrizio Caldara2Gianluca Regazzo3Roberto Luisetto4Stefano Masiero5Rehabilitation Unit, Department of Neuroscience-DNS, University of Padova, Via Giustiniani 2, 35128 Padova, ItalyRehabilitation Unit, Department of Neuroscience-DNS, University of Padova, Via Giustiniani 2, 35128 Padova, ItalyPietro d’Abano Thermal Studies Center, Via Jappelli 5, 35031 Abano Terme, ItalyPhysical Medicine and Rehabilitation School, University of Padova, Via Giustiniani 2, 35128 Padova, ItalyDepartment of Surgical Oncological and Gastroenterological Sciences-DISCOG, University of Padova, Via Giustiniani 2, 35128 Padova, ItalyRehabilitation Unit, Department of Neuroscience-DNS, University of Padova, Via Giustiniani 2, 35128 Padova, Italy<b>Background</b>: Although treatments using thermal water have yielded beneficial effects in respiratory tract infections, the effects of thermal water under experimental conditions similar to those triggered by SARS-CoV-2 have yet to be evaluated. This study aimed to assess whether thermal water could interfere with the interaction between SARS-CoV-2 and host cells and influence inflammatory factors. <b>Methods</b>: Human nasal epithelial primary cells (HNEpCs) were stimulated with SARS-CoV-2 spike protein in the presence or absence of thermal water or tap water. Cell viability, cytokine concentration, ACE2 and TMPRSS2 levels, and ACE2 activity were determined in the cell cultures. <b>Results</b>: Exposure of HNEpCs to spike protein increased IL-6, IL-8, and IL-1β production, with decreased production observed in the presence of thermal water at an optimal dose. Treatment of cells with tap water did not affect cytokine release in unstimulated or spike-stimulated cells. Spike-protein-stimulated HNEpCs showed reduced levels of ACE2, which were partially restored only in the presence of thermal water. Spike protein did not affect the TMPRSS2 levels of the cell lysates. Stimulation with spike protein induced an increase in the concentration of both receptors in the supernatants, while treatment with thermal water reduced TMPRSS2 levels in both the cells and supernatants. Stimulation with spike protein increased ACE2 activity, which was reduced with thermal water. <b>Conclusions</b>: This study shows the regulatory effects of mineral-rich thermal water on spike-protein-induced pro-inflammatory cytokine production and the amount and activity of receptors mainly involved in viral entry, suggesting a potential use of this treatment as a support therapy for SARS-CoV-2 infection of the upper respiratory tract.https://www.mdpi.com/2227-9059/12/12/2917SARS-CoV-2COVID-19spike proteinbalneotherapyinflammationthermal water
spellingShingle Anna Scanu
Maria Chiara Maccarone
Fabrizio Caldara
Gianluca Regazzo
Roberto Luisetto
Stefano Masiero
Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In Vitro
Biomedicines
SARS-CoV-2
COVID-19
spike protein
balneotherapy
inflammation
thermal water
title Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In Vitro
title_full Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In Vitro
title_fullStr Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In Vitro
title_full_unstemmed Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In Vitro
title_short Thermal Water Reduces the Inflammatory Process Induced by the SARS-CoV-2 Spike Protein in Human Airway Epithelial Cells In Vitro
title_sort thermal water reduces the inflammatory process induced by the sars cov 2 spike protein in human airway epithelial cells in vitro
topic SARS-CoV-2
COVID-19
spike protein
balneotherapy
inflammation
thermal water
url https://www.mdpi.com/2227-9059/12/12/2917
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