The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells

Contact between SARS-CoV-2 and human lung cells involves the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, the latter being strongly involved in the regulation of inflammation as well as blood pressure homeostasis. SARS-CoV-2 infection is char...

Full description

Bibliographic Details
Main Authors: Clementina Sansone, Luigi Pistelli, Angelo Del Mondo, Luana Calabrone, Angelo Fontana, Douglas M. Noonan, Adriana Albini, Christophe Brunet
Format: Article
Language:English
Published: MDPI AG 2022-08-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/11/8/1515
_version_ 1797439858582487040
author Clementina Sansone
Luigi Pistelli
Angelo Del Mondo
Luana Calabrone
Angelo Fontana
Douglas M. Noonan
Adriana Albini
Christophe Brunet
author_facet Clementina Sansone
Luigi Pistelli
Angelo Del Mondo
Luana Calabrone
Angelo Fontana
Douglas M. Noonan
Adriana Albini
Christophe Brunet
author_sort Clementina Sansone
collection DOAJ
description Contact between SARS-CoV-2 and human lung cells involves the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, the latter being strongly involved in the regulation of inflammation as well as blood pressure homeostasis. SARS-CoV-2 infection is characterized by a strong inflammatory response defined as a “cytokine storm”. Among recent therapeutic approaches against SARS-CoV-2 targeting the dramatic inflammatory reaction, some natural products are promising. Diatoms are microalgae able to produce bioactive secondary metabolites, such as the xanthophyll diatoxanthin (Dt). The aim of this study is to demonstrate the anti-inflammatory effects of Dt on the A549-hACE2 lung cell line, exploring its interaction with the ACE2 receptor, as well as depicting its role in inhibiting a cytokine storm induced by the SARS-CoV-2 spike glycoprotein. Results showed that Dt enhanced the cell metabolism, e.g., the percent of metabolically active cells, as well as the ACE2 enzymatic activity. Moreover, Dt strongly affected the response of the SARS-CoV-2 spike glycoprotein-exposed A549-hACE2 cells in decreasing the interleukin-6 production and increasing the interleukin-10 release. Moreover, Dt upregulated genes encoding for the interferon pathway related to antiviral defense and enhanced proteins belonging to the innate immunity response. The potential interest of Dt as a new therapeutic agent in the treatment and/or prevention of the severe inflammatory syndrome related to SARS-CoV-2 infection is postulated.
first_indexed 2024-03-09T11:58:46Z
format Article
id doaj.art-9ebc352f30dd42febe0fd5d09afa4065
institution Directory Open Access Journal
issn 2076-3921
language English
last_indexed 2024-03-09T11:58:46Z
publishDate 2022-08-01
publisher MDPI AG
record_format Article
series Antioxidants
spelling doaj.art-9ebc352f30dd42febe0fd5d09afa40652023-11-30T23:06:05ZengMDPI AGAntioxidants2076-39212022-08-01118151510.3390/antiox11081515The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung CellsClementina Sansone0Luigi Pistelli1Angelo Del Mondo2Luana Calabrone3Angelo Fontana4Douglas M. Noonan5Adriana Albini6Christophe Brunet7Stazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, ItalyStazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, ItalyStazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, ItalyStazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, ItalyInstitute of Biomolecular Chemistry, CNR, Via Campi Flegrei 34, Pozzuoli, 80078 Napoli, ItalyUnit of Molecular Pathology, Biochemistry and Immunology, IRCCS MultiMedica, 20138 Milan, ItalyIRCCS European Institute of Oncology, IEO, 20141 Milan, ItalyStazione Zoologica Anton Dohrn, sede Molosiglio Marina Acton, Via Ammiraglio F. Acton 55, 80133 Napoli, ItalyContact between SARS-CoV-2 and human lung cells involves the viral spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor on epithelial cells, the latter being strongly involved in the regulation of inflammation as well as blood pressure homeostasis. SARS-CoV-2 infection is characterized by a strong inflammatory response defined as a “cytokine storm”. Among recent therapeutic approaches against SARS-CoV-2 targeting the dramatic inflammatory reaction, some natural products are promising. Diatoms are microalgae able to produce bioactive secondary metabolites, such as the xanthophyll diatoxanthin (Dt). The aim of this study is to demonstrate the anti-inflammatory effects of Dt on the A549-hACE2 lung cell line, exploring its interaction with the ACE2 receptor, as well as depicting its role in inhibiting a cytokine storm induced by the SARS-CoV-2 spike glycoprotein. Results showed that Dt enhanced the cell metabolism, e.g., the percent of metabolically active cells, as well as the ACE2 enzymatic activity. Moreover, Dt strongly affected the response of the SARS-CoV-2 spike glycoprotein-exposed A549-hACE2 cells in decreasing the interleukin-6 production and increasing the interleukin-10 release. Moreover, Dt upregulated genes encoding for the interferon pathway related to antiviral defense and enhanced proteins belonging to the innate immunity response. The potential interest of Dt as a new therapeutic agent in the treatment and/or prevention of the severe inflammatory syndrome related to SARS-CoV-2 infection is postulated.https://www.mdpi.com/2076-3921/11/8/1515carotenoidsACE2COVID-19inflammationcytokineantiviral
spellingShingle Clementina Sansone
Luigi Pistelli
Angelo Del Mondo
Luana Calabrone
Angelo Fontana
Douglas M. Noonan
Adriana Albini
Christophe Brunet
The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells
Antioxidants
carotenoids
ACE2
COVID-19
inflammation
cytokine
antiviral
title The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells
title_full The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells
title_fullStr The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells
title_full_unstemmed The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells
title_short The Microalgal Diatoxanthin Inflects the Cytokine Storm in SARS-CoV-2 Stimulated ACE2 Overexpressing Lung Cells
title_sort microalgal diatoxanthin inflects the cytokine storm in sars cov 2 stimulated ace2 overexpressing lung cells
topic carotenoids
ACE2
COVID-19
inflammation
cytokine
antiviral
url https://www.mdpi.com/2076-3921/11/8/1515
work_keys_str_mv AT clementinasansone themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT luigipistelli themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT angelodelmondo themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT luanacalabrone themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT angelofontana themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT douglasmnoonan themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT adrianaalbini themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT christophebrunet themicroalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT clementinasansone microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT luigipistelli microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT angelodelmondo microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT luanacalabrone microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT angelofontana microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT douglasmnoonan microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT adrianaalbini microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells
AT christophebrunet microalgaldiatoxanthininflectsthecytokinestorminsarscov2stimulatedace2overexpressinglungcells