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...
Main Authors: | , , , , , , , |
---|---|
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 |