Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

SARS-CoV-2 Spike Protein S1 Induces MG-H1/RAGE Activation to Promote Inflammation in Human Bronchial BEAS-2B Cells

Dominga Manfredelli
,
Marilena Pariano
,
Claudio Costantini
ORCID logo ,
Alessandro Graziani
,
Silvia Bozza
,
Luigina Romani
,
Paolo Puccetti
,
Vincenzo Nicola Talesa
,
Cinzia Antognelli
* ORCID logo
Version 1 : Received: 29 August 2023 / Approved: 30 August 2023 / Online: 30 August 2023 (12:02:02 CEST)

A peer-reviewed article of this Preprint also exists.

Manfredelli, D.; Pariano, M.; Costantini, C.; Graziani, A.; Bozza, S.; Romani, L.; Puccetti, P.; Talesa, V.N.; Antognelli, C. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein S1 Induces Methylglyoxal-Derived Hydroimidazolone/Receptor for Advanced Glycation End Products (MG-H1/RAGE) Activation to Promote Inflammation in Human Bronchial BEAS-2B Cells. Int. J. Mol. Sci. 2023, 24, 14868. Manfredelli, D.; Pariano, M.; Costantini, C.; Graziani, A.; Bozza, S.; Romani, L.; Puccetti, P.; Talesa, V.N.; Antognelli, C. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Spike Protein S1 Induces Methylglyoxal-Derived Hydroimidazolone/Receptor for Advanced Glycation End Products (MG-H1/RAGE) Activation to Promote Inflammation in Human Bronchial BEAS-2B Cells. Int. J. Mol. Sci. 2023, 24, 14868.

Abstract

The pathogenesis of coronavirus disease 2019 (COVID-19) is associated with a hyperinflammatory response. The mechanisms of SARS-CoV-2-induced inflammation are scantly known. Methylglyoxal (MG) is a glycolysis-derived by-product, endowed with a potent glycating action, leading to the formation of advanced glycation end products (AGEs), the major of which is MG-H1. MG-H1 exerts strong pro-inflammatory effects, frequently mediated by the receptor for AGEs (RAGE). Here, we investigated the involvement of MG-H1/RAGE axis as a potential novel mechanism in SARS-CoV-2-induced inflammation by resorting to human bronchial (BEAS-2B) and alveolar (A549) epithelial cells, expressing different levels of ACE2 receptor (R), exposed to SARS-CoV-2 spike protein 1 (S1). Interestingly, we found in BEAS-2B cells that do not express ACE2-R, that S1 exerted a pro-inflammatory action through a novel MG-H1/RAGE-based pathway. RAGE expression levels in nasopharyngeal swabs from SARS-Cov-2 positive and negative individuals, as well as glyoxalase 1 expression, the major scavenging enzyme of MG, seem to support the results obtained in vitro. Altogether, our findings reveal a novel mechanism involved in the inflammation triggered by S1, paving the way to the study of MG-H1/RAGE inflammatory axis in SARS-CoV-2 infection as a potential therapeutic target to mitigate COVID-19 associated pathogenic inflammation.

Keywords

COVID-19; SARS-CoV-2 spike protein 1 (S1); methylglyoxal; MG-H1; Glyoxalase 1; RAGE; inflammation; Nrf2; BEAS-2B; A549

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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