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.
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.
Biology and Life Sciences, Immunology and Microbiology
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