Work

Cytokines from Macrophages Activated by Spike S1 of SARS-CoV-2 Cause eNOS/Arginase Imbalance in Endothelial Cells

Year: 2025

Type: article

Abstract: Multiple lines of evidence suggest that endothelial dysfunction is a key player in the pathogenesis of COVID-19, with cytokine storm as one of the main primary causes. Among the mechanisms underlying endothelial damage, clinical findings identify alterations in arginine metabolism, as patients with severe COVID-19 exhibit lower levels of nitric oxide synthase (eNOS) and upregulated arginase. In this study, we investigated, in human endothelial cells (HUVECs), the effect of conditioned medium from macrophages activated with SARS-CoV-2 Spike protein (CM_S1) on arginine metabolism. The results indicate that CM_S1 causes a marked decrease in eNOS and an increase in arginase, along with a greater intracellular arginine content and the induction of the CAT2 transporter. These effects are ascribable to the inflammatory mediators released by macrophages in CM_S1, mainly TNFα and IL-1β. Since infliximab, an antibody targeting TNFα, and baricitinib, an inhibitor of the JAK/STAT pathway, correct the observed imbalance between eNOS and arginase, our findings suggest the potential efficacy of a combined therapy to counteract endothelial dysfunction in COVID-19.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms26125916

Authors: Giulia Recchia Luciani, Rossana Visigalli, Valeria Dall’Asta, Bianca Maria Rotoli, Amelia Barilli

Institution: University of Parma

Language: English

Topic: Nitric Oxide and Endothelin Effects

Subfield: Physiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,499