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10.3389/fimmu.2021.728896

http://scihub22266oqcxt.onion/10.3389/fimmu.2021.728896
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suck abstract from ncbi


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pmid34616396      Front+Immunol 2021 ; 12 (ä): 728896
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  • SARS-CoV-2 Coronavirus Spike Protein-Induced Apoptosis, Inflammatory, and Oxidative Stress Responses in THP-1-Like-Macrophages: Potential Role of Angiotensin-Converting Enzyme Inhibitor (Perindopril) #MMPMID34616396
  • Barhoumi T; Alghanem B; Shaibah H; Mansour FA; Alamri HS; Akiel MA; Alroqi F; Boudjelal M
  • Front Immunol 2021[]; 12 (ä): 728896 PMID34616396show ga
  • A purified spike (S) glycoprotein of severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) coronavirus was used to study its effects on THP-1 macrophages, peripheral blood mononuclear cells (PBMCs), and HUVEC cells. The S protein mediates the entry of SARS-CoV-2 into cells through binding to the angiotensin-converting enzyme 2 (ACE2) receptors. We measured the viability, intracellular cytokine release, oxidative stress, proinflammatory markers, and THP-1-like macrophage polarization. We observed an increase in apoptosis, ROS generation, MCP-1, and intracellular calcium expression in the THP-1 macrophages. Stimulation with the S protein polarizes the THP-1 macrophages towards proinflammatory futures with an increase in the TNFalpha and MHC-II M1-like phenotype markers. Treating the cells with an ACE inhibitor, perindopril, at 100 microM reduced apoptosis, ROS, and MHC-II expression induced by S protein. We analyzed the sensitivity of the HUVEC cells after the exposure to a conditioned media (CM) of THP-1 macrophages stimulated with the S protein. The CM induced endothelial cell apoptosis and MCP-1 expression. Treatment with perindopril reduced these effects. However, the direct stimulation of the HUVEC cells with the S protein, slightly increased HIF1alpha and MCP-1 expression, which was significantly increased by the ACE inhibitor treatment. The S protein stimulation induced ROS generation and changed the mitogenic responses of the PBMCs through the upregulation of TNFalpha and interleukin (IL)-17 cytokine expression. These effects were reduced by the perindopril (100 microM) treatment. Proteomic analysis of the S protein stimulated THP-1 macrophages with or without perindopril (100 microM) exposed more than 400 differentially regulated proteins. Our results provide a mechanistic analysis suggesting that the blood and vascular components could be activated directly through S protein systemically present in the circulation and that the activation of the local renin angiotensin system may be partially involved in this process. GRAPHICAL: Suggested pathways that might be involved at least in part in S protein inducing activation of inflammatory markers (red narrow) and angiotensin-converting enzyme inhibitor (ACEi) modulation of this process (green narrow).
  • |Angiotensin-Converting Enzyme Inhibitors/*pharmacology[MESH]
  • |Apoptosis/*drug effects[MESH]
  • |COVID-19 Drug Treatment[MESH]
  • |COVID-19/*immunology/physiopathology/virology[MESH]
  • |Cell Line[MESH]
  • |Humans[MESH]
  • |Macrophages/drug effects/*immunology[MESH]
  • |Oxidative Stress/*drug effects[MESH]
  • |Peptidyl-Dipeptidase A/genetics/immunology[MESH]
  • |Perindopril/*pharmacology[MESH]
  • |Pyroptosis/drug effects[MESH]
  • |SARS-CoV-2/genetics/*immunology[MESH]


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