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)
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 bin...
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Frontiers Media S.A.
2021-09-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.728896/full |
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| author | Tlili Barhoumi Tlili Barhoumi Bandar Alghanem Bandar Alghanem Hayat Shaibah Hayat Shaibah Fatmah A. Mansour Fatmah A. Mansour Hassan S. Alamri Hassan S. Alamri Maaged A. Akiel Maaged A. Akiel Maaged A. Akiel Fayhan Alroqi Fayhan Alroqi Fayhan Alroqi Mohammad Boudjelal Mohammad Boudjelal |
| author_facet | Tlili Barhoumi Tlili Barhoumi Bandar Alghanem Bandar Alghanem Hayat Shaibah Hayat Shaibah Fatmah A. Mansour Fatmah A. Mansour Hassan S. Alamri Hassan S. Alamri Maaged A. Akiel Maaged A. Akiel Maaged A. Akiel Fayhan Alroqi Fayhan Alroqi Fayhan Alroqi Mohammad Boudjelal Mohammad Boudjelal |
| author_sort | Tlili Barhoumi |
| collection | DOAJ |
| description | 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 TNFα and MHC-II M1-like phenotype markers. Treating the cells with an ACE inhibitor, perindopril, at 100 µM 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 HIF1α 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 TNFα and interleukin (IL)-17 cytokine expression. These effects were reduced by the perindopril (100 µM) treatment. Proteomic analysis of the S protein stimulated THP-1 macrophages with or without perindopril (100 µM) 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.GraphicalSuggested 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). |
| first_indexed | 2024-12-14T00:31:36Z |
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| id | doaj.art-e06a4b62c03e4299bc97f243af6a8d65 |
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| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-14T00:31:36Z |
| publishDate | 2021-09-01 |
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| series | Frontiers in Immunology |
| spelling | doaj.art-e06a4b62c03e4299bc97f243af6a8d652022-12-21T23:24:50ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-09-011210.3389/fimmu.2021.728896728896SARS-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)Tlili Barhoumi0Tlili Barhoumi1Bandar Alghanem2Bandar Alghanem3Hayat Shaibah4Hayat Shaibah5Fatmah A. Mansour6Fatmah A. Mansour7Hassan S. Alamri8Hassan S. Alamri9Maaged A. Akiel10Maaged A. Akiel11Maaged A. Akiel12Fayhan Alroqi13Fayhan Alroqi14Fayhan Alroqi15Mohammad Boudjelal16Mohammad Boudjelal17Medical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaMedical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaMedical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaMedical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaMedical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaMedical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaDepartment of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University, Richmond, VA, United StatesMedical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaDepartment of Pediatrics, King Abdulaziz Medical City, King Abdullah Specialized Children’s Hospital, Riyadh, Saudi ArabiaMedical Research Core Facility and Platforms (MRCFP), King Abdullah International Medical Research Center/King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City (KAMC), National Guard Health Affairs (NGHA), Riyadh, Saudi ArabiaDepartment of Clinical Laboratory Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaA 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 TNFα and MHC-II M1-like phenotype markers. Treating the cells with an ACE inhibitor, perindopril, at 100 µM 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 HIF1α 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 TNFα and interleukin (IL)-17 cytokine expression. These effects were reduced by the perindopril (100 µM) treatment. Proteomic analysis of the S protein stimulated THP-1 macrophages with or without perindopril (100 µM) 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.GraphicalSuggested 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).https://www.frontiersin.org/articles/10.3389/fimmu.2021.728896/fullSARS-CoV-2spike proteinmonocyte/macrophagesinflammationangiotensin-converting enzyme inhibitorROS |
| spellingShingle | Tlili Barhoumi Tlili Barhoumi Bandar Alghanem Bandar Alghanem Hayat Shaibah Hayat Shaibah Fatmah A. Mansour Fatmah A. Mansour Hassan S. Alamri Hassan S. Alamri Maaged A. Akiel Maaged A. Akiel Maaged A. Akiel Fayhan Alroqi Fayhan Alroqi Fayhan Alroqi Mohammad Boudjelal Mohammad Boudjelal 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) Frontiers in Immunology SARS-CoV-2 spike protein monocyte/macrophages inflammation angiotensin-converting enzyme inhibitor ROS |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | SARS-CoV-2 spike protein monocyte/macrophages inflammation angiotensin-converting enzyme inhibitor ROS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.728896/full |
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