SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis
BackgroundThe coronavirus disease (COVID-19) is a pandemic disease that threatens worldwide public health, and rheumatoid arthritis (RA) is the most common autoimmune disease. COVID-19 and RA are each strong risk factors for the other, but their molecular mechanisms are unclear. This study aims to i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1058884/full |
| _version_ | 1797988075110924288 |
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| author | Qingcong Zheng Rongjie Lin Yuchao Chen Qi Lv Jin Zhang Jingbo Zhai Weihong Xu Wanming Wang |
| author_facet | Qingcong Zheng Rongjie Lin Yuchao Chen Qi Lv Jin Zhang Jingbo Zhai Weihong Xu Wanming Wang |
| author_sort | Qingcong Zheng |
| collection | DOAJ |
| description | BackgroundThe coronavirus disease (COVID-19) is a pandemic disease that threatens worldwide public health, and rheumatoid arthritis (RA) is the most common autoimmune disease. COVID-19 and RA are each strong risk factors for the other, but their molecular mechanisms are unclear. This study aims to investigate the biomarkers between COVID-19 and RA from the mechanism of pyroptosis and find effective disease-targeting drugs.MethodsWe obtained the common gene shared by COVID-19, RA (GSE55235), and pyroptosis using bioinformatics analysis and then did the principal component analysis(PCA). The Co-genes were evaluated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ClueGO for functional enrichment, the protein-protein interaction (PPI) network was built by STRING, and the k-means machine learning algorithm was employed for cluster analysis. Modular analysis utilizing Cytoscape to identify hub genes, functional enrichment analysis with Metascape and GeneMANIA, and NetworkAnalyst for gene-drug prediction. Network pharmacology analysis was performed to identify target drug-related genes intersecting with COVID-19, RA, and pyroptosis to acquire Co-hub genes and construct transcription factor (TF)-hub genes and miRNA-hub genes networks by NetworkAnalyst. The Co-hub genes were validated using GSE55457 and GSE93272 to acquire the Key gene, and their efficacy was assessed using receiver operating curves (ROC); SPEED2 was then used to determine the upstream pathway. Immune cell infiltration was analyzed using CIBERSORT and validated by the HPA database. Molecular docking, molecular dynamics simulation, and molecular mechanics-generalized born surface area (MM-GBSA) were used to explore and validate drug-gene relationships through computer-aided drug design.ResultsCOVID-19, RA, and pyroptosis-related genes were enriched in pyroptosis and pro-inflammatory pathways(the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex, death-inducing signaling complex, regulation of interleukin production), natural immune pathways (Network map of SARS-CoV-2 signaling pathway, activation of NLRP3 inflammasome by SARS-CoV-2) and COVID-19-and RA-related cytokine storm pathways (IL, nuclear factor-kappa B (NF-κB), TNF signaling pathway and regulation of cytokine-mediated signaling). Of these, CASP1 is the most involved pathway and is closely related to minocycline. YY1, hsa-mir-429, and hsa-mir-34a-5p play an important role in the expression of CASP1. Monocytes are high-caspase-1-expressing sentinel cells. Minocycline can generate a highly stable state for biochemical activity by docking closely with the active region of caspase-1.ConclusionsCaspase-1 is a common biomarker for COVID-19, RA, and pyroptosis, and it may be an important mediator of the excessive inflammatory response induced by SARS-CoV-2 in RA patients through pyroptosis. Minocycline may counteract cytokine storm inflammation in patients with COVID-19 combined with RA by inhibiting caspase-1 expression. |
| first_indexed | 2024-04-11T07:58:29Z |
| format | Article |
| id | doaj.art-9e8e14acd8b44946b82b1c9b991d3e20 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T07:58:29Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-9e8e14acd8b44946b82b1c9b991d3e202022-12-22T04:35:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-12-011310.3389/fimmu.2022.10588841058884SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosisQingcong Zheng0Rongjie Lin1Yuchao Chen2Qi Lv3Jin Zhang4Jingbo Zhai5Weihong Xu6Wanming Wang7Department of Orthopedics, 900th Hospital of Joint Logistics Support Force, Fuzhou, ChinaDepartment of Orthopedics, 900th Hospital of Joint Logistics Support Force, Fuzhou, ChinaDepartment of Paediatrics, Fujian Provincial Hospital South Branch, Fuzhou, ChinaDepartment of Orthopedics, 900th Hospital of Joint Logistics Support Force, Fuzhou, ChinaDepartment of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, MS, United StatesKey Laboratory of Zoonose Prevention and Control at Universities of Inner Mongolia Autonomous Region, Medical College, Inner Mongolia Minzu University, Tongliao, ChinaDepartment of Orthopedics, First Affiliated Hospital of Fujian Medical University, Fuzhou, ChinaDepartment of Orthopedics, 900th Hospital of Joint Logistics Support Force, Fuzhou, ChinaBackgroundThe coronavirus disease (COVID-19) is a pandemic disease that threatens worldwide public health, and rheumatoid arthritis (RA) is the most common autoimmune disease. COVID-19 and RA are each strong risk factors for the other, but their molecular mechanisms are unclear. This study aims to investigate the biomarkers between COVID-19 and RA from the mechanism of pyroptosis and find effective disease-targeting drugs.MethodsWe obtained the common gene shared by COVID-19, RA (GSE55235), and pyroptosis using bioinformatics analysis and then did the principal component analysis(PCA). The Co-genes were evaluated by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and ClueGO for functional enrichment, the protein-protein interaction (PPI) network was built by STRING, and the k-means machine learning algorithm was employed for cluster analysis. Modular analysis utilizing Cytoscape to identify hub genes, functional enrichment analysis with Metascape and GeneMANIA, and NetworkAnalyst for gene-drug prediction. Network pharmacology analysis was performed to identify target drug-related genes intersecting with COVID-19, RA, and pyroptosis to acquire Co-hub genes and construct transcription factor (TF)-hub genes and miRNA-hub genes networks by NetworkAnalyst. The Co-hub genes were validated using GSE55457 and GSE93272 to acquire the Key gene, and their efficacy was assessed using receiver operating curves (ROC); SPEED2 was then used to determine the upstream pathway. Immune cell infiltration was analyzed using CIBERSORT and validated by the HPA database. Molecular docking, molecular dynamics simulation, and molecular mechanics-generalized born surface area (MM-GBSA) were used to explore and validate drug-gene relationships through computer-aided drug design.ResultsCOVID-19, RA, and pyroptosis-related genes were enriched in pyroptosis and pro-inflammatory pathways(the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome complex, death-inducing signaling complex, regulation of interleukin production), natural immune pathways (Network map of SARS-CoV-2 signaling pathway, activation of NLRP3 inflammasome by SARS-CoV-2) and COVID-19-and RA-related cytokine storm pathways (IL, nuclear factor-kappa B (NF-κB), TNF signaling pathway and regulation of cytokine-mediated signaling). Of these, CASP1 is the most involved pathway and is closely related to minocycline. YY1, hsa-mir-429, and hsa-mir-34a-5p play an important role in the expression of CASP1. Monocytes are high-caspase-1-expressing sentinel cells. Minocycline can generate a highly stable state for biochemical activity by docking closely with the active region of caspase-1.ConclusionsCaspase-1 is a common biomarker for COVID-19, RA, and pyroptosis, and it may be an important mediator of the excessive inflammatory response induced by SARS-CoV-2 in RA patients through pyroptosis. Minocycline may counteract cytokine storm inflammation in patients with COVID-19 combined with RA by inhibiting caspase-1 expression.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1058884/fullSARS-CoV-2COVID-19rheumatoid arthritispyroptosiscaspase-1minocycline |
| spellingShingle | Qingcong Zheng Rongjie Lin Yuchao Chen Qi Lv Jin Zhang Jingbo Zhai Weihong Xu Wanming Wang SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis Frontiers in Immunology SARS-CoV-2 COVID-19 rheumatoid arthritis pyroptosis caspase-1 minocycline |
| title | SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis |
| title_full | SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis |
| title_fullStr | SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis |
| title_full_unstemmed | SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis |
| title_short | SARS-CoV-2 induces “cytokine storm” hyperinflammatory responses in RA patients through pyroptosis |
| title_sort | sars cov 2 induces cytokine storm hyperinflammatory responses in ra patients through pyroptosis |
| topic | SARS-CoV-2 COVID-19 rheumatoid arthritis pyroptosis caspase-1 minocycline |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1058884/full |
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