Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury
Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury (COVID-19-associated KI) and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in infection-related KI by affecting t...
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Editorial Office of Journal of Shanghai Jiao Tong University (Medical Science)
2025-01-01
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| Series: | Shanghai Jiaotong Daxue xuebao. Yixue ban |
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| Online Access: | https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-1-1.shtml |
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| author | PANDIT Roshan LU Junyao HE Liheng BAO Yujie JI Ping CHEN Yingying XU Jie WANG Ying |
| author_facet | PANDIT Roshan LU Junyao HE Liheng BAO Yujie JI Ping CHEN Yingying XU Jie WANG Ying |
| author_sort | PANDIT Roshan |
| collection | DOAJ |
| description | Objective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury (COVID-19-associated KI) and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth, People′s, hospital from December 2022 to February 2023. Serum levels of inflammatory factors and chemokines were measured by using enzyme- linked immunosorbent assay (ELISA). In vitro, human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein. The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR (qRT-PCR) and ELISA. Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells (HK-2) in vitro to assess cytokine secretion. Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19, 8 (20.50%) had creatinine levels above the reference interval, which indicated the occurrence of KI. The levels of peripheral tumor necrosis factor-α (TNF-α) in the COVID-19 patient with KI group [(18.33±8.20) pg/mL] were significantly higher than those in the non-KI group [(11.88±6.50) pg/mL] (P=0.015). In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α, interleukin-1β (IL-1β) and chemokine C-X-C motif ligand 10 (CXCL10) in THP-1 macrophage cells (P<0.001). Furthermore, the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α, IL-1β and CXCL10 by HK-2 cells (P=0.005). When anti-TNF-α antibody (Infliximab) was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells, the secretion level of TNF-α by HK-2 cells decreased dramatically (P<0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI, implying the significance of TNF-α in the occurrence of COVID-19-associated KI. In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells, leading to increased inflammatory responses in renal cells, which may contribute to the development of COVID-19-associated KI. Therefore, targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI. |
| format | Article |
| id | doaj-art-1b2faa217d7f4bd683a0b7110cd6b017 |
| institution | DOAJ |
| issn | 1674-8115 |
| language | zho |
| publishDate | 2025-01-01 |
| publisher | Editorial Office of Journal of Shanghai Jiao Tong University (Medical Science) |
| record_format | Article |
| series | Shanghai Jiaotong Daxue xuebao. Yixue ban |
| spelling | doaj-art-1b2faa217d7f4bd683a0b7110cd6b0172025-08-20T03:13:03ZzhoEditorial Office of Journal of Shanghai Jiao Tong University (Medical Science)Shanghai Jiaotong Daxue xuebao. Yixue ban1674-81152025-01-0145111010.3969/j.issn.1674-8115.2025.01.0011674-8115（2025）01-0001-10Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injuryPANDIT Roshan0LU Junyao1HE Liheng2BAO Yujie3JI Ping4CHEN Yingying5XU Jie6WANG Ying7Shanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University College of Basic Medical Sciences Shanghai 200025, ChinaDepartment of Infectious Diseases, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, ChinaShanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University College of Basic Medical Sciences Shanghai 200025, ChinaDepartment of Infectious Diseases, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, ChinaShanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University College of Basic Medical Sciences Shanghai 200025, ChinaShanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University College of Basic Medical Sciences Shanghai 200025, ChinaDepartment of Infectious Diseases, Shanghai Ninth People′s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201999, ChinaShanghai Institute of Immunology, Department of Microbiology and Immunology, Shanghai Jiao Tong University College of Basic Medical Sciences Shanghai 200025, ChinaObjective·To identify relevant biomarkers for patients with coronavirus disease 2019-associated kidney injury (COVID-19-associated KI) and explore the mechanisms underlying the involvement of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) proteins in infection-related KI by affecting the interactions between renal cells and macrophages.Methods·A retrospective analysis was conducted on the clinical characteristics of COVID-19 patients with KI treated in Shanghai Ninth, People′s, hospital from December 2022 to February 2023. Serum levels of inflammatory factors and chemokines were measured by using enzyme- linked immunosorbent assay (ELISA). In vitro, human macrophage cell line THP-1 cells were stimulated with recombinant S1 subunit protein derived from SARS-CoV-2 spike protein. The cells and culture supernatants were collected to detect the levels of inflammatory factors and chemokines by using quantitative real-time PCR (qRT-PCR) and ELISA. Conditioned medium was prepared from the cell culture supernatants of S1-stimulated THP-1 cells and used to stimulate human renal epithelial cells (HK-2) in vitro to assess cytokine secretion. Antibody blocking experiments were performed to analyze the effects of the conditioned medium on the production of cytokines in HK-2 cells.Results·Among 39 patients with COVID-19, 8 (20.50%) had creatinine levels above the reference interval, which indicated the occurrence of KI. The levels of peripheral tumor necrosis factor-α (TNF-α) in the COVID-19 patient with KI group [(18.33±8.20) pg/mL] were significantly higher than those in the non-KI group [(11.88±6.50) pg/mL] (P=0.015). In vitro assay has shown that S1-spike protein stimulation promoted the level of gene transcription and production of TNF-α, interleukin-1β (IL-1β) and chemokine C-X-C motif ligand 10 (CXCL10) in THP-1 macrophage cells (P<0.001). Furthermore, the conditioned medium from S1-stimulated THP-1 cells promoted the secretion of TNF-α, IL-1β and CXCL10 by HK-2 cells (P=0.005). When anti-TNF-α antibody (Infliximab) was used to block TNF-α in the culture supernatants from S1-stimulated THP-1 cells, the secretion level of TNF-α by HK-2 cells decreased dramatically (P<0.001).Conclusion·TNF-α levels increase significantly in COVID-19 patients with KI, implying the significance of TNF-α in the occurrence of COVID-19-associated KI. In vitro experiments confirm that the S1 protein induces TNF-α secretion from THP-1 cells, leading to increased inflammatory responses in renal cells, which may contribute to the development of COVID-19-associated KI. Therefore, targeting TNF-α may become an alternative strategy to reduce the occurrence of COVID-19-associated KI.https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-1-1.shtmltumor necrosis factor-αcoronavirus disease 2019kidney injuryinflammatory responsestherapeutic target |
| spellingShingle | PANDIT Roshan LU Junyao HE Liheng BAO Yujie JI Ping CHEN Yingying XU Jie WANG Ying Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury Shanghai Jiaotong Daxue xuebao. Yixue ban tumor necrosis factor-α coronavirus disease 2019 kidney injury inflammatory responses therapeutic target |
| title | Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury |
| title_full | Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury |
| title_fullStr | Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury |
| title_full_unstemmed | Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury |
| title_short | Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury |
| title_sort | role of tumor necrosis factor α in coronavirus disease 2019 associated kidney injury |
| topic | tumor necrosis factor-α coronavirus disease 2019 kidney injury inflammatory responses therapeutic target |
| url | https://xuebao.shsmu.edu.cn/article/2025/1674-8115/1674-8115-2025-45-1-1.shtml |
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