上海交通大学学报（医学版）2025，Vol.45Issue(1)：1-10,10.DOI:10.3969/j.issn.1674-8115.2025.01.001
肿瘤坏死因子-α在新型冠状病毒感染合并肾损伤中的作用
Role of tumor necrosis factor-α in coronavirus disease 2019-associated kidney injury
摘要
Abstract
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.关键词
肿瘤坏死因子-α/新型冠状病毒感染/肾损伤/炎症反应/干预靶点Key words
tumor necrosis factor-α/coronavirus disease 2019/kidney injury/inflammatory responses/therapeutic target分类
医药卫生引用本文复制引用
PANDIT Roshan,卢君瑶,何立珩,包玉洁,季萍,陈颖盈,许洁,王颖..肿瘤坏死因子-α在新型冠状病毒感染合并肾损伤中的作用[J].上海交通大学学报（医学版）,2025,45(1):1-10,10.基金项目
国家重点研发计划(2021YFC2301502,2024YFC3044400) （2021YFC2301502,2024YFC3044400）
上海交通大学"交大之星"计划医工交叉研究基金(YG2023ZD02) （YG2023ZD02）
市级医院临床管理优化项目(SHDC22021207). National Key Research and Development Program of China(2021YFC2301502,2024YFC3044400) （SHDC22021207）
the Fundamental Research Funds for the Central Universities(YG2023ZD02) （YG2023ZD02）
Municipal Hospital Clinical Management Optimization Project(SHDC22021207). （SHDC22021207）
