Jiang Hongjuan, Chi Xiangyu, Sun Yanhong, Li Hongwen
Department of Geriatric Respiratory Disease, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.
J Inflamm Res. 2024 Jul 8;17:4419-4429. doi: 10.2147/JIR.S470097. eCollection 2024.
Previous research indicated that vitamin D binding protein (VDBP) is an independent multifunctional protein that plays a vital role in acute inflammatory and tissue damage. However, its role in acute lung injury (ALI) due to coronavirus disease 2019 (COVID-19) is unclear, and studies are lacking. This study intends to investigate the difference in serum VDBP levels in COVID-19 patients with ALI or without ALI and further explore the role of VDBP in the inflammatory response of ALI through cellular models.
The serum was collected from COVID-19 patients, and the concentration of serum VDBP was detected. Construct a VDBP gene-silencing plasmid and transfect it into human alveolar epithelial A549 cells. After 72 hours of lipopolysaccharide (LPS) intervention, The inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were detected, and cell counting kit-8 (CCK-8) assay was used to detect cell viability. Flow cytometry was used to detect cell apoptosis.
The serum concentration of VDBP was significantly higher in COVID-19 with ALI ( < 0.05). Correlation analysis indicated serum VDBP positively correlated with leukocyte (=0.329, = 0.002), c-reaction protein ( = 0.470, < 0.001), serum amyloid A ( = 0.900, < 0.001), procalcitonin ( = 0.670, < 0.001), and interleukin 6 ( = 0.452, < 0.001). Simultaneously, the logistic regression analysis showed that increased serum VDBP was an independent risk factor for ALI in COVID-19 patients (OR 1.003 95% CI 1.001-1.006, = 0.002). In human alveolar epithelial A549 cells, after LPS intervention, the inflammatory factor IL-1β and TNF-A significantly reduced in the VDBP gene silencing group compared to the negative control (NC) group ( < 0.05). The cell viability of the VDBP gene silencing group was significantly increased compared to the NC group, and the cell apoptosis rate was significantly reduced ( < 0.05).
In COVID-19 patients, acute lung injury may lead to increased serum concentration of VDBP. VDBP plays a vital role in promoting inflammatory response and apoptosis of bronchial epithelial cells.
先前的研究表明，维生素D结合蛋白（VDBP）是一种独立的多功能蛋白，在急性炎症和组织损伤中起重要作用。然而，其在2019冠状病毒病（COVID-19）所致急性肺损伤（ALI）中的作用尚不清楚，且相关研究较少。本研究旨在调查COVID-19合并ALI或未合并ALI患者血清VDBP水平的差异，并通过细胞模型进一步探讨VDBP在ALI炎症反应中的作用。
收集COVID-19患者的血清，检测血清VDBP浓度。构建VDBP基因沉默质粒并转染至人肺泡上皮A549细胞。脂多糖（LPS）干预72小时后，检测炎症因子白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α），并采用细胞计数试剂盒-8（CCK-8）法检测细胞活力。采用流式细胞术检测细胞凋亡。
COVID-19合并ALI患者血清VDBP浓度显著升高（<0.05）。相关性分析表明，血清VDBP与白细胞（=0.329，=0.002）、C反应蛋白（=0.470，<0.001）、血清淀粉样蛋白A（=0.900，<0.001）、降钙素原（=0.670，<0.001）和白细胞介素6（=0.452，<0.001）呈正相关。同时，逻辑回归分析显示，血清VDBP升高是COVID-19患者发生ALI的独立危险因素（OR 1.003 95%CI 1.001-1.006，=0.002）。在人肺泡上皮A549细胞中，LPS干预后，VDBP基因沉默组的炎症因子IL-1β和TNF-A较阴性对照组（NC）显著降低（<0.05）。VDBP基因沉默组的细胞活力较NC组显著升高，细胞凋亡率显著降低（<0.05）。
在COVID-19患者中，急性肺损伤可能导致血清VDBP浓度升高。VDBP在促进支气管上皮细胞炎症反应和凋亡中起重要作用。
