Department of Occupational Health, School of Public Health, Harbin Medical University, 157 Baojian Road, Harbin, 150086, Heilongjiang Province, People's Republic of China.
School of Medicine and Health, Harbin Institute of Technology, Harbin, 150001, Heilongjiang Province, People's Republic of China.
Cell Biochem Biophys. 2024 Jun;82(2):1121-1134. doi: 10.1007/s12013-024-01263-3. Epub 2024 Apr 8.
Nickel (Ni), a ductile and hard silver-white transition metal, is commonly found in occupational environments and can harm the human body. Since it is a toxic compound, long-term Ni exposure can cause pneumonia, rhinitis, and other types of respiratory inflammatory diseases. Resveratrol (Res) is a plant antitoxin polyphenol, which also has anti-cancer and anti-inflammatory properties. In this report, the toxicity of Ni-refining fumes on the human lung bronchial epithelial (BEAS-2B) cells, as well as the protective effects of Res were investigated in vitro, and the specific mechanism of its anti-inflammatory effect was explained. The experimental observations of this study revealed that Ni-refining fumes induce BEAS-2B cell damage, increase reactive oxygen species (ROS) content, activate NLRP3 (LRR-, NOD-, and pyrin domain-containing 3) inflammasome, and promote the secretion of the cytokine Interleukin (IL)-1β, leading to cellular inflammation and reducing cell activity. Resveratrol (20 μmol/L) activated sirtuin 1 (SIRT1) in BEAS-2B cells to increase protein and mRNA expression. SIRT1 was observed to inhibit the transcriptional activity of nuclear factor-kappaB (NF-κB), reduced the expression of NLRP3 protein and mRNA, and inhibited NLRP3 inflammation. The level of inflammasome activation and IL-1β overexpression could reduce the inflammatory damage caused by the Ni-refining fume particles on the BEAS-2B cells and exert anti-inflammatory protective effects. In vivo experiments further confirmed that resveratrol could effectively alleviate the acute inflammatory injuries caused due to exposure to the Ni-refining fume particles in the lung tissues of the Wistar rats, and verified that resveratrol could exert its anti-inflammatory impact through the SIRT1-NF-κB-NLRP3 pathway. These results provide an important theoretical basis for developing novel protective drugs and investigating the mechanism of action for inflammatory injury in occupational populations caused by exposure to nickel and other heavy metals.
镍（Ni）是一种具有延展性和硬度的银白色过渡金属，通常存在于职业环境中，会对人体造成伤害。由于镍是一种有毒化合物，长期暴露于镍会导致肺炎、鼻炎和其他类型的呼吸道炎症性疾病。白藜芦醇（Res）是一种植物抗毒素多酚，具有抗癌和抗炎特性。在本报告中，体外研究了镍精炼烟雾对人肺支气管上皮（BEAS-2B）细胞的毒性以及白藜芦醇的保护作用，并解释了其抗炎作用的具体机制。本研究的实验观察结果表明，镍精炼烟雾会诱导 BEAS-2B 细胞损伤，增加活性氧（ROS）含量，激活 NLRP3（富含亮氨酸重复序列、NOD 样受体和 pyrin 结构域的 3）炎症小体，并促进细胞因子白细胞介素（IL）-1β的分泌，导致细胞炎症和细胞活性降低。白藜芦醇（20μmol/L）激活了 BEAS-2B 细胞中的沉默调节蛋白 1（SIRT1），增加了蛋白质和 mRNA 的表达。观察到 SIRT1 抑制核因子-κB（NF-κB）的转录活性，降低 NLRP3 蛋白和 mRNA 的表达，并抑制 NLRP3 炎症。炎症小体激活水平和 IL-1β过表达可降低镍精炼烟尘颗粒对 BEAS-2B 细胞造成的炎症损伤，发挥抗炎保护作用。体内实验进一步证实，白藜芦醇可有效缓解 Wistar 大鼠肺组织中镍精炼烟尘颗粒引起的急性炎症损伤，并验证了白藜芦醇可通过 SIRT1-NF-κB-NLRP3 途径发挥抗炎作用。这些结果为开发新型保护药物和研究职业人群因暴露于镍和其他重金属引起的炎症损伤的作用机制提供了重要的理论依据。
