Immunotoxicology Group, Department of Ecology, Institute for Biological Research "Siniša Stanković", National Institute of Republic of Serbia, University of Belgrade, 142 Bulevar Despota Stefana, 11000 Belgrade, Serbia.
Institute of Zoology, Faculty of Biology, University of Belgrade, 16 Studentski trg, 11000 Belgrade, Serbia.
Int J Mol Sci. 2024 Aug 8;25(16):8631. doi: 10.3390/ijms25168631.
The skin is a direct target of the air pollutant benzo[a]pyrene (BaP). While its carcinogenic qualities are well-studied, the immunotoxicity of BaP after dermal exposure is less understood. This study examines the immunomodulatory effects of a 10-day epicutaneous BaP application, in environmentally/occupationally relevant doses, by analyzing ex vivo skin immune response (skin explant, epidermal cells and draining lymph node/DLN cell activity), alongside the skin's reaction to sensitization with experimental hapten dinitrochlorobenzene (DNCB). The results show that BaP application disrupts the structure of the epidermal layer and promotes immune cell infiltration in the dermis. BaP exposure led to oxidative stress in epidermal cells, characterized by decreased reduced glutathione and increased AHR and Cyp1A1 expression. Production and gene expression of proinflammatory cytokines (TNF, IL-1β) by epidermal cells decreased, while IL-10 response increased. Decreased spontaneous production of IFN-γ and IL-17, along with unchanged IL-10, was observed in DLC cells, whereas ConA-stimulated production of these cytokines was elevated. Local immunosuppression caused by BaP application seems to reduce the skin's response to an additional stimulus, evidenced by decreased effector activity of DLN cells three days after sensitization with DNCB. These findings provide new insight into the immunomodulatory effects and health risks associated with skin exposure to BaP.
皮肤是空气污染物苯并[a]芘（BaP）的直接靶标。虽然其致癌特性已经得到了充分研究，但皮肤暴露于 BaP 后的免疫毒性却知之甚少。本研究通过分析体外皮肤免疫反应（皮肤标本、表皮细胞和引流淋巴结/DLN 细胞活性），以及皮肤对实验性半抗原二硝基氯苯（DNCB）致敏的反应，研究了在环境/职业相关剂量下，10 天经皮 BaP 应用的免疫调节作用。结果表明，BaP 应用会破坏表皮层的结构，并促进真皮中免疫细胞的浸润。BaP 暴露会导致表皮细胞发生氧化应激，表现为还原型谷胱甘肽减少，AHR 和 Cyp1A1 表达增加。表皮细胞产生和基因表达的促炎细胞因子（TNF、IL-1β）减少，而 IL-10 反应增加。DLC 细胞中自发产生 IFN-γ和 IL-17 的能力下降，同时 IL-10 不变，而 ConA 刺激这些细胞因子的产生增加。BaP 应用引起的局部免疫抑制似乎降低了皮肤对额外刺激的反应，这表现在 DNCB 致敏后三天，DLN 细胞的效应活性降低。这些发现为 BaP 皮肤暴露相关的免疫调节作用和健康风险提供了新的见解。
