Department of Occupational Health and Environmental Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Key Laboratory of Dermatology (Anhui Medical University), Ministry of Education, Hefei, Anhui, China.
Toxicol Ind Health. 2023 Sep;39(9):515-527. doi: 10.1177/07482337231189605. Epub 2023 Jul 14.
Trichloroethylene (TCE) is a metal detergent commonly used in industry that can enter the human body through the respiratory tract and skin, causing occupational medicamentosa-like dermatitis due to TCE (OMDT) and multiple organ damage, including liver failure. However, the pathogenesis of liver injury remains unclear. Kupffer cells (KCs) are important tissue macrophages in the body because the polarization of KCs plays a crucial role in immune-mediated liver injury. However, the mechanism of KCs polarization in TCE-induced immune liver injury has not been thoroughly elucidated. In this study, we investigated the effect of TCE-induced KCs polarization on liver function and signal transduction pathways using the TCE sensitization model developed by our group. BALB/c mouse skin was exposed to TCE for sensitization, and an increase in the expression of M1 macrophage-specific markers (CD16/CD32, iNOS), M1 macrophage-specific cytokines IL-1β, and IFN-γ, P-JAK-1 and P-STAT1 levels were also found to be dramatically increased. When using low doses of gadolinium trichloride (GdCl), the expression of these proteins and mRNA was significantly reduced. This phenomenon indicates that GdCl blocks TCE-induced polarization of KCs and suggests that the IFN-γ/STAT1 signaling pathway may be involved in the polarization process of KCs. These findings clarify the relationship between the polarization of KCs and immune liver injury and highlight the importance of further study of immune-mediated liver injury in TCE-sensitized mice.
三氯乙烯（TCE）是一种常用于工业的金属清洁剂，可通过呼吸道和皮肤进入人体，导致 TCE（OMDT）引起的职业性药物样皮炎和多器官损伤，包括肝功能衰竭。然而，肝损伤的发病机制尚不清楚。Kupffer 细胞（KCs）是体内重要的组织巨噬细胞，因为 KCs 的极化在免疫介导的肝损伤中起着至关重要的作用。然而，TCE 诱导的免疫性肝损伤中 KCs 极化的机制尚未得到充分阐明。在这项研究中，我们使用我们小组开发的 TCE 致敏模型，研究了 TCE 诱导的 KCs 极化对肝功能和信号转导通路的影响。BALB/c 小鼠皮肤暴露于 TCE 中进行致敏，并且还发现 M1 巨噬细胞特异性标志物（CD16/CD32、iNOS）、M1 巨噬细胞特异性细胞因子 IL-1β 和 IFN-γ、P-JAK-1 和 P-STAT1 水平的表达显著增加。当使用低剂量的三氯化钆（GdCl）时，这些蛋白质和 mRNA 的表达明显降低。这一现象表明 GdCl 阻断了 TCE 诱导的 KCs 极化，提示 IFN-γ/STAT1 信号通路可能参与了 KCs 的极化过程。这些发现阐明了 KCs 的极化与免疫性肝损伤之间的关系，并强调了进一步研究 TCE 致敏小鼠免疫介导的肝损伤的重要性。
