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Trichloroethylene (TCE) is a volatile, colorless liquid that is widely used as a chlorinated organic vehicle in industrial production and processing industries. Many workers exposed to trichloroethylene may develop trichloroethylene hypersensitivity syndrome (THS). However, the underlying mechanism of THS is still unclear, especially liver injury. The present study aimed to investigate whether Wnt5a/c-Jun N-terminal kinase (JNK) is involved in and regulates liver injury caused by TCE exposure and to provide new directions for the prevention and treatment in clinical settings of liver injury caused by TCE exposure. We used 6- to 8-week-old SPF-grade BALB/c female mice to establish a TCE sensitization model and explored the mechanism through inhibitor intervention. We found that the expression of Wnt5a/JNK was significantly elevated in the liver of TCE sensitization-positive mice. Inhibitors of Wnt Production 2 (IWP-2) are known antagonists of the Wnt pathway. TCE-sensitization mice treated with IWP-2 showed downregulated Wnt5a/JNK expression, reduced Kupffer cell activation, and decreased liver injury. At the same time, we found that phosphorylated JNK in TCE-sensitization mouse livers and extracted Kupffer cells showed a significant downward trend after inhibition of Wnt5a function. We also found that a specific JNK inhibitor, SP600125, decreased the secretion of cytokines and chemokines and decreased Kupffer cell activation. We demonstrated that Wnt5a/JNK was involved in the regulation of liver injury in TCE-sensitization mice and that it exacerbated liver injury by activating Kupffer cells and releasing chemokines. We therefore hypothesized that Kupffer cell activation was affected by JNK, which reduced chemokine and cytokine secretion and attenuated liver injury in TCE-sensitization mice., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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 3 ), the expression of these proteins and mRNA was significantly reduced. This phenomenon indicates that GdCl 3 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.