Abstract
Trichloroethylene hypersensitivity syndrome (THS), referred to as occupational medicamentosa-like dermatitis (OMDT) in China, typically manifests several days after exposure to trichloroethylene (TCE) in certain workers. Although our previous research has demonstrated that poly I:C exacerbates TCE-caused hepatitis in mice, the crucial role of poly I:C in THS renal injury remains largely unknown. In the current study, we focus on renal endothelial cell (EC) dysfunction after poly I:C treatment using a TCE-sensitized mouse model. Renal injury was evaluated in mice pretreated with poly I:C and compared to those without pretreatment, and the acetylation of high-mobility group box protein 1 (HMGB1) was also examined. Our results demonstrated that pretreatment with poly I:C worsened TCE-caused histological damage and functional impairment of mice kidneys. Notably, renal EC injury was identified as a key contributor to kidney damage, with poly I:C pretreatment amplifying these effects in the context of TCE sensitization. Moreover, our data showed that poly I:C, through its interaction with toll-like receptor 3 (TLR3), enhanced HMGB1 acetylation and subsequent release from renal ECs. Therefore, these key findings highlight a distinctive role of poly I:C in exacerbating TCE-caused renal EC injury. This study sheds new light on the complex interplay between viral mimicry and chemical sensitization, offering potential mechanistic explanations for THS pathogenesis. Our findings may help shape advanced strategies to prevent viral infections and address renal damage related to TCE exposure, with implications for clinical practice.