Viral mimic polyinosine-polycytidylic acid promotes renal endothelial cell injury via HMGB1 acetylation in trichloroethylene-sensitized mice

Abstract

Abstract Viral infection or reactivation seems to be critical in trichloroethylene hypersensitivity syndrome (THS), which is also called occupational medicamentosa-like dermatitis (OMDT) in China. Our previous studies reported that polyinosinic-polycytidylic acid (poly I:C) amplified hepatitis in TCE-sensitized mice. However, whether poly I:C plays a role in TCE-induced renal damage remains to be clarified. To this end, a TCE-sensitized mouse model was established. Renal damage, especially renal endothelial cell dysfunction, was assessed. The activation of high mobility group box protein 1 (HMGB1) was further detected to elucidate the possible role of poly I:C in TCE sensitization-induced renal damage. Our results showed that poly I:C pretreatment aggravated the renal histological changes and dysfunction in TCE-sensitized mice. Renal endothelial cell injuries might be a key driver of kidney damage, in which poly I:C pretreatment acted as an amplifier in TCE sensitization. In addition, poly I:C, combined with Toll-like receptor (TLR) 3, promotes the acetylation and release of HMGB1 from renal endothelial cells. Taken together, our findings highlighted a novel role of poly I:C pretreatment in TCE sensitization-induced renal endothelial cell injuries.