Serum amyloid A1 activates the NLRP3 inflammasome via TLR2 to mediate trichloroethylene-induced immune kidney injury.

Renal injury is a key determinant of prognosis of patients afflicted with occupational medicamentosa-like dermatitis due to trichloroethylene (OMDT). Prior investigations have identified damage to renal vascular endothelial cells and elevated serum amyloid A1 (SAA1) levels in individuals with OMDT. Nevertheless, the precise relationship between SAA1 and endothelial cell damage necessitates further elucidation. In the present study, utilizing a trichloroethylene (TCE)-sensitized mouse model alongside cellular experiments, SAA1 inhibitor SGA360 and TLR2 siRNA were employed to explore the specific correlation between SAA1 and endothelial cell damage. The findings demonstrated that TCE-sensitized mice exhibited pronounced renal injury and damage to renal vascular endothelial cells, which were associated with the activation of the NLRP3 inflammasome. Pretreatment with SGA360 effectively inhibited NLRP3 inflammasome activation and mitigated renal injury. Further investigations revealed that SAA1 interacts with TLR2, rather than TLR4, to activate the NLRP3 inflammasome. In vitro experiments, wherein human umbilical vein endothelial cells (HUVECs) were exposed to 1.25 μg/mL of SAA1 and TLR2 small interfering RNA (siRNA), demonstrated that SAA1 activates the NLRP3 inflammasome through its interaction with TLR2. This activation promotes GSDMD-mediated pyroptosis, thereby compromising the endothelial barrier. The study concluded that SAA1 interacts with TLR2 receptors located on the surface of renal vascular endothelial cells, leading to the activation of the NLRP3 inflammasome. This activation initiates pyroptosis and the substantial release of inflammatory cytokines, which undermine the integrity of the renal vascular endothelial barrier. Consequently, this disruption impairs glomerular filtration and tubular reabsorption functions.