Target complement factor H / serum amyloid a signaling in trichloroethylene-induced immune kidney injury

The aberrant activation of the intracellular complement system is a significant characteristic of trichloroethylene (TCE) -induced immune kidney injury. However, the specific role of complement factor H (CFH) in this context remains unclear. This study investigates the involvement of CFH / serum amyloid A (SAA1) signaling in TCE-induced immune kidney injury by employing a combination of in vitro experiments and TCE-sensitized mouse model. Proteomic analyses results revealed that TCE-sensitized positive mice exhibited significantly increased expression of acute-phase reactive proteins, abnormal activation of the complement system. The treatment with TNFα and IFNγ-neutralizing antibodies reduced renal vascular endothelial cell injury and kidney damage in TCE-sensitized mice, and the combined treatment of recombinant TNFα and IFNγ reduced CFH intracellular expression but increased extracellular secretion in human renal glomerular endothelial cells (HRGECs). CFH in HRGECs notably protected endothelial barrier function when stimulated by TNFα and IFNγ. Moreover, CFH deficiency can lead to increased SAA1, which interacts with Toll-like receptor-2 (TLR2) to activate nuclear factor-kappaB (NF-κB). This study revealed that the combination of TNFα and IFNγ influences renal vascular endothelial barrier function by regulating the expression and secretion of local CFH. The downregulated intracellular CFH also associated with the inflammatory response in TCE-induced immune kidney injury by regulating the SAA1/TLR2 pathway.