LPS-Induced Inflammatory Microenvironment Aggravates Urothelial Cell Damage and MAP Crystal Adhesion

Magnesium ammonium phosphate (MAP) stones feature a markedly high recurrence rate. The inflammatory microenvironment contributes to MAP crystal-induced urothelial injury, yet the specific regulatory mechanisms remain unclear. In this study, MAP crystals were synthesized, and pharmacological intervention with the ROS scavenger N-acetylcysteine (NAC), the CTSB inhibitor CA-074 Me, and the NLRP3 inhibitor MCC950 was used to explore the signaling pathway through which MAP crystals induce inflammatory responses; an inflammatory model of SV-HUC-1 urothelial cells was established using lipopolysaccharides (LPSs) to observe the regulation of key molecules in the inflammatory signaling pathway and its effects on MAP crystal adhesion and cellular injury. Results showed that MAP crystals elevated intracellular ROS levels, aggravated lysosomal membrane permeabilization, triggered CTSB leakage, and activated the NLRP3 inflammasome pathway. In the LPS-induced inflammatory microenvironment, MAP crystals exacerbated cellular inflammatory responses and cell injury. Meanwhile, the expression of adhesion-related proteins, including OPN, CD44, and ICAM-1, was further upregulated, accompanied by aggravated MAP crystal adhesion. In summary, MAP crystals induced inflammation in SV-HUC-1 cells via the ROS–CTSB–NLRP3 axis, and the LPS-induced inflammatory microenvironment further amplified cellular inflammation, cell damage, and crystal adhesion. This study provides theoretical evidence supporting the pro-inflammatory effect of the inflammatory microenvironment on MAP stone formation.