Regulation of early cartilage destruction in inflammatory arthritis by death receptor 3.

摘要: Objective To investigate the role of death receptor 3 (DR-3) and its ligand tumor necrosis factor–like molecule 1A (TL1A) in early stages inflammatory arthritis. Methods Antigen-induced arthritis (AIA) was generated C57BL/6 mice deficient DR-3 gene (DR3−/−) their DR3+/+ (wild-type) littermates by priming intraarticular injection methylated bovine serum albumin. The joints were sectioned analyzed histochemically for damage to cartilage expression DR3, TL1A, Ly-6G (a marker neutrophils), gelatinase matrix metalloproteinase 9 (MMP-9), aggrecanase ADAMTS-5, neutrophil chemoattractant CXCL1. In vitro production MMP-9 measured cultures from fibroblasts, macrophages, neutrophils following addition TL1A other proinflammatory stimuli. Results DR3 up-regulated wild-type generation AIA. DR3−/− protected against compared with mice, even at time points prior main accumulation Teff cells joint. Early protection AIA vivo correlated reduced levels MMP-9. vitro, major producers MMP-9, while numbers mice. However, neither induced release nor affected survival neutrophils. Instead, CXCL1 observed mice. Conclusion DR-3 drives destruction model through CXCL1, maximizing recruitment joint leading enhanced local cartilage-destroying enzymes.