VE-cadherin may suppress inflammation depending on the phase of inflammation of rheumatoid arthritis

Objectives A disintegrin and metalloproteinase (ADAM)-15 and vascular endothelial (VE)-cadherin are involved in angiogenesis. We investigated the relationship between ADAM-15 and VE-cadherin expressions in rheumatoid arthritis (RA). Methods VE-cadherin concentrations in the serum of patients with RA were measured using the enzyme linked immunosorbent assay (ELISA). We stimulated fibroblast-like synoviocytes (RA-FLS) with VE-cadherin and measured the vascular endothelial growth factor (VEGF) and inflammatory cytokine levels using ELISA. We also examined the correlation between serum VE-cadherin levels and DAS-28ESR and used the Matrigel assay to examine VE-cadherin involvement in angiogenesis. Results Serum VE-cadherin levels were significantly higher in patients with RA than in healthy controls. A negative correlation was observed between VE-cadherin and DAS-28ESR. VEGF, chemokine ligand 16, intercellular adhesion molecule-1, and interleukin-8 levels in the supernatant of RA-FLS or human umbilical vein endothelial cells stimulated with VE-cadherin were significantly lower than those in the controls. The number of intercellular bridges formed by endothelial cells using Matrigel significantly decreased in RA synovial fluids from which VE-cadherin had been removed compared to synovial fluids treated with control immunoglobulin G. Conclusion VE-cadherin may have an inhibitory effect on inflammation depending on the phase of RA inflammation.