Stromelysin-1 (MMP3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand

Objective. To investigate the relationship between matrix metalloproteinase s (MMP) and the soluble form of Fas ligand (sFasL) in the synovial fluid (S F) of patients with rheumatoid arthritis (RA), and to determine which MMP h ave a major role in cleaving FasL. Methods. The concentrations of sFas and sFasL in SF from 48 patients with R A and 43 patients with osteoarthritis (OA) were measured using specific ELI SA. The levels of different MMP (MMP-1, 2, 3, 7, 9) in SF were also measure d by ELISA. The active forms of gelatinases were detected by gelatin zymogr am. Human FasL-expressing transfected cells (hFasL/L5178Y) were used to inv estigate whether FasL is cleaved from membrane bound FasL. Results. Significantly higher levels of MMP-1, 3, and 9 were found in SF fr om RA patients compared to OA patients. but MMP-7 was not detectable in eit her group. The concentrations of sFas and sFasL in SF were also higher in R A than in OA patients. However, there was no relationship between the conce ntration of sFas and sFasL. Among MMP, MMP-3 concentrations in SF were clos ely correlated with the level of sFasL and with disease activity of RA. Enz ymatic cleavage assay indicated that MMP-3 has potential to cleave the FasL expressed on hFasL/L5178Y cells and to produce sFasL. Conclusion. There was significant correlation between the concentration of sFasL and MMP-3 in SF of patients with RA. In addition, our data indicate t hat the shedding of FasL may be regulated by MMP-3 in the joint of patients with RA.