Stromelysin-1 (MMP-3) in synovial fluid of patients with rheumatoid arthritis has potential to cleave membrane bound Fas ligand.
OBJECTIVE
To investigate the relationship between matrix metalloproteinases (MMP) and the soluble form of Fas ligand (sFasL) in the synovial fluid (SF) of patients with rheumatoid arthritis (RA), and to determine which MMP have a major role in cleaving FasL.


METHODS
The concentrations of sFas and sFasL in SF from 48 patients with RA and 43 patients with osteoarthritis (OA) were measured using specific ELISA. The levels of different MMP (MMP-1, 2, 3, 7, 9) in SF were also measured by ELISA. The active forms of gelatinases were detected by gelatin zymogram. Human FasL-expressing transfected cells (hFasL/L5178Y) were used to investigate whether FasL is cleaved from membrane bound FasL.


RESULTS
Significantly higher levels of MMP-1, 3, and 9 were found in SF from RA patients compared to OA patients, but MMP-7 was not detectable in either group. The concentrations of sFas and sFasL in SF were also higher in RA than in OA patients. However, there was no relationship between the concentration of sFas and sFasL. Among MMP, MMP-3 concentrations in SF were closely correlated with the level of sFasL and with disease activity of RA. Enzymatic cleavage assay indicated that MMP-3 has potential to cleave the FasL expressed on hFasL/L5178Y cells and to produce sFasL.


CONCLUSIONS
There was significant correlation between the concentration of sFasL and MMP-3 in SF of patients with RA. In addition, our data indicate that the shedding of FasL may be regulated by MMP-3 in the joint of patients with RA.
Matsuno
H
H
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan. matsuno@ms.toyama-mpu.ac.jp
Yudoh
K
K
Watanabe
Y
Y
Nakazawa
F
F
Aono
H
H
Kimura
T
T
D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000201:enzymology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D053222:Fas Ligand Protein; D005260:Female; D006801:Humans; D019272:Leukocyte Elastase / Q000378:metabolism; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D013582:Synovial Fluid / Q000201:enzymology*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019272:Leukocyte Elastase; D019278:Matrix Metalloproteinase 3