Dynamics of matrix metalloproteinase-9 (MMP-9) in patients with rheumatoid arthritis, with special reference to tissue inhibitor of metalloproteinase-1 (TIMP-1).:special reference to tissue inhibitor of metalloproteinase-1 (TIMP-1)

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In order to investigate the dynamics of metalloproteinase-9 (MMP-9), we measured proMMP-9 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in sera and joint fluids by sandwich enzyme linked immunosorbent assay (ELISA), and examined immunohistochemically the expression of the proteins in joint tissues from patients with rheumatoid arthritis (RA) . ProMMP-9 concentration in 86 sera (749.4+940.2 ng/ml) and 54 joints fluids (4539.9±7681.5 ng/ml) from patients with RA was significantly higher than those of patients with osteoarthritis (OA) and controls. Immunohistochemistry showed that in rheumatoid synovium proMMP-9 localized in neutrophils and monocytes diffusely infiltrated the sublining layer. In addition, osteoclasts in rheumatoid subchondral bone were intensively stained. Both the concentration of proMMP-9 and the molar ratio of proMMP-9/TIMP-1 positively correlated to the number proMMP-9 positive cells in RA synovia (r=0.607, r=0.507) and the score of Roony's diffuse infiltrated of lymphocytes (r=0.720, r=0.591), respectively, although they were not correlated to the stage and class of Steinbrocker's and to the clinical laboratorial data. Our results suggest MMP-9 produced by neutrophils and monocytes plays a role in tissue destruction of RA joint, and may be regulated by lymphocytes.
日本炎症・再生医学会の論文