Association of TNF-α upregulation of MMP-9 activation in monocyte-derived macrophages with progression of joint damage in patients with rheumatoid arthritis |
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| Authors: | XIE Jian-min WANG Hao-wen LU Cai-sheng |
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| Institution: | 1.Department of Rheumatology, Hainan Province Peoples Hospital, Haikou 570311, China;2.The University of Pittsburgh School of Medicine, Pittsburgh PA 15260, America. E-mail:xiejmdoc@163.com |
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| Abstract: | AIM: To explore the expression and activation of matrix metalloproteinase-9 (MMP-9) from monocyte-derived macrophages induced by tumor necrosis factor-α (TNF-α) and to investigate its association with progression of joint damage in patients with rheumatoid arthritis. METHODS: TNF-α and MMP-9 in serum and synovial fluid from patients with early RA and controls were tested with a double-antibody enzyme-linked immunosorbent assay. The correlation between MMP-9 and Larsen score over the first 12 months was analyzed. THP-1 cells differentiated by the treatment with TPA were stimulated with increasing concentration of TNF-α for 24 h in vitro. The protein expression of MMP-9 was determined by Western blotting. The activity of MMP-9 was measured by gelatinolytic zymography. Boyden chamber-matrigel in vitro invasion assay was used to detect the invasive capacity. RESULTS: The levels of TNF-α and MMP-9 in serum and synovial fluid of RA patients were significantly higher than those in controls (P<0.05). Serum and synovial fluid levels of MMP-9 correlated significantly with Larsen score (r=0.37 and 0.32, P<0.01). The MMP-9 activity and invasive ability of co-cultured THP-1 cells with TNF-α and TPA were higher than those of non-TNF-α treatment. CONCLUSION: TNF-α upregulates MMP-9 activation and promotes infiltration of monocyte-derived macrophages, indicating that TNF-α play an important role in the pathogenesis of RA. |
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