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IL-1-mediated expression of membrane type matrix-metalloproteinase in rheumatoid osteoblasts
T Origuchi1, K Migita, T Nakashima
1School of Allied Medical Sciences, Nagasaki University, Japan.
Objective:
To determine whether the activation of metalloproteinases can be achieved by the interaction of the inflammatory cytokine, IL-1 beta, with rheumatoid osteoblasts.
Results:
MMP-2 is not secreted by rheumatoid osteoblasts as a proenzyme; however, IL-1 beta stimulation induced the secretion of MMP-2 as an active form from rheumatoid osteoblasts. This MMP-2 activating activity was detected significantly in IL-1 beta-stimulated rheumatoid osteoblasts. In support of this result, IL-1 beta stimulation induced the expression of membrane type matrix-metalloproteinase (MT-MMP), a newly-identified MMP-2 specific activator, in rheumatoid osteoblasts.
Conclusion:
These results suggest that IL-1 beta induces MMP-2 activation in part by up-regulating MT-MMP expression and represents a new mechanism for cytokine-mediated articular destruction in RA.
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