IL-1-mediated expression of membrane type matrix-metalloproteinase in rheumatoid osteoblasts.

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.