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

Objective To determine whether the activation of metalloproteinases can be achieved b y the interaction of the inflammatory cytokine, IL-IP, with rheumatoid oste oblasts. Results MMP-2 is not secreted by rheumatoid osteoblasts as a proenzyme; however; IL -IP stimulation induced the secretion of MMP-2 as an active form from rheum atoid osteoblasts. This MMP-2 activating activity was detected significantl y in IL-IP-stimulated rheumatoid osteoblasts. In support of this result, IL -I beta stimulation induced the expression of membrane type matrix-metallop roteinase (MT-MMP) a newly-identified MMP-2 specific activator in rheumatoi d osteoblasts. Conclusion These results suggest that IL-IP induces MMP-2 activation in part by up-reg ulating MT-MMP expression and represents a new mechanism for. cytokine-medi ated articular destruction in RA.