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.


CONCLUSIONS
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.
Origuchi
T
T
School of Allied Medical Sciences, Nagasaki University, Japan.
Migita
K
K
Nakashima
T
T
Tominaga
M
M
Nakamura
H
H
Nakashima
M
M
Aoyagi
T
T
Kawakami
A
A
Kawabe
Y
Y
Eguchi
K
K
D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000276:immunology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D012333:RNA, Messenger / Q000032:analysis
D007375:Interleukin-1; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2