Lh. Wu et al., Induction and regulation of matrix metalloproteinase-12 by cytokines and CD40 signaling in monocyte/macrophages, BIOC BIOP R, 269(3), 2000, pp. 808-815
Citations number
33
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Matrix metalloproteinase-12 (MMP-18) has been shown to play critical roles
in atherogenesis. To determine the cellular mechanisms for control of MMP-1
2 expression, we studied the effects of several cytokines (GM-CSF, IL-1 bet
a, MCP-1) and CD40 ligand on MMP-12 expression in human monocyte/macrophage
s. Undifferentiated U937 monocytic cells and human peripheral blood monocyt
es did not express MMP-12. However, in the presence of GM-CSF, these monocy
tes showed MMP-12 expression at both the transcriptional and protein levels
. The combination of treatment with GM-CSF and IL-1 beta or MCP-1 resulted
in a further increase of MMP-1S expression compared to treatment with GM-CS
F alone. By contrast, both U937-derived macrophages and human peripheral bl
ood monocyte-derived macrophages showed spontaneous MMP-1S expression, whic
h was significantly increased by the addition of either GM-CSF or anti-CD40
Ab. These results indicate that expression of MMP-12 is dependent upon the
state of cellular differentiation and enhanced by cytokines and CD40 signal
ing. (C) 2000 Academic Press.