Induction and regulation of matrix metalloproteinase-12 by cytokines and CD40 signaling in monocyte/macrophages.
Matrix metalloproteinase-12 (MMP-12) has been shown to play critical roles in atherogenesis. To determine the cellular mechanisms for control of MMP-12 expression, we studied the effects of several cytokines (GM-CSF, IL-1beta, MCP-1) and CD40 ligand on MMP-12 expression in human monocyte/macrophages. Undifferentiated U937 monocytic cells and human peripheral blood monocytes did not express MMP-12. However, in the presence of GM-CSF, these monocytes showed MMP-12 expression at both the transcriptional and protein levels. The combination of treatment with GM-CSF and IL-1beta or MCP-1 resulted in a further increase of MMP-12 expression compared to treatment with GM-CSF alone. By contrast, both U937-derived macrophages and human peripheral blood monocyte-derived macrophages showed spontaneous MMP-12 expression, which was significantly increased by the addition of either GM-CSF or anti-CD40Ab. These results indicate that expression of MMP-12 is dependent upon the state of cellular differentiation and enhanced by cytokines and CD40 signaling.
Wu
L
L
Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.
Fan
J
J
Matsumoto
S i
Si
Watanabe
T
T
D019013:CD40 Antigens / Q000502:physiology*; D023201:CD40 Ligand; D018932:Chemokine CCL2 / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology*; D004790:Enzyme Induction; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D008264:Macrophages / Q000201:enzymology* / Q000276:immunology; D053508:Matrix Metalloproteinase 12; D008562:Membrane Glycoproteins / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics*; D009000:Monocytes / Q000201:enzymology* / Q000276:immunology; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D020298:U937 Cells
D019013:CD40 Antigens; D018932:Chemokine CCL2; D016207:Cytokines; D007375:Interleukin-1; D008562:Membrane Glycoproteins; D023201:CD40 Ligand; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D008666:Metalloendopeptidases; C507122:MMP12 protein, human; D053508:Matrix Metalloproteinase 12; D013755:Tetradecanoylphorbol Acetate