Biochem Biophys Res Commun. 2000 Mar 24;269(3):808-15.

Induction and regulation of matrix metalloproteinase-12 by cytokines and CD40 signaling in monocyte/macrophages.

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Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8575, Japan.

Abstract

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.

PMID:: 10720497; [PubMed - indexed for MEDLINE]

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