Th2 Cell Membrane Factors in Association with IL-4 Enhance Matrix Metalloproteinase-1(MMP-1)While Decreasing MMP-9 Production by Granulocyte-Macrophage MMP-9 Production by Granulocyte-Macrophage Colony-Stimulating Factor-Differentiated Human Monocyt

摘要

Monocytes/macrophages are directly involved in tissue remodeling and tissure destruction through the release of matrix metallo-proteinases(MMP).In the present study,we examined the effect mediated by contact of polarized The cells with mononuclear phagocytes on the production of MMP-1,MMP-9,and their inhibitor.Plasma cell membranes from Ag-activated Th1 and Th2 cells were potent inducers of MMP-1 production by THP-1 cells.Cell membrane-associated TNF was found to be only partially involved in MMP-1 induction by toth Th1 and Th2 cells.In Th2 cells exclusively,membrane-associated IL-4 induced MMP-1 production by THP-1 cells.This membrane-associated IL-4 effect was additive to that of TNF and was specifically observed on MMP-1 as MMP-9 production was concomitantly inhibited.Similarly,soluble IL-4 induced THP-1 cells to produce MMP-1,its effect proving additive to that of soluble TNF and to that of cell membranes of mitogen-activated HUT-78 cells.Its activity was blocked by IL-4 neutralization,and was unaffected by the presence of indomethacin.These effects on THP-1 cells were observed at protein and mRNA levels.Although inhibitory on freshly isolated peripheral blood monocytes,soluble IL_4 enhanced T cell-induced MMP-1 and inhibited MMP-9 production both at protein and mRNA levels in monocytes cultured for 7 days in the presence of GM-CSF.Thus,in contrast with previously reported effects,Th2 and IL-4 specifically induce MMP-1 production by mononuclear phagocytes at various stages of differentiation.This IL-4 activity may be relevant to pathological conditions dominated by Th2 inflammatory responses,resulting in tissue remodeling and destruction.