Th2 cell membrane factors in association with IL-4 enhance matrix metalloproteinase-1 (MMP-1) while decreasing MMP-9 production by granulocyte-macrophage colony-stimulating factor-differentiated human monocytes

Monocytes/macrophages are directly involved in tissue remodeling and tissue destruction through the release of matrix metalloproteinases (MMP), In the present study, we examined the effect mediated by contact of polarized Th cells with mononuclear phagocytes on the production of MMP-1, MMP-9, and th eir inhibitor. Plasma cell membranes from Ag-activated Th1 and Th2 cells we re potent inducers of MMP-1 production by THP-1 cells. Cell membrane-associ ated TNF; was found to be only partially involved in MMP-1 induction by bot h Th1 and Th2 cells, In Th2 cells exclusively, membrane-associated IL-4 ind uced MMP-1 production by THP-I 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 TH P-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 ac tivity was blocked by IL-4 neutralization, and was unaffected by the presen ce of indomethacin, These effects on THP-1 cells were observed at protein a nd mRNA levels. Although inhibitory on freshly isolated peripheral blood mo nocytes, soluble IL-4 enhanced T cell-induced MMP-1 and inhibited MMP-9 pro duction 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 phagocyt es at various stages of differentiation. This IL-4 activity may be relevant to pathological conditions dominated by Th2 inflammatory responses, result ing in tissue remodeling and destruction.