Activated alpha(2) macroglobulin induces matrix metalloproteinase 9 expression by low-density lipoprotein receptor-related protein 1 through MAPK-ERK1/2 and NF-kappaB activation in macrophage-derived cell lines

CÁCERES LC, BONACCI GR, SÁNCHEZ MC, CHIABRANDO GA.

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2010 vol. 111 p. 607 - 607

acrophages under certain stimuli induce matrix metalloproteinase 9 (MMP-9) expression and protein secretion through the activation of MAPK-ERK and NF-kappaB signaling pathways. Previously, we demonstrated that activated alpha(2)-macroglulin (alpha(2)M*) through the interaction with its receptor low-density lipoprotein receptor-related protein 1 (LRP1) induces macrophage proliferation mediated by the activation of MAPK-ERK1/2. In the present work, we examined whether alpha(2)M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that alpha(2)M* promoted MMP-9 expression and protein secretion by LRP1 in both macrophage-derived cell lines, which was mediated by the activation of MAPK-ERK1/2 and NF-kappaB. Both intracellular signaling pathways activated by alpha(2)M* were effectively blocked by calphostin-C, suggesting involvement of PKC. In addition, we demonstrate that alpha(2)M* produced extracellular calcium influx via LRP