Activated á2 macroglobulin induces matrix metalloproteinase 9 expression by low

CACERES LC; BONACCI GR; SÁNCHEZ MC; CHIABRANDO GA

JOURNAL OF CELLULAR BIOCHEMISTRY

WILEY-LISS, DIV JOHN WILEY & SONS INC

Año: 2010 vol. 111 p. 607 - 617

0730-2312

Macrophages under certain stimuli induce matrix metalloproteinase 9 (MMP-9) expression and protein secretion through the activation of MAPK-ERK and NF-êB signaling pathways. Previously, we demonstrated that activated á2-macroglulin (á2M*) 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 á2M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that á2M* 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-êB. Both intracellular signaling pathways activated by á2M* were effectively blocked by calphostin- C, suggesting involvement of PKC. In addition, we demonstrate that á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.êB signaling pathways. Previously, we demonstrated that activated á2-macroglulin (á2M*) 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 á2M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that á2M* 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-êB. Both intracellular signaling pathways activated by á2M* were effectively blocked by calphostin- C, suggesting involvement of PKC. In addition, we demonstrate that á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.á2-macroglulin (á2M*) 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 á2M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that á2M* 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-êB. Both intracellular signaling pathways activated by á2M* were effectively blocked by calphostin- C, suggesting involvement of PKC. In addition, we demonstrate that á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.á2M*/LRP1interaction could induce the MMP-9 production in J774 and Raw264.7 macrophage-derived cell lines. It was shown that á2M* 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-êB. Both intracellular signaling pathways activated by á2M* were effectively blocked by calphostin- C, suggesting involvement of PKC. In addition, we demonstrate that á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.á2M* 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-êB. Both intracellular signaling pathways activated by á2M* were effectively blocked by calphostin- C, suggesting involvement of PKC. In addition, we demonstrate that á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.êB. Both intracellular signaling pathways activated by á2M* were effectively blocked by calphostin- C, suggesting involvement of PKC. In addition, we demonstrate that á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.á2M* were effectively blocked by calphostin- C, suggesting involvement of PKC. In addition, we demonstrate that á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.á2M* produced extracellular calcium influx via LRP1. However, when the intracellular calcium mobilization was inhibited by BAPTA-AM, the á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.á2M*-induced MAPK-ER1/2 activation was fully blocked in both macrophage cell lines. Finally, using specific pharmacological inhibitors for PKC, Mek1 and NF-êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.êB, it was shown that the á2M*-induced MMP-9 protein secretion was inhibited, indicating that the MMP production promoted by the á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.á2M*/LRP1 interaction required the activation of both signaling pathways. These findings may prove useful in the understanding of the macrophage LRP1 role in the vascular wall during atherogenic plaque progression.