Lipopolysaccharide (LPS) blocks the activated alpha 2-Macroglobulin-induced MAPK-ERK1/2 phosphorylation mediated by LRP-1 in the J774 macrophage-derived cell line

BONACCI GR; CACERES L; SANCHEZ MC; CHIABRANDO GA

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS

ELSEVIER SCIENCE INC

Año: 2007 vol. 460 p. 100 - 106

0003-9861

The low-density lipoprotein receptor-related protein-1 (LRP-1) is an endocytic receptor of activated forms of the proteinase inhibitor 2-macroglobulin (2M¤). It has been proposed that 2M¤ and LRP-1 modulate diverse cellular processes, including cell adhesion, proliferation, and migration, which are involved in inXammation and tumor progression. However, relatively little is known about the role of and migration, which are involved in inXammation and tumor progression. However, relatively little is known about the role of 2-macroglobulin (2M¤). It has been proposed that 2M¤ and LRP-1 modulate diverse cellular processes, including cell adhesion, proliferation, and migration, which are involved in inXammation and tumor progression. However, relatively little is known about the role ofXammation and tumor progression. However, relatively little is known about the role of 2M¤/LRP-1 interaction on these processes. In this work, we demonstrate that 2M¤ binding to LRP-1 induces cell proliferation and MAPK activation in the J774 macrophage-derived cell line, which were blocked by RAP, an antagonist of LRP-1-binding ligands, and by PD980059, a speciWc inhibitor for the Mek1-ERK1/2 pathway. In addition, we demonstrate that LPS, a bacterial product that it is known to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. MAPK activation in the J774 macrophage-derived cell line, which were blocked by RAP, an antagonist of LRP-1-binding ligands, and by PD980059, a speciWc inhibitor for the Mek1-ERK1/2 pathway. In addition, we demonstrate that LPS, a bacterial product that it is known to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. 2M¤/LRP-1 interaction on these processes. In this work, we demonstrate that 2M¤ binding to LRP-1 induces cell proliferation and MAPK activation in the J774 macrophage-derived cell line, which were blocked by RAP, an antagonist of LRP-1-binding ligands, and by PD980059, a speciWc inhibitor for the Mek1-ERK1/2 pathway. In addition, we demonstrate that LPS, a bacterial product that it is known to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. Wc inhibitor for the Mek1-ERK1/2 pathway. In addition, we demonstrate that LPS, a bacterial product that it is known to down-regulate the LRP-1 expression on macrophage, abrogated the signaling activity triggered by 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. 2M¤ on LPS-treated J774 cells. These results suggest that 2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer.2M¤/LRP-1 interaction constitutes a key role in the macrophage functioning during inXammation and cancer. © 2007 Elsevier Inc. All rights reserved.2007 Elsevier Inc. All rights reserved.