Premium
Differential Signaling for MCP‐1‐Dependent Integrin Activation and Chemotaxis
Author(s) -
ASHIDA NOBORU,
ARAI HIDENORI,
YAMASAKI MASAHIDE,
KITA TORU
Publication year - 2001
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2001.tb03969.x
Subject(s) - chemotaxis , integrin , microbiology and biotechnology , mapk/erk pathway , monocyte , p38 mitogen activated protein kinases , chemistry , cell adhesion , signal transduction , cell , biology , immunology , receptor , biochemistry
A bstract : Transmigration of monocytes to the subendothelial space is the initial step in atherosclerotic plaque formation and inflammation. Integrin activation and chemotaxis are two important functions in monocyte transmigration. To delineate the signaling cascades leading to integrin activation and chemotaxis by monocyte chemoattractant protein‐1 (MCP‐1), we investigated the roles of MAPK in THP‐1 cells, a monocytic cell line. MCP‐1 stimulated β1 integrin‐dependent, but not β2 integrin‐dependent cell adhesion in a time‐dependent manner. MCP‐1‐mediated cell adhesion was inhibited by a MEK inhibitor, but not by a p38‐MAPK inhibitor. By contrast, MCP‐1‐mediated chemotaxis was inhibited by the p38‐MAPK inhibitor, but not by the MEK inhibitor. These data indicate that ERK is responsible for integrin activation and that p38‐MAPK is responsible for chemotaxis mediated by MCP‐1. This study demonstrates that two distinct MAPKs regulate two dependent signaling cascades, leading to integrin activation and chemotaxis induced by MCP‐1 in THP‐1 cells.