PMID- 11795297 OWN - NLM STAT- MEDLINE DCOM- 20020201 LR - 20190616 IS - 0077-8923 (Print) IS - 0077-8923 (Linking) VI - 947 DP - 2001 Dec TI - Differential signaling for MCP-1-dependent integrin activation and chemotaxis. PG - 387-9 AB - 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 beta1 integrin-dependent, but not beta2 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. FAU - Ashida, N AU - Ashida N AD - Department of Geriatric Medicine, Kyoto University Graduate School of Medicine, Japan. ash@kuhp.kyoto.u.ac.jp FAU - Arai, H AU - Arai H FAU - Yamasaki, M AU - Yamasaki M FAU - Kita, T AU - Kita T LA - eng PT - Journal Article PL - United States TA - Ann N Y Acad Sci JT - Annals of the New York Academy of Sciences JID - 7506858 RN - 0 (Chemokine CCL2) RN - 0 (Enzyme Inhibitors) RN - 0 (Fibronectins) RN - 0 (Flavonoids) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) RN - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one) SB - IM MH - Cell Line MH - Chemokine CCL2/*pharmacology MH - *Chemotaxis, Leukocyte/drug effects/*physiology MH - Enzyme Inhibitors/pharmacology MH - Fibronectins/metabolism MH - Flavonoids/pharmacology MH - Humans MH - Mitogen-Activated Protein Kinases/antagonists & inhibitors MH - Monocytes/drug effects/physiology MH - Signal Transduction/*physiology MH - p38 Mitogen-Activated Protein Kinases EDAT- 2002/01/25 10:00 MHDA- 2002/02/02 10:01 CRDT- 2002/01/25 10:00 PHST- 2002/01/25 10:00 [pubmed] PHST- 2002/02/02 10:01 [medline] PHST- 2002/01/25 10:00 [entrez] AID - 10.1111/j.1749-6632.2001.tb03969.x [doi] PST - ppublish SO - Ann N Y Acad Sci. 2001 Dec;947:387-9. doi: 10.1111/j.1749-6632.2001.tb03969.x.