PMID- 16105742 OWN - NLM STAT- MEDLINE DCOM- 20051129 LR - 20211203 IS - 1043-4666 (Print) IS - 1043-4666 (Linking) VI - 31 IP - 6 DP - 2005 Sep 21 TI - MCP-1-stimulated chemotaxis of monocytic and endothelial cells is dependent on activation of different signaling cascades. PG - 439-46 AB - Monocyte chemoattractant protein-1 (MCP-1) is important in attracting monocytes to sites of inflammation. Besides induction of monocyte recruitment, MCP-1 can also affect chemotactic response of endothelial cells. The molecular mechanisms involved in MCP-1-induced cell migration are poorly understood. In the current investigation, we demonstrate activation of p42/44(ERK1/2) and p38 mitogen-activated protein kinases (MAPKs), phosphatydilinositol-3-kinase (PI3K) and Src-kinases in both monocytes and endothelial cells stimulated with MCP-1 in vitro. The response was rapid and time-dependent, detectable within 3 min of MCP-1 stimulation. MCP-1-induced phosphorylation of p42/44(ERK1/2) MAPKs was partially blocked by inhibitor of PI3K LY294002, while phosphorylation of p38 MAPK was diminished to a greater extent in presence of Src-kinase inhibitor PP2. There was a substantial inhibition of monocyte migration upon treatment with inhibitors of p38 MAPK, at the same time inhibition of p42/44(ERK1/2) MAPK activation had no effect. On the contrary, the MCP-1-stimulated chemotaxis of endothelial cells was completely abolished by inhibitors of PI3K and p42/44(ERK1/2), but not by p38 MAPK inhibitors. These results suggest that parallel signal transduction pathways are activated by MCP-1, and that depending on the cell type these pathways differentially contribute to cell chemotactic activity. FAU - Arefieva, Tatiana I AU - Arefieva TI AD - Institute of Experimental Cardiology, Cardiology Research Centre, Moscow, Russian Federation. FAU - Kukhtina, Nadezhda B AU - Kukhtina NB FAU - Antonova, Olga A AU - Antonova OA FAU - Krasnikova, Tatiana L AU - Krasnikova TL LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Chemokine CCL2) RN - EC 2.7.11.1 (Protein Serine-Threonine Kinases) RN - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Cells, Cultured MH - Chemokine CCL2/*pharmacology MH - Chemotaxis/*drug effects/physiology MH - Endothelial Cells/*drug effects/physiology MH - Extracellular Signal-Regulated MAP Kinases/drug effects/physiology MH - Fluorescent Antibody Technique MH - Humans MH - Monocytes/*drug effects/physiology MH - Phosphatidylinositol 3-Kinases/drug effects/physiology MH - Protein Serine-Threonine Kinases/drug effects/physiology MH - Signal Transduction/*drug effects MH - p38 Mitogen-Activated Protein Kinases/drug effects/physiology EDAT- 2005/08/18 09:00 MHDA- 2005/12/13 09:00 CRDT- 2005/08/18 09:00 PHST- 2005/01/06 00:00 [received] PHST- 2005/06/21 00:00 [revised] PHST- 2005/06/29 00:00 [accepted] PHST- 2005/08/18 09:00 [pubmed] PHST- 2005/12/13 09:00 [medline] PHST- 2005/08/18 09:00 [entrez] AID - S1043-4666(05)00229-2 [pii] AID - 10.1016/j.cyto.2005.06.016 [doi] PST - ppublish SO - Cytokine. 2005 Sep 21;31(6):439-46. doi: 10.1016/j.cyto.2005.06.016.