PMID- 12393099 OWN - NLM STAT- MEDLINE DCOM- 20021216 LR - 20190513 IS - 0008-6363 (Print) IS - 0008-6363 (Linking) VI - 56 IP - 2 DP - 2002 Nov TI - MCP-1 induces activation of MAP-kinases ERK, JNK and p38 MAPK in human endothelial cells. PG - 284-92 AB - Activation of vascular endothelial cells (ECs) plays an important pathogenic role in the development of atherosclerosis. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemoattractant of monocytes. Besides induction of monocyte recruitment, it has been suggested that MCP-1 can also affect the cellular responses of ECs. We investigated whether MCP-1 activated the three major mitogen activated protein (MAP)-kinases extracellular signal-regulated kinase (ERK), c-Jun amino terminal kinase (JNK) and p38 MAPK. Stimulation of ECs with MCP-1 induced a time- and concentration-dependent activation of all three MAP-kinases, concentrations as low as 0.1 ng/ml were sufficient for this mechanism. MCP-1 also induced secretion of matrix metalloproteinase (MMP)-2 which along with ERK activation was inhibited by PD098059. The results demonstrate that MCP-1 can lead to direct activation of MAP kinases together with induction of MMP2 in ECs. Our data thus propose a new mechanism for the proatherogenic effect of MCP-1. FAU - Werle, Martina AU - Werle M AD - Innere Medizin III, Universitat Heidelberg, Bergheimer Strasse, 58 69115, Heidelberg, Germany. FAU - Schmal, Ulrike AU - Schmal U FAU - Hanna, Katharina AU - Hanna K FAU - Kreuzer, Jorg AU - Kreuzer J LA - eng PT - Journal Article PL - England TA - Cardiovasc Res JT - Cardiovascular research JID - 0077427 RN - 0 (CCR2 protein, human) RN - 0 (Chemokine CCL2) RN - 0 (RNA, Messenger) RN - 0 (Receptors, CCR2) RN - 0 (Receptors, Chemokine) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases) SB - IM MH - Cell Culture Techniques MH - Chemokine CCL2/*pharmacology MH - Endothelium, Vascular/*drug effects/*enzymology MH - Gene Expression MH - Humans MH - JNK Mitogen-Activated Protein Kinases MH - Mitogen-Activated Protein Kinases/*metabolism MH - Phosphorylation MH - RNA, Messenger/genetics MH - Receptors, CCR2 MH - Receptors, Chemokine/genetics/metabolism MH - Signal Transduction MH - p38 Mitogen-Activated Protein Kinases EDAT- 2002/10/24 04:00 MHDA- 2002/12/18 04:00 CRDT- 2002/10/24 04:00 PHST- 2002/10/24 04:00 [pubmed] PHST- 2002/12/18 04:00 [medline] PHST- 2002/10/24 04:00 [entrez] AID - S0008636302006004 [pii] AID - 10.1016/s0008-6363(02)00600-4 [doi] PST - ppublish SO - Cardiovasc Res. 2002 Nov;56(2):284-92. doi: 10.1016/s0008-6363(02)00600-4.