MCP-1 induces activation of MAP-kinases ERK, JNK and p38 MAPK in human endothelial cells

• Published in: Cardiovascular research Vol. 56; no. 2; pp. 284 - 292
• Main Authors: WERLE, Martina, SCHMAL, Ulrike, HANNA, Katharina, KREUZER, Jörg
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.11.2002
• Subjects: Biological and medical sciences; Blood vessels and receptors; Cell Culture Techniques; Chemokine CCL2 - pharmacology; Endothelium, Vascular - drug effects; Endothelium, Vascular - enzymology; Fundamental and applied biological sciences. Psychology; Gene Expression; Humans; JNK Mitogen-Activated Protein Kinases; Mitogen-Activated Protein Kinases - metabolism; p38 Mitogen-Activated Protein Kinases; Phosphorylation; Receptors, CCR2; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; RNA, Messenger - genetics; Signal Transduction; Vertebrates: cardiovascular system; Human origin; Endothelial cell; Atherosclerosis;: Endothelial function; Extracellular signal-regulated protein kinase; Enzyme; Exploration; Signal transduciton; Signal transduction; Regulation(control); Enzymatic activity; Blood vessel; Circulatory system; Vascular wall; Monocyte chemoattractant protein 1
• ISSN: 0008-6363; 1755-3245
• DOI: 10.1016/s0008-6363(02)00600-4

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.