c-Jun N-terminal kinases inhibitor suppresses the TNF-alpha induced MCP-1 expression in human umbilical vein endothelial cells.
Monocyte chemoattractant protein-1 (MCP-1) is a 76-amino-acid chemokine that is considered to be an important chemotactic factor for monocytes. MCP-1 is expressed in the macrophage-rich areas of atherosclerotic lesions. A recent report indicated that MCP-1 expression in human umbilical vein endothelial cells (HUVECs) is induced by the stimulation of tumor necrosis factor (TNF)-alpha via the c-Jun N-terminal kinases (JNK) pathway. In this study, we examined the effects of JNK inhibitor (JNKI-1), on MCP-1 expression. The results of this study indicated that the expression of MCP-1 mRNA and protein were stimulated in the presence of TNF-alpha. TNF-alpha stimulated the phosphrylation of JNK, however, JNKI-1 inhibited the TNF-alpha stimulated MCP-1 secretion and gene expression. As expected, JNKI-1 blocked the stimulatory effect of TNF-alpha on the MCP-1 promoter activity. In conclusion, JNKI-1 partially inhibits the TNF-alpha-induced MCP-1 expression in HUVECs, and therefore JNKI-1 may be of therapeutic value in the treatment of diseases such as atherosclerosis.
Ahmed
Rania Abdel Muneem
RA
Division of Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Murao
Koji
K
Imachi
Hitomi
H
Yoshida
Kazuya
K
Dobashi
Hiroaki
H
Hosomi
Naohisa
N
Ishida
Toshihiko
T
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics*; D042783:Endothelial Cells / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D014471:Umbilical Veins / Q000737:chemistry*
C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases