title: c-Jun N-terminal kinases inhibitor suppresses the TNF-alpha induced MCP-1 expression in human umbilical vein endothelial cells.
abstract: 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.
authors.affiliation: 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.
authors.forename: Rania Abdel Muneem
authors.initials: RA
authors.lastname: Ahmed
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
authors.forename: Hitomi
authors.initials: H
authors.lastname: Imachi
authors.forename: Kazuya
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Dobashi
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Ishida
mesh_terms: 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*
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D048031:JNK Mitogen-Activated Protein Kinases