c-Jun N-terminal kinases inhibitor suppresses the TNF-α induced MCP-1 expression in human umbilical vein endothelial cells

被引:13
作者
Ahmed, Rania Abdel Muneem [1 ]
Murao, Koji [1 ]
Imachi, Hitomi [1 ]
Yoshida, Kazuya [1 ]
Dobashi, Hiroaki [1 ]
Hosomi, Naohisa [2 ]
Ishida, Toshihiko [1 ]
机构
[1] Kagawa Univ, Div Endocrinol & Metab, Dept Internal Med, Fac Med, Miki, Kagawa 7610793, Japan
[2] Kagawa Univ, Dept Cardiorenal & Cerebrovasc Med, Fac Med, Miki, Kagawa 7610793, Japan
关键词
JNKI-1; MCP-1; TNF-alpha; JNK; HUVEC; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SIGNAL-TRANSDUCTION PATHWAY; KAPPA B ACTIVATION; RECEPTOR CLASS BI; GENE-EXPRESSION; JNK; CHEMOKINES; ATHEROSCLEROSIS; STIMULATION; PEPTIDE;
D O I
10.1007/s12020-008-9136-0
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:184 / 188
页数:5
相关论文
共 24 条
[1]   Thyrotropin-releasing hormone-stimulated thyrotropin expression involves islet-brain-1/c-Jun N-terminal kinase interacting protein-1 [J].
Abe, H ;
Murao, K ;
Imachi, H ;
Cao, WM ;
Yu, X ;
Yoshida, K ;
Wong, NCW ;
Shupnik, MA ;
Haefliger, JA ;
Waeber, G ;
Ishida, T .
ENDOCRINOLOGY, 2004, 145 (12) :5623-5628
[2]   Signalling pathways of the TNF superfamily: A double-edged sword [J].
Aggarwal, BB .
NATURE REVIEWS IMMUNOLOGY, 2003, 3 (09) :745-756
[3]   INTERLEUKIN-1 ACTS ON CULTURED HUMAN VASCULAR ENDOTHELIUM TO INCREASE THE ADHESION OF POLYMORPHONUCLEAR LEUKOCYTES, MONOCYTES, AND RELATED LEUKOCYTE CELL-LINES [J].
BEVILACQUA, MP ;
POBER, JS ;
WHEELER, ME ;
COTRAN, RS ;
GIMBRONE, MA .
JOURNAL OF CLINICAL INVESTIGATION, 1985, 76 (05) :2003-2011
[4]   Cell-permeable peptide inhibitors of JNK novel blockers of β-cell death [J].
Bonny, C ;
Oberson, A ;
Negri, S ;
Sauser, C ;
Schorderet, DF .
DIABETES, 2001, 50 (01) :77-82
[5]   Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis [J].
Boring, L ;
Gosling, J ;
Cleary, M ;
Charo, IF .
NATURE, 1998, 394 (6696) :894-897
[6]   A cytoplasmic inhibitor of the JNK signal transduction pathway [J].
Dickens, M ;
Rogers, JS ;
Cavanagh, J ;
Raitano, A ;
Xia, ZG ;
Halpern, JR ;
Greenberg, ME ;
Sawyers, CL ;
Davis, RJ .
SCIENCE, 1997, 277 (5326) :693-696
[7]   Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases [J].
Johnson, GL ;
Lapadat, R .
SCIENCE, 2002, 298 (5600) :1911-1912
[8]   Possible novel therapy for diabetes with cell-permeable JNK-inhibitory peptide [J].
Kaneto, H ;
Nakatani, Y ;
Miyatsuka, T ;
Kawamori, D ;
Matsuoka, T ;
Matsuhisa, M ;
Kajimoto, Y ;
Ichijo, H ;
Yamasaki, Y ;
Hori, M .
NATURE MEDICINE, 2004, 10 (10) :1128-1132
[9]   TRAF2 is essential for JNK but not NF-kappa B activation and regulates lymphocyte proliferation and survival [J].
Lee, SY ;
Reichlin, A ;
Santana, A ;
Sokol, KA ;
Nussenzweig, MC ;
Choi, Y .
IMMUNITY, 1997, 7 (05) :703-713
[10]   HUMAN MONOCYTE CHEMOATTRACTANT PROTEIN-1 (MCP-1) [J].
LEONARD, EJ ;
YOSHIMURA, T .
IMMUNOLOGY TODAY, 1990, 11 (03) :97-101