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Erschienen in: Inflammation Research 1/2012

01.01.2012 | Original Research Paper

Curcumin inhibits ox-LDL-induced MCP-1 expression by suppressing the p38MAPK and NF-κB pathways in rat vascular smooth muscle cells

verfasst von: Yi Zhong, Tingrong Liu, Zhigang Guo

Erschienen in: Inflammation Research | Ausgabe 1/2012

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Abstract

Objective

This study was designed to identify the inhibitory effect of curcumin on ox-LDL-induced monocyte chemoattractant protein-1 (MCP-1) production and investigated whether the effects are mediated by mitogen-activated protein kinase (MAPK) and NF-κB pathways in rat vascular smooth muscle cells (VSMCs).

Methods

The VSMCs cells were pretreated with curcumin, before stimulation with ox-LDL. The ox-LDL-induced MCP-1 expression was determined by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Intracellular signaling was investigated by Western blot.

Results

The concentrations of MCP-1 in cell supernatant and were upregulated by ox-LDL in a dose- and time-dependent manner. Additionally, curcumin decreased the expression of MCP-1 in a dose-dependent manner under treatment with ox-LDL (100 μg/ml). Signal transduction studies indicated that the ox-LDL-induced MCP-1 expression in VSMCs could be partly reversed by the inhibitor of p38 MAPK (SB203580) and NF-κB (BAY11-7082), whereas the ERK inhibitor (PD98059) and the JNK inhibitor (SP600125) had no effect. Western blot revealed that curcumin reduced ox-LDL- induced p38 MAPK phosphorylation and nuclear NF-κB p65 protein at the indicated concentration.

Conclusion

Curcumin suppresses ox-LDL-induced MCP-1 expression in VSMCs via the p38 MAPK and NF-κB pathways, which suggests that the anti-inflammatory effect of curcumin is related to the down-regulation of MCP-1 expression and offers a new theoretical basis in the anti-inflammatory effects of curcumin.
Literatur
1.
Zurück zum Zitat Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75(4):787–809.PubMedCrossRef Goel A, Kunnumakkara AB, Aggarwal BB. Curcumin as “Curecumin”: from kitchen to clinic. Biochem Pharmacol. 2008;75(4):787–809.PubMedCrossRef
3.
Zurück zum Zitat Chobanian AV. Single risk factor intervention may be inadequate to inhibit atherosclerosis progression when hypertension and hypercholesterolemia co-exist. Hypertension. 1991;18(2):130–1.PubMed Chobanian AV. Single risk factor intervention may be inadequate to inhibit atherosclerosis progression when hypertension and hypercholesterolemia co-exist. Hypertension. 1991;18(2):130–1.PubMed
4.
Zurück zum Zitat Fogelman A, Schechter I, Seager J, Hokom M, Child JS, Edwards PA. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in macrophages. Proc Natl Acad Sci USA. 1980;77(4):2214–8.PubMedCrossRef Fogelman A, Schechter I, Seager J, Hokom M, Child JS, Edwards PA. Malondialdehyde alteration of low density lipoproteins leads to cholesteryl ester accumulation in macrophages. Proc Natl Acad Sci USA. 1980;77(4):2214–8.PubMedCrossRef
5.
Zurück zum Zitat Reckless J, Rubin E, Verstuyft J, Metcalfe JC, Grainger DJ. Monocyte chemoattractant protein-1, but not tumor necrosis factor is correlated with monocyte infiltration in mouse lipid lesions. Circulation. 1999;99(17):2310–6.PubMed Reckless J, Rubin E, Verstuyft J, Metcalfe JC, Grainger DJ. Monocyte chemoattractant protein-1, but not tumor necrosis factor is correlated with monocyte infiltration in mouse lipid lesions. Circulation. 1999;99(17):2310–6.PubMed
6.
Zurück zum Zitat Wang GP, Deng ZD, Ni J, Qu ZL. Oxidized low density lipoprotein and very low density lipoprotein enhance expression of monocyte chemoattractant protein-1 in rabbit peritoneal exudate macrophages. Atherosclerosis. 1997;133(1):31–6.PubMedCrossRef Wang GP, Deng ZD, Ni J, Qu ZL. Oxidized low density lipoprotein and very low density lipoprotein enhance expression of monocyte chemoattractant protein-1 in rabbit peritoneal exudate macrophages. Atherosclerosis. 1997;133(1):31–6.PubMedCrossRef
7.
Zurück zum Zitat Clarke MC, Talib S, Figg NL, Bennett MR. Vascular smooth muscle cell apoptosis induces interleukin-1-directed inflammation: effects of hyperlipidemia-mediated inhibition of phagocytosis. Circ Res. 2010;106(2):363–72.PubMedCrossRef Clarke MC, Talib S, Figg NL, Bennett MR. Vascular smooth muscle cell apoptosis induces interleukin-1-directed inflammation: effects of hyperlipidemia-mediated inhibition of phagocytosis. Circ Res. 2010;106(2):363–72.PubMedCrossRef
8.
Zurück zum Zitat Navab M, Imes SS, Hama SY, Hough GP, Ross LA, Bork RW, Valente AJ, et al. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest. 1991;88(6):2039–46.PubMedCrossRef Navab M, Imes SS, Hama SY, Hough GP, Ross LA, Bork RW, Valente AJ, et al. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest. 1991;88(6):2039–46.PubMedCrossRef
9.
Zurück zum Zitat Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappa B signaling through a cAMP-dependent pathway. Circulation. 2000;102(11):1296–301.PubMed Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappa B signaling through a cAMP-dependent pathway. Circulation. 2000;102(11):1296–301.PubMed
10.
Zurück zum Zitat Egashira K. Clinical importance of endothelial function in arteriosclerosis and ischemic heart disease. Circ J. 2002;66(6):529–33.PubMedCrossRef Egashira K. Clinical importance of endothelial function in arteriosclerosis and ischemic heart disease. Circ J. 2002;66(6):529–33.PubMedCrossRef
11.
Zurück zum Zitat Usui M, Egashira K, Ohtani K, Kataoka C, Ishibashi M, Hiasa K, Katoh M, et al. Anti-monocyte chemoattractant protein-1 gene therapy inhibits restenotic changes (neointimal hyperplasia) after balloon injury in rats and monkeys. FASEB J. 2002;16(13):1838–40.PubMed Usui M, Egashira K, Ohtani K, Kataoka C, Ishibashi M, Hiasa K, Katoh M, et al. Anti-monocyte chemoattractant protein-1 gene therapy inhibits restenotic changes (neointimal hyperplasia) after balloon injury in rats and monkeys. FASEB J. 2002;16(13):1838–40.PubMed
12.
Zurück zum Zitat Egashira K, Zhao Q, Kataoka C, Ohtani K, Usui M, Charo IF, et al. Importance of monocyte chemoattractant protein-1 pathway in neointimal hyperplasia after periarterial injury in mice and monkeys. Circ Res. 2002;90(11):1167–72.PubMedCrossRef Egashira K, Zhao Q, Kataoka C, Ohtani K, Usui M, Charo IF, et al. Importance of monocyte chemoattractant protein-1 pathway in neointimal hyperplasia after periarterial injury in mice and monkeys. Circ Res. 2002;90(11):1167–72.PubMedCrossRef
13.
Zurück zum Zitat Hokimoto S, Oike Y, Saito T, Kitaoka M, Oshima S, Noda K, et al. Increased expression of monocyte chemoattractant protein-1 in atherectomy specimens from patients with restenosis after percutaneous transluminal coronary angioplasty. Circ J. 2002;66(1):114–6.PubMedCrossRef Hokimoto S, Oike Y, Saito T, Kitaoka M, Oshima S, Noda K, et al. Increased expression of monocyte chemoattractant protein-1 in atherectomy specimens from patients with restenosis after percutaneous transluminal coronary angioplasty. Circ J. 2002;66(1):114–6.PubMedCrossRef
14.
Zurück zum Zitat Kamimura M, Bea F, Akizawa T, Katus HA, Kreuzer J, Viedt C. Platelet-derived growth factor induces tissue factor expression in vascular smooth muscle cells via activation of Egr-1. Hypertension. 2004;44(6):944–51.PubMedCrossRef Kamimura M, Bea F, Akizawa T, Katus HA, Kreuzer J, Viedt C. Platelet-derived growth factor induces tissue factor expression in vascular smooth muscle cells via activation of Egr-1. Hypertension. 2004;44(6):944–51.PubMedCrossRef
15.
Zurück zum Zitat Wallenfeldt K, Fagerberg B, Wikstrand J, Hulthe J. Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men. J Intern Med. 2004;256(5):413–20.PubMedCrossRef Wallenfeldt K, Fagerberg B, Wikstrand J, Hulthe J. Oxidized low-density lipoprotein in plasma is a prognostic marker of subclinical atherosclerosis development in clinically healthy men. J Intern Med. 2004;256(5):413–20.PubMedCrossRef
16.
Zurück zum Zitat Gonçalves I, Gronholdt ML, Söderberg I, Ares MP, Nordestgaard BG, Bentzon JF, et al. Humoral immune response against defined oxidized low-density lipoprotein antigens reflects structure and disease activity of carotid plaques. Arterioscler Thromb Vasc Biol. 2005;25(6):1250–5.PubMedCrossRef Gonçalves I, Gronholdt ML, Söderberg I, Ares MP, Nordestgaard BG, Bentzon JF, et al. Humoral immune response against defined oxidized low-density lipoprotein antigens reflects structure and disease activity of carotid plaques. Arterioscler Thromb Vasc Biol. 2005;25(6):1250–5.PubMedCrossRef
17.
Zurück zum Zitat Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272(34):20963–6.PubMedCrossRef Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272(34):20963–6.PubMedCrossRef
18.
Zurück zum Zitat Rong JX, Berman JW, Taubman MB, Fisher EA. Lysophosphatidylcholine stimulates monocyte chemoattractant protein-1 gene expression in rat aortic smooth muscle cells. Arterioscler Thromb Vasc Biol. 2002;22(10):1617–23.PubMedCrossRef Rong JX, Berman JW, Taubman MB, Fisher EA. Lysophosphatidylcholine stimulates monocyte chemoattractant protein-1 gene expression in rat aortic smooth muscle cells. Arterioscler Thromb Vasc Biol. 2002;22(10):1617–23.PubMedCrossRef
19.
Zurück zum Zitat Geng H, Wang A, Rong G, Zhu B, Deng Y, Chen J, et al. The effects of ox-LDL in human atherosclerosis may be mediated in part via the toll-like receptor 4 pathway. Mol Cell Biochem. 2010;342(1–2):201–6.PubMedCrossRef Geng H, Wang A, Rong G, Zhu B, Deng Y, Chen J, et al. The effects of ox-LDL in human atherosclerosis may be mediated in part via the toll-like receptor 4 pathway. Mol Cell Biochem. 2010;342(1–2):201–6.PubMedCrossRef
20.
Zurück zum Zitat Jing Q, Xin SM, Cheng ZJ, Zhang WB, Zhang R, Qin YW, et al. Activation of p38 mitogen-activated protein kinase by oxidized LDL in vascular smooth muscle cells: mediation via pertussis toxin-sensitive G proteins and association with oxidized LDL-induced cytotoxicity. Circ Res. 1999;84(7):831–9.PubMed Jing Q, Xin SM, Cheng ZJ, Zhang WB, Zhang R, Qin YW, et al. Activation of p38 mitogen-activated protein kinase by oxidized LDL in vascular smooth muscle cells: mediation via pertussis toxin-sensitive G proteins and association with oxidized LDL-induced cytotoxicity. Circ Res. 1999;84(7):831–9.PubMed
21.
Zurück zum Zitat Wang WY, Li J, Yang D, Xu W, Zha RP, et al. Ox-LDL stimulates lipoprotein-associated phospholipase A2 expression in THP-1 monocytes via PI3 K and p38 MAPK pathways. Circ Res. 2010;85(4):845–52. Wang WY, Li J, Yang D, Xu W, Zha RP, et al. Ox-LDL stimulates lipoprotein-associated phospholipase A2 expression in THP-1 monocytes via PI3 K and p38 MAPK pathways. Circ Res. 2010;85(4):845–52.
22.
Zurück zum Zitat Sun Y, Chen X (2010) Ox-LDL-induced LOX-1 expression in vascular smooth muscle cells: role of reactive oxygen species. Fundam Clin Pharmacol. doi:10.1111/j.1472-8206.2010.00885.x (Epub ahead of print). Sun Y, Chen X (2010) Ox-LDL-induced LOX-1 expression in vascular smooth muscle cells: role of reactive oxygen species. Fundam Clin Pharmacol. doi:10.​1111/​j.​1472-8206.2010.00885.x (Epub ahead of print).
23.
Zurück zum Zitat Hong MH, Kim MH, Chang HJ, Kim NH, Shin BA, Ahn BW, et al. (−)-Epigallocatechin-3-gallate inhibits monocyte chemotactic protein-1 expression in endothelial cells via blocking NF-kappaB signaling. Life Sci. 2007;80(21):1957–65.PubMedCrossRef Hong MH, Kim MH, Chang HJ, Kim NH, Shin BA, Ahn BW, et al. (−)-Epigallocatechin-3-gallate inhibits monocyte chemotactic protein-1 expression in endothelial cells via blocking NF-kappaB signaling. Life Sci. 2007;80(21):1957–65.PubMedCrossRef
24.
Zurück zum Zitat Takaya K, Koya D, Isono M, Sugimoto T, Sugaya T, Kashiwagi A, et al. Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells. Am J Physiol Renal Physiol. 2003;284(5):1037–45. Takaya K, Koya D, Isono M, Sugimoto T, Sugaya T, Kashiwagi A, et al. Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells. Am J Physiol Renal Physiol. 2003;284(5):1037–45.
25.
Zurück zum Zitat Lim JH, Kwon TK. Curcumin inhibits phorbol myristate acetate (PMA)-induced MCP-1 expression by inhibiting ERK and NF-kappaB transcriptional activity. Food Chem Toxicol. 2010;48(1):47–52.PubMedCrossRef Lim JH, Kwon TK. Curcumin inhibits phorbol myristate acetate (PMA)-induced MCP-1 expression by inhibiting ERK and NF-kappaB transcriptional activity. Food Chem Toxicol. 2010;48(1):47–52.PubMedCrossRef
Metadaten
Titel
Curcumin inhibits ox-LDL-induced MCP-1 expression by suppressing the p38MAPK and NF-κB pathways in rat vascular smooth muscle cells
verfasst von
Yi Zhong
Tingrong Liu
Zhigang Guo
Publikationsdatum
01.01.2012
Verlag
SP Birkhäuser Verlag Basel
Erschienen in
Inflammation Research / Ausgabe 1/2012
Print ISSN: 1023-3830
Elektronische ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-011-0389-3

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