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Genes & Genomics

, Volume 35, Issue 1, pp 125–130 | Cite as

Triglyceride (TG) down-regulates expression of MCP-1 and CCR2 in PMA-derived THP-1 macrophages

  • Yoon Suk Kim
  • Ho Joong Sung
  • Sin Jee Son
  • Jaewon Lim
  • Yeo Wool Kang
  • Tae Ue Kim
  • Ki-Jong RheeEmail author
Research Article

Abstract

Triglycerides (TGs) are implicated in the development of atherosclerosis. A key contributing factor for atherosclerosis is the migration of macrophages to atherosclerotic lesions. MCP-1 is a major chemoattractant for macrophages to atherosclerotic lesions. We examined the expression profile of MCP-1 and CCR2 in THP-1 macrophages in response to TG treatment by RT-PCR analysis. Chemical inhibitors were used to identify cell signaling pathway(s) involved in regulation of MCP-1 and CCR2 expression. We found that treatment of THP-1 macrophages with TG down-regulated MCP-1 expression in a time and dose-dependent manner. PMA treatment alone did not affect MCP-1 expression. Using chemical inhibitors of cell signaling pathways, we found that the NF-κB inhibitor inhibited TG-induced down-regulation of MCP-1. CCR2 expression decreased after TG treatment in THP-1 macrophages and the PKC inhibitor alleviated TG-induced down-regulation of CCR2. Our results provide further insights into the role of TG on macrophages during atherosclerosis.

Keywords

Triglyceride Macrophage MCP-1 CCR2 Cell signaling Atherosclerosis 

Notes

Conflict of interest

The authors declare no conflicts of interest.

References

  1. Aronis A, Madar Z, Tirosh O (2005) Mechanism underlying oxidative stress-mediated lipotoxicity: exposure of J774.2 macrophages to triacylglycerols facilitates mitochondrial reactive oxygen species production and cellular necrosis. Free Radic Biol Med 38:1221–1230PubMedCrossRefGoogle Scholar
  2. Aronis A, Madar Z, Tirosh O (2008) Lipotoxic effects of triacylglycerols in J774.2 macrophages. Nutrition 24:167–176PubMedCrossRefGoogle Scholar
  3. Boring L, Gosling J, Cleary M, Charo IF (1998) Decreased lesion formation in CCR2−/− mice reveals a role for chemokines in the initiation of atherosclerosis. Nature 394:894–897PubMedCrossRefGoogle Scholar
  4. Dawson TC, Kuziel WA, Osahar TA, Maeda N (1999) Absence of CC chemokine receptor-2 reduces atherosclerosis in apolipoprotein E-deficient mice. Atherosclerosis 143:205–211PubMedCrossRefGoogle Scholar
  5. Donadelli R, Abbate M, Zanchi C, Corna D, Tomasoni S, Benigni A, Remuzzi G, Zoja C (2000) Protein traffic activates NF-kB gene signaling and promotes MCP-1-dependent interstitial inflammation. Am J Kidney Dis 36:1226–1241PubMedCrossRefGoogle Scholar
  6. Geurian K, Pinson JB, Weart CW (1992) The triglyceride connection in atherosclerosis. Ann Pharmacother 26:1109–1117PubMedGoogle Scholar
  7. Lim JH, Kwon TK (2010) Curcumin inhibits phorbol myristate acetate (PMA)-induced MCP-1 expression by inhibiting ERK and NF-kappaB transcriptional activity. Food Chem Toxicol 48:47–52PubMedCrossRefGoogle Scholar
  8. Malloy MJ, Kane JP (2001) A risk factor for atherosclerosis: triglyceride-rich lipoproteins. Adv Intern Med 47:111–136PubMedGoogle Scholar
  9. Nelken NA, Coughlin SR, Gordon D, Wilcox JN (1991) Monocyte chemoattractant protein-1 in human atheromatous plaques. J Clin Invest 88:1121–1127PubMedCrossRefGoogle Scholar
  10. Park JG, Oh GT (2011) The role of peroxidases in the pathogenesis of atherosclerosis. BMB Rep 44:497–505PubMedCrossRefGoogle Scholar
  11. Ross R (1999) Atherosclerosis—an inflammatory disease. N Engl J Med 340:115–126PubMedCrossRefGoogle Scholar
  12. Seino Y, Ikeda U, Takahashi M, Hojo Y, Irokawa M, Kasahara T, Shimada K (1995) Expression of monocyte chemoattractant protein-1 in vascular tissue. Cytokine 7:575–579PubMedCrossRefGoogle Scholar
  13. Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J, Miyata M (1995) Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E. Proc Natl Acad Sci USA 92:8264–8268PubMedCrossRefGoogle Scholar
  14. Sofer O, Fainaru M, Schafer Z, Goldman R (1992) Regulation of lipoprotein lipase secretion in murine macrophages during foam cell formation in vitro. Effect of triglyceride-rich lipoproteins. Arterioscler Thromb 12:1458–1466PubMedCrossRefGoogle Scholar
  15. Son YK, da Hong H, Kim DJ, Firth AL, Park WS (2011) Direct effect of protein kinase C inhibitors on cardiovascular ion channels. BMB Rep 44:559–565PubMedCrossRefGoogle Scholar
  16. Sung HJ, Son SJ, Yang SJ, Rhee KJ, Kim YS (2012) Increased expression of interleukin-1beta in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase. BMB Rep 45:414–418PubMedCrossRefGoogle Scholar
  17. Takeya M, Yoshimura T, Leonard EJ, Takahashi K (1993) Detection of monocyte chemoattractant protein-1 in human atherosclerotic lesions by an anti-monocyte chemoattractant protein-1 monoclonal antibody. Hum Pathol 24:534–539PubMedCrossRefGoogle Scholar
  18. Tousoulis D, Davies G, Stefanadis C, Toutouzas P, Ambrose JA (2003) Inflammatory and thrombotic mechanisms in coronary atherosclerosis. Heart 89:993–997PubMedCrossRefGoogle Scholar
  19. Ueda A, Okuda K, Ohno S, Shirai A, Igarashi T, Matsunaga K, Fukushima J, Kawamoto S, Ishigatsubo Y, Okubo T (1994) NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene. J Immunol 153:2052–2063PubMedGoogle Scholar
  20. Vorchheimer DA, Fuster V (2001) Inflammatory markers in coronary artery disease: let prevention douse the flames. JAMA 286:2154–2156PubMedCrossRefGoogle Scholar
  21. Wang Y, Zhang W, Li S, Song W, Chen J, Hui R (2011) Genetic variants of the monocyte chemoattractant protein-1 gene and its receptor CCR2 and risk of coronary artery disease: a meta-analysis. Atherosclerosis 219:224–230PubMedCrossRefGoogle Scholar
  22. Yla-Herttuala S, Lipton BA, Rosenfeld ME, Sarkioja T, Yoshimura T, Leonard EJ, Witztum JL, Steinberg D (1991) Expression of monocyte chemoattractant protein 1 in macrophage-rich areas of human and rabbit atherosclerotic lesions. Proc Natl Acad Sci USA 88:5252–5256PubMedCrossRefGoogle Scholar

Copyright information

© The Genetics Society of Korea 2013

Authors and Affiliations

  • Yoon Suk Kim
    • 1
  • Ho Joong Sung
    • 2
  • Sin Jee Son
    • 1
  • Jaewon Lim
    • 1
  • Yeo Wool Kang
    • 1
  • Tae Ue Kim
    • 1
  • Ki-Jong Rhee
    • 1
    Email author
  1. 1.Department of Biomedical Laboratory Science, College of Health SciencesYonsei UniversityGangwon-doRepublic of Korea
  2. 2.Department of Biomedical Laboratory Science, College of Health ScienceEulji UniversityGyeongi-DoRepublic of Korea

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