Increased expression of interleukin-1β in triglyceride-induced macrophage cell death is mediated by p38 MAP kinase
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Triglycerides (TG) are implicated in the development of atherosclerosis through formation of foam cells and induction of macrophage cell death. In this study, we report that addition of exogenous TG induced cell death in phorbol 12-myristate 13-acetate-differentiated THP-1 human macrophages. TG treatment induced a dramatic decrease in interleukin-1β (IL-1β)mRNA expression in a dose- and time-dependent manner. The expression of granulocyte macrophage colony-stimulating factor and platelet endothelial cell adhesion molecule remained unchanged. To identify signaling pathways involved in TGinduced downregulation of IL-1β, we added p38 MAPK, protein kinase C (PKC) or c-Raf1 specific inhibitors. We found that inhibition of p38 MAPK alleviated the TG-induced downregulation of IL-1β, whereas inhibition of PKC and c-Raf1 had no effect. This is the first report showing decreased IL-1β expression during TG-induced cell death in a human macrophage line. Our results suggest that downregulation of IL-1β expression by TG-treated macrophages may play a role during atherogenesis. [BMB Reports 2012; 45(7): 414-418]
Abstract
Triglycerides (TG) are implicated in the development of atherosclerosis through formation of foam cells and induction of macrophage cell death. In this study, we report that addition of exogenous TG induced cell death in phorbol 12-myristate 13-acetate-differentiated THP-1 human macrophages. TG treatment induced a dramatic decrease in interleukin-1β (IL-1β)mRNA expression in a dose- and time-dependent manner. The expression of granulocyte macrophage colony-stimulating factor and platelet endothelial cell adhesion molecule remained unchanged. To identify signaling pathways involved in TGinduced downregulation of IL-1β, we added p38 MAPK, protein kinase C (PKC) or c-Raf1 specific inhibitors. We found that inhibition of p38 MAPK alleviated the TG-induced downregulation of IL-1β, whereas inhibition of PKC and c-Raf1 had no effect. This is the first report showing decreased IL-1β expression during TG-induced cell death in a human macrophage line. Our results suggest that downregulation of IL-1β expression by TG-treated macrophages may play a role during atherogenesis. [BMB Reports 2012; 45(7): 414-418]
참고문헌 (34)
- Jong-Gil Park, "The role of peroxidases in the pathogenesis of atherosclerosis", BMB Reports, 44(8), pp.497~505 (2011), 생화학분자생물학회
- Ross, R., "Atherosclerosis--an inflammatory disease", N. Engl. J. Med., 340, pp.115~126 (1999)
- Vorchheimer, D. A., "Inflammatory markers in coronary artery disease: let prevention douse the flames", JAMA, 286, pp.2154~2156 (2001)
- Elgharib, N., "C-reactive protein as a novel biomarker. Reactant can flag atherosclerosis and help predict cardiac events", Postgrad. Med., 114, pp.39~44 (2003)
- Smith, J. D., "Decreased atherosclerosis in mice deficient in both macrophage colony-stimulating factor (op) and apolipoprotein E", Proc. Natl. Acad. Sci. U.S.A., 92, pp.8264~8268 (1995)
- Boring, L., "Decreased lesion formation in CCR2-", - mice reveals a role for chemokines in the initiation of atherosclerosis, 1998, pp.394, 894~897
- Sofer, O., "Regulation of lipoprotein lipase secretion in murine macrophages during foam cell formation in vitro. Effect of triglyceride- rich lipoproteins", Arterioscler. Thromb., 12, pp.1458~1466 (1992)
- Rosenblat, M., "Paraoxonase 2 attenuates macrophage triglycerideaccumulation via inhibition of diacylglycerol acyltransferase1", J. Lipid. Res., 50, pp.870~879 (2009)
- Aronis, A., "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, pp.1221~1230 (2005)
- Aronis, A., "Lipotoxic effects of triacylglycerols in J774.2 macrophages", Nutrition, 24, pp.167~176 (2008)
- Tabas, I., "Apoptosis and plaque destabilization in atherosclerosis: the role of macrophage apoptosis induced by cholesterol", Cell Death Differ., 11(Suppl 1), pp.S12~S16 (2004)
- Nhan, T. Q., "Role of caspases in death and survival of the plaque macrophage", Arterioscler. Thromb. Vasc. Biol., 25, pp.895~903 (2005)
- Kockx, M. M., "Apoptosis in the atherosclerotic plaque: quantitative and qualitative aspects", Arterioscler. Thromb. Vasc. Biol., 18, pp.1519~1522 (1998)
- Henson, P. M., "Apoptotic cell removal", Curr. Biol., 11, pp.R795~R805 (2001)
- Savill, J., "Corpse clearance defines the meaning of cell death", Nature, 407, pp.784~788 (2000)
- Majno, G., "Apoptosis, oncosis, and necrosis. An overview of cell death", Am. J. Pathol., 146, pp.3~15 (1995)
- Fink, S. L., "Apoptosis, pyroptosis, and necrosis: mechanistic description of dead and dying eukaryotic cells", Infect. Immun., 73, pp.1907~1916 (2005)
- Tabas, I., "Consequences and therapeutic implications of macrophage apoptosis in atherosclerosis: the importance of lesion stage and phagocytic efficiency", Arterioscler. Thromb. Vasc. Biol., 25, pp.2255~2264 (2005)
- Norata, G. D., "Gene expression and intracellular pathways involved in endothelial dysfunction induced by VLDL and oxidised VLDL", Cardiovasc. Res., 59, pp.169~180 (2003)
- Tedgui, A., "Cytokines in atherosclerosis: pathogenic and regulatory pathways", Physiol. Rev., 86, pp.515~581 (2006)
- Ait-Oufella, H., "Recent advances on the role of cytokines in atherosclerosis", Arterioscler. Thromb. Vasc. Biol., 31, pp.969~979 (2011)
- Stoneman, V. E., "Role of apoptosis in atherosclerosis and its therapeutic implications", Clin. Sci., 107, pp.343~354 (2004)
- Verma, G., "IL-1beta induces ER stress in a JNK dependent manner that determines cell death in human pancreatic epithelial MIA PaCa-2 cells", Apoptosis, 15, pp.864~876 (2010)
- Zhu, S. N., "GM-CSF regulates intimal cell proliferation in nascentatherosclerotic lesions", J. Exp. Med., 206, pp.2141~2149 (2009)
- Harry, B. L., "Endothelial cell PECAM-1 promotes atherosclerotic lesions in areas of disturbed flow in ApoE-deficient mice", Arterioscler. Thromb. Vasc. Biol., 28, pp.2003~2008 (2008)
- Aflaki, E., "Triacylglycerol accumulation activates the mitochondrial apoptosis pathway in macrophages", J. Biol. Chem., 286, pp.7418~7428 (2011)
- Messmer, U. K., "Bcl-2 protects macrophages from nitric oxide-induced apoptosis", J. Biol. Chem., 271, pp.20192~20197 (1996)
- Kim, H. J., "PPARdelta inhibits IL-1beta-stimulated proliferation and migration of vascular smooth muscle cells via up-regulation of IL-1Ra", Cell Mol. Life Sci., 67, pp.2119~2130 (2010)
- Stintzing, S., "Differentiation patterning of vascular smooth muscle cells (VSMC) in atherosclerosis", Virchows. Arch., 455, pp.171~185 (2009)
- Clarke, M. C., "Vascular smooth muscle cell apoptosis induces interleukin-1-directed inflammation: effects of hyperlipidemia-mediated inhibition of phagocytosis", Circ. Res., 106, pp.363~372 (2010)
- Han, J., "A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells", Science, 265, pp.808~811 (1994)
- Krauss, R. S., "The role of protein kinase C in signal transduction and cellular transformation", Prog. Clin. Biol. Res., 340D, pp.175~182 (1990)
- Peyssonnaux, C., "The Raf", MEK, Biol. Cell, pp.2001, 93[DOI]
- Young-Ok Son, "Over-expression of JunB inhibits mitochondrial stress and cytotoxicity in human lymphoma cells exposed to chronic oxidative stress", BMB reports, 43(1), pp.57~61 (2010), 한국생화학분자생물학회