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Trans-10, cis-12 Conjugated Linoleic Acid Modulates Tumor Necrosis Factor-${\alpha}$ Production and Nuclear Factor-${\kappa}B$ Activation in RAW 264.7 Macrophages Through Formation of Reactive Oxygen Species  

Park, So-Young (Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University)
Kang, Byeong-Teck (Laboratory of Veterinary Dermatology, Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University)
Kang, Ji-Houn (Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University)
Yang, Mhan-Pyo (Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University)
Publication Information
Journal of Veterinary Clinics / v.31, no.6, 2014 , pp. 469-476 More about this Journal
Abstract
The aims of this study were to explore the effects of conjugated linoleic acid (CLA) on reactive oxygen species (ROS) production in lipopolysaccharide (LPS)-naïve and LPS-stimulated RAW 264.7 macrophages and to examine whether these effects affect the regulation of tumor necrosis factor-alpha (TNF-${\alpha}$) production, and nuclear factor-kappa B (NF-${\kappa}B$) and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) activation. Trans-10, cis-12(t10c12)-CLA increased the production of ROS, as well as TNF-${\alpha}$ in LPS-naïve RAW 264.7 cells. The CLA-induced TNF-${\alpha}$ production was suppressed by treatment of diphenyleneiodonium chloride (DPI), a NADPH oxidase inhibitor. In addition, CLA enhanced the activities of NF-${\kappa}B$ and $PPAR{\gamma}$ in LPS-naïve RAW 264.7 cells, and this effect was abolished with DPI treatment. LPS treatment increased ROS production, whereas CLA reduced LPS-induced ROS production. LPS increased both TNF-${\alpha}$ production and NF-${\kappa}B$ activity, whereas t10c12-CLA reduced TNF-${\alpha}$ production and NF-${\kappa}B$ activity in LPS-stimulated RAW 264.7 cells. DPI treatment suppressed LPS-induced ROS production and NF-${\kappa}B$ activity. Moreover, DPI enhanced the inhibitory effects of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ activation in LPS-stimulated RAW 264.7 cells. However, neither t10c12-CLA nor DPI affected $PPAR{\gamma}$ activity in LPS-stimulated RAW 264.7 cells. Taken together, these data indicate that t10c12-CLA induces TNF-${\alpha}$ production by increasing ROS production in LPS-naïve RAW 264.7 cells, which is mediated by the enhancement of NF-${\kappa}B$ activity via $PPAR{\gamma}$ activation. By contrast, t10c12-CLA suppresses TNF-${\alpha}$ production by inhibiting ROS production and NF-${\kappa}B$ activation via a $PPAR{\gamma}$-independent pathway in LPS-stimulated RAW 264.7 cells. These results suggest that t10c12-CLA can modulate TNF-${\alpha}$ production and NF-${\kappa}B$ activation through formation of ROS in RAW 264.7 macrophages.
Keywords
conjugated linoleic acid(CLA); lipopolysaccharide(LPS); tumor necrosis factor-alpha(TNF-${\alpha}$); nuclear factor-kappa B(NF-${\kappa}B$); reactive oxygen species(ROS); peroxisome proliferator-activated receptor gamma($PPAR{\gamma}$); RAW 264.7 macrophages;
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1 Bai XC, Lu D, Liu AL Zhang ZM, Li XM, Zou ZP, Zeng WS, Cheng BL, Luo SQ. Reactive oxygen species stimulates receptor activator of NF-kappaB ligand expression in osteoblast. J Biol Chem 2005; 280: 17497-17506.   DOI   ScienceOn
2 Belury MA. Dietary conjugated linoleic acid in health: physiological effects and mechanisms of action. Annu Rev Nutr 2002; 22: 505-531.   DOI   ScienceOn
3 Belury MA. Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. J Nutr 2002; 132: 2995-2998.   DOI
4 Changhua L, Jindong Y, Defa L, Lidan Z, Shiyan Q, Jianjun X. Conjugated linoleic acid attenuates the production and gene expression of proinflammatory cytokines in weaned pigs challenged with lipopolysaccharide. J Nutr 2005; 135: 239-244.   DOI
5 Chung S, Brown JM, Provo JN, Hopkins R, McIntosh MK. Conjugated linoleic acid promotes human adipocyte insulin resistance through NF$\kappa$B-dependent cytokine production. J Biol Chem 2005; 280: 38445-38456.   DOI   ScienceOn
6 Granlund L, Juvet LK, Pedersen JI, Nebb HI. Trans10, cis12- conjugated linoleic acid prevents triacylglycerol accumulation in adipocytes by acting as a PPARgamma modulator. J Lipid Res 2003; 44: 1441-1452.   DOI   ScienceOn
7 Halliwell B, Gutteridge JM. Role of free radicals and catalytic metal ions in human disease: an overview. Methods Enzymol 1990; 186: 1-85.   DOI
8 Hassan Eftekhari M, Aliasghari F, Babaei-Beigi MA, Hasanzadeh J. Effect of conjugated linoleic acid and omega-3 fatty acid supplementation on inflammatory and oxidative stress markers in atherosclerotic patients. ARYA Atheroscler 2013; 9: 311-318.
9 Houseknecht KL, Vanden Heuvel JP, Moya-Camarena SY, et al.: Dietary conjugated linoleic acid normalizes impaired glucose tolerance in the Zucker diabetic fatty fa/fa rat. Biochem Biophys Res Commun 1998; 244: 678-682.   DOI   ScienceOn
10 Hu X. Proteolytic signaling by TNFalpha: caspase activation and IkappaB degradation. Cytokine 2003; 21: 286-294.   DOI
11 Kim DI, Kim KH, Kang JH, Jung EM, Kim SS, Jeung EB, Yang MP. Trans-10, cis-12-conjugated linoleic acid modulates NF-$\kappa$B activation and TNF-$\alpha$ production in porcine peripheral blood mononuclear cells via a PPAR$\gamma$- dependent pathway. Br J Nutr 2011; 105: 1329-1336.   DOI
12 Kim YS, Morgan MJ, Choksi S, Liu ZG. TNF-induced activation of the Nox1 NADPH oxidase and its role in the induction of necrotic cell death. Mol Cell 2007; 26: 675-687.   DOI   ScienceOn
13 Kritchevsky D, Tepper SA, Wright S, Czarnecki SK, Wilson TA, Nicolosi RJ. Conjugated linoleic acid isomer effects in atherosclerosis: growth and regression of lesions. Lipids 2004; 39: 611-616.   DOI   ScienceOn
14 Nakamura YK, Omaye ST. Conjugated linoleic acid isomers' roles in the regulation of PPAR-gamma and NF-kappaB DNA binding and subsequent expression of antioxidant enzymes in human umbilical vein endothelial cells. Nutrition 2009; 25: 800-811.   DOI
15 Lee MJ, Kang BT, Kang JH, Yang MP. Effect of Conjugated Linoleic Acid on Nuclear Factor-$\kappa$B Activation and Tumor Necrosis Factor-$\alpha$ Production in RAW 264.7 Cells Exposed to High Concentration of Glucose. J Vet Clin 2012; 10: 361-367.
16 Li G, Barnes D, Butz D, Bjorling D, Cook ME. 10t,12cconjugated linoleic acid inhibits lipopolysaccharide-induced cyclooxygenase expression in vitro and in vivo. J Lipid Res 2005; 46: 2134-2142.   DOI   ScienceOn
17 Morgan MJ, Liu ZG. Crosstalk of reactive oxygen species and NF-$\kappa$B signaling. Cell Res 2011; 21: 103-115.   DOI   ScienceOn
18 Park NY, Valacchi G, Lim Y. Effect of dietary conjugated linoleic acid supplementation on early inflammatory responses during cutaneous wound healing. Mediators Inflamm 2010; 2010: 342328.
19 Petrova TV, Akama KT, Van Eldik LJ. Cyclopentenone prostaglandins suppress activation of microglia: down-regulation of inducible nitric-oxide synthase by 15-deoxy- Delta12,14-prostaglandin J2. Proc Natl Acad Sci U S A 1999; 96: 4668-4673.   DOI
20 Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor-gamma is a negative regulator of macrophage activation. Nature 1998; 391: 79-82.   DOI   ScienceOn
21 Ringseis R, Müller A, Herter C, Gahler S, Steinhart H, Eder K. CLA isomers inhibit TNFalpha-induced eicosanoid release from human vascular smooth muscle cells via a PPARgamma ligand-like action. Biochim Biophys Acta 2006; 1760: 290-300.   DOI   ScienceOn
22 Staal FJ, Roederer M, Herzenberg LA, Herzenberg LA. Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. Proc Natl Acad Sci U S A 1990; 87: 9943-9947.   DOI   ScienceOn
23 Schoonbroodt S, Legrand-Poels S, Best-Belpomme M, Piette J. Activation of the NF-kappaB transcription factor in a Tlymphocytic cell line by hypochlorous acid. Biochem J 1997; 321: 777-785.   DOI
24 Shang FJ, Wang JP, Zheng QS, Liu XT, Xue YS, Li J, Zhao LY. The relationship between reactive oxygen speciesdependent activation of p38 MAPK and the expression of tumor necrosis factor-$\alpha$ in cultured cardiomyocytes. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2011; 27: 7-10.
25 Song DH, Kang JH, Lee GS, Jeung EB, Yang MP. Upregulation of tumor necrosis factor-alpha expression by trans10-cis12 conjugated linoleic acid enhances phagocytosis of RAW macrophages via a peroxisome proliferator-activated receptor gamma-dependent pathway. Cytokine 2007; 37: 227-235.   DOI   ScienceOn
26 Taylor JS, Williams SR, Rhys R, James P, Frenneaux MP. Conjugated linoleic acid impairs endothelial function. Arterioscler Thromb Vasc Biol 2006; 26: 307-312.
27 Verstrepen L, Bekaert T, Chau TL, Tavernier J, Chariot A, Beyaert R. TLR-4, IL-1R and TNF-R signaling to NFkappaB: variations on a common theme. Cell Mol Life Sci 2008; 65: 2964-2978.   DOI
28 Wright G, Singh IS, Hasday JD, Farrance IK, Hall G, Cross AS, Rogers TB. Endotoxin stress-response in cardiomyocytes: NF-kappaB activation and tumor necrosis factor-alpha expression. Am J Physiol Heart Circ Physiol 2002; 282: H872-879.   DOI
29 Yu Y, Correll PH, Vanden Heuvel JP. Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism. Biochim Biophys Acta 2002; 1581: 89-99.   DOI   ScienceOn
30 Yang M, Cook ME. Dietary conjugated linoleic acid decreased cachexia, macrophage tumor necrosis factor-alpha production, and modifies splenocyte cytokines production. Exp Biol Med (Maywood) 2003; 228: 51-58.   DOI
31 Zhu W, Downey JS, Gu J, Di Padova F, Gram H, Han J. Regulation of TNF expression by multiple mitogen-activated protein kinase pathways. J Immunol 2000; 164: 6349-6358.   DOI
32 Stachowska E, Ba kiewicz-Masiuk M, Dziedziejko V, Gutowska I, Baranowska-Bosiacka I, Marchlewicz M, Do egowska B, Wiszniewska B, Machali ski B, Chlubek D. Conjugated linoleic acid increases intracellular ROS synthesis and oxygenation of arachidonic acid in macrophages. Nutrition 2008; 24: 187-199.   DOI
33 Cook ME, Miller CC, Park Y, Pariza M. Immune modulation by altered nutrient metabolism: nutritional control of immuneinduced growth depression. Poult Sci 1993; 72: 1301-1305.   DOI   ScienceOn
34 Kim KH, Kim DI, Kim SH, Jung EM, Kang JH, Jeung EB, Yang MP. Trans-10, cis-12-conjugated linoleic acid attenuates tumor necrosis factor-$\alpha$ production by lipopolysaccharide- stimulated porcine peripheral blood mononuclear cells through induction of interleukin-10. Cytokine 2011; 56: 224-230.   DOI
35 Loscher CE, Draper E, Leavy O, Kelleher D, Mills KH, Roche HM. Conjugated linoleic acid suppresses NF-kappa B activation and IL-12 production in dendritic cells through ERK-mediated IL-10 induction. J Immunol 2005; 175: 4990-4998.   DOI
36 Zhao L, Yin J, Li D, Lai C, Chen X, Ma D. Conjugated linoleic acid can prevent tumor necrosis factor gene expression by inhibiting nuclear factor binding activity in peripheral blood mononuclear cells from weaned pigs challenged with lipopolysaccharide. Arch Anim Nutr 2005; 59: 429-438.   DOI   ScienceOn