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Trans-10, cis-12-conjugated linoleic acid modulates NF-κB activation and TNF-α production in porcine peripheral blood mononuclear cells via a PPARγ-dependent pathway

  • Dong-In Kim (a1), Keun-Hwa Kim (a1), Ji-Houn Kang (a1), Eui-Man Jung (a2), Sung-Soo Kim (a1), Eui-Bae Jeung (a2) and Mhan-Pyo Yang (a1)...

Abstract

The activation of PPARγ by ligands, including conjugated linoleic acid (CLA) isomers, plays an important role in the immune response. Among CLA isomers, trans-10, cis-12 (t10c12)-CLA is known to participate in the modulation of pro-inflammatory cytokine secretion. The aim of the present study was to assess the effect of t10c12-CLA on PPARγ activation, NF-κB activation and TNF-α expression in lipopolysaccharide (LPS)-naive and LPS-stimulated porcine peripheral blood mononuclear cells (PBMC). In addition, the effect of PPARγ inhibition on NF-κB activation and TNF-α expression in porcine PBMC was examined. t10c12-CLA was found to increase TNF-α expression and NF-κB activity in LPS-naive porcine PBMC. In contrast, t10c12-CLA decreased TNF-α expression and NF-κB activity in LPS-stimulated porcine PBMC. t10c12-CLA up-regulated PPARγ activity and mRNA expression in both LPS-naive and LPS-stimulated porcine PBMC. GW9662, a PPARγ antagonist, completely negated the modulating effects of t10c12-CLA on TNF-α expression and NF-κB activity in both LPS-naive and LPS-stimulated porcine PBMC. These results suggest that t10c12-CLA can modulate TNF-α production and NF-κB activation by a PPARγ-dependent pathway in porcine PBMC.

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Corresponding author

*Corresponding author: Professor M.-P. Yang, fax +82 43 261 3224, email mpyang@chungbuk.ac.kr

References

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1Pariza, MW & Ha, YL (1990) Conjugated dienoic derivatives of linoleic acid: a new class of anticarcinogens. Med Oncol Tumor Pharmacother 7, 169171.
2Smedman, A & Vessby, B (2001) Conjugated linoleic acid supplementation in humans – metabolic effects. Lipids 36, 773781.
3Ryder, JW, Portocarrero, CP, Song, XM, et al. (2001) Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes 50, 11491157.
4Watkins, BA & Seifert, MF (2000) Conjugated linoleic acid and bone biology. J Am Coll Nutr 19, 478486.
5Palombo, JD, Ganguly, A, Bistrian, BR, et al. (2002) The antiproliferative effects of biologically active isomers of conjugated linoleic acid on human colorectal and prostatic cancer cells. Cancer Lett 177, 163172.
6Lee, KN, Kritchevsky, D & Pariza, MW (1994) Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108, 1925.
7Bhattacharya, A, Banu, J, Rahman, M, et al. (2006) Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem 17, 789810.
8Yamasaki, M, Kishihara, K, Mansho, K, et al. (2000) Dietary conjugated linoleic acid increases immunoglobulin productivity of Sprague–Dawley rat spleen lymphocytes. Biosci Biotechnol Biochem 64, 21592164.
9Cho, MH, Kang, JH & Yang, MP (2008) Immunoenhancing effect of trans-10, cis-12 conjugated linoleic acid on the phagocytic capacity and oxidative burst activity of canine peripheral blood phagocytes. Res Vet Sci 85, 269278.
10Yu, Y, Correll, PH & Vanden Heuvel, JP (2002) Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism. Biochim Biophys Acta 1581, 8999.
11Daynes, RA & Jones, DC (2002) Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol 2, 748759.
12Jiang, C, Ting, AT & Seed, B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391, 8286.
13Changhua, L, Jindong, Y, Defa, L, et al. (2005) Conjugated linoleic acid attenuates the production and gene expression of proinflammatory cytokines in weaned pigs challenged with lipopolysaccharide. J Nutr 135, 239244.
14Ji, JD, Kim, HJ, Rho, YH, et al. (2005) Inhibition of IL-10-induced STAT3 activation by 15-deoxy-Delta12,14-prostaglandin J2. Rheumatology 44, 983988.
15Ghosh, S & Karin, M (2002) Missing pieces in the NF-kappaB puzzle. Cell 109, 8196.
16Verma, IM, Stevenson, JK, Schwarz, EM, et al. (1995) Rel/NF-kappa B/I kappa B family: intimate tales of association and dissociation. Genes Dev 9, 27232735.
17Meldrum, DR (1998) Tumor necrosis factor in the heart. Am J Physiol 274, 577595.
18Wright, G, Singh, IS, Hasday, JD, et al. (2002) Endotoxin stress-response in cardiomyocytes: NF-kappaB activation and tumor necrosis factor-alpha expression. Am J Physiol Heart Circ Physiol 282, 872879.
19Chen, GG, Lee, JF, Wang, SH, et al. (2002) Apoptosis induced by activation of peroxisome-proliferator activated receptor-gamma is associated with Bcl-2 and NF-kappaB in human colon cancer. Life Sci 70, 26312646.
20Ringseis, R, Gahler, S, Herter, C, et al. (2006) Conjugated linoleic acids exert similar actions on prostanoid release from aortic and coronary artery smooth muscle cells. Int J Vitam Nutr Res 76, 281289.
21Tsuboyama-Kasaoka, N, Takahashi, M, Tanemura, K, et al. (2000) Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 49, 15341542.
22Poirier, H, Shapiro, JS, Kim, RJ, et al. (2006) Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue. Diabetes 55, 16341641.
23Kelley, DS, Warren, JM, Simon, VA, et al. (2002) Similar effects of c9, t11-CLA and t10, c12-CLA on immune cell functions in mice. Lipids 37, 725728.
24Kang, JH, Lee, GS, Jeung, EB, et al. (2007) Trans-10, cis-12-conjugated linoleic acid increases phagocytosis of porcine peripheral blood polymorphonuclear cells in vitro. Br J Nutr 97, 117125.
25Son, SM, Kang, JH, Lee, GS, et al. (2006) Induction of interleukin-8 expression in porcine peripheral blood mononuclear cells by trans10-cis12 conjugated linoleic acid. Vet Immunol Immunopathol 112, 284289.
26Nakamura, YK & Omaye, ST (2009) 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 25, 800811.
27Chung, S, Brown, JM, Provo, JN, et al. (2005) Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. J Biol Chem 280, 3844538456.
28Loscher, CE, Draper, E, Leavy, O, et al. (2005) Conjugated linoleic acid suppresses NF-kappa B activation and IL-12 production in dendritic cells through ERK-mediated IL-10 induction. J Immunol 175, 49904998.
29Eskdale, J, Kube, D, Tesch, H, et al. (1997) Mapping of the human IL10 gene and further characterization of the 5′ flanking sequence. Immunogenetics 46, 120128.
30Moore, KW, de Waal Malefyt, R, Coffman, RL, et al. (2001) Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol 19, 683765.
31Hwang, DM, Kundu, JK, Shin, JW, et al. (2007) cis-9, trans-11-Conjugated linoleic acid down-regulates phorbol ester-induced NF-kappaB activation and subsequent COX-2 expression in hairless mouse skin by targeting IkappaB kinase and PI3K-Akt. Carcinogenesis 28, 363371.
32Zhao, L, Yin, J, Li, D, et al. (2005) 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 59, 429438.
33Cheng, WL, Lii, CK, Chen, HW, et al. (2004) Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway. J Agric Food Chem 52, 7178.
34Meadus, WJ, MacInnis, R, Dugan, ME, et al. (2002) Prolonged dietary treatment with conjugated linoleic acid stimulates porcine muscle peroxisome proliferator activated receptor gamma and glutamine-fructose aminotransferase gene expression in vivo. J Mol Endocrinol 28, 7986.
35Evans, M, Park, Y, Pariza, M, et al. (2001) trans-10, cis-12 Conjugated linoleic acid reduces triglyceride content while differentially affecting peroxisome proliferator activated receptor gamma2 and aP2 expression in 3T3-L1 preadipocytes. Lipids 36, 12231232.
36Alibin, CP, Kopilas, MA, Anderson, HD, et al. (2008) Suppression of cardiac myocyte hypertrophy by conjugated linoleic acid: role of peroxisome proliferator-activated receptors alpha and gamma. J Biol Chem 283, 1070710715.
37Nakatani, T, Tsuboyama-Kasaoka, N, Takahashi, M, et al. (2002) Mechanism for peroxisome proliferator-activated receptor-alpha activator-induced up-regulation of UCP2 mRNA in rodent hepatocytes. J Biol Chem 277, 95629569.
38Song, DH, Kang, JH, Lee, GS, et al. (2007) 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 37, 227235.
39Szatmari, I, Rajnavolgyi, E & Nagy, L (2006) PPARgamma, a lipid-activated transcription factor as a regulator of dendritic cell function. Ann N Y Acad Sci 1088, 207218.
40Marion-Letellier, R, Butler, M, Déchelotte, P, et al. (2008) Comparison of cytokine modulation by natural peroxisome proliferator-activated receptor gamma ligands with synthetic ligands in intestinal-like Caco-2 cells and human dendritic cells – potential for dietary modulation of peroxisome proliferator-activated receptor gamma in intestinal inflammation. Am J Clin Nutr 87, 939948.
41Ringseis, R, Gahler, S & Eder, K (2008) Conjugated linoleic acid isomers inhibit platelet-derived growth factor-induced NF-kappaB transactivation and collagen formation in human vascular smooth muscle cells. Eur J Nutr 47, 5967.
42Hontecillas, R, Wannemeulher, MJ, Zimmerman, DR, et al. (2002) Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid. J Nutr 132, 20192027.
43Bassaganya-Riera, J & Hontecillas, R (2006) CLA and n-3 PUFA differentially modulate clinical activity and colonic PPAR-responsive gene expression in a pig model of experimental IBD. Clin Nutr 25, 454465.
44Bassaganya-Riera, J, Reynolds, K, Martino-Catt, S, et al. (2004) Activation of PPARγ and δ by conjugated linoleic acid mediates protection from experimental inflammatory bowel disease. Gastroenterology 127, 777791.
45Evans, NP, Misyak, SA, Schmelz, EM, et al. (2010) Conjugated linoleic acid ameliorates inflammation-induced colorectal cancer in mice through activation of PPARγ. J Nutr 140, 515521.
46Jaudszus, A, Krokowski, M, Möckel, P, et al. (2008) cis-9, trans-11-Conjugated linoleic acid inhibits allergic sensitization and airway inflammation via a PPARgamma-related mechanism in mice. J Nutr 138, 13361342.
47Larsen, AE, Cameron-Smith, D & Crowe, TC (2008) Conjugated linoleic acid suppresses myogenic gene expression in a model of human muscle cell inflammation. J Nutr 138, 1216.
48Vereecke, L, Beyaert, R & van Loo, G (2009) The ubiquitin-editing enzyme A20 (TNFAIP3) in a central regulator of immunopathology. Trends Immunol 30, 383391.
49Coornaert, B, Carpentier, I & Beyaert, R (2009) A20: central gatekeeper in inflammation and immunity. J Biol Chem 284, 82178221.
50Hitotsumatsu, O, Ahmad, RC, Tavares, R, et al. (2008) The ubiquitin-editing enzyme A20 restricts nucleotide-binding oligomerization domain containing 2-triggered signals. Immunity 28, 381390.

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