한국임상수의학회지 (Journal of Veterinary Clinics)

  • 제28권2호
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  • Pages.190-195
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  • 2011
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  • 1598-298X(pISSN)
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  • 2384-0749(eISSN)
한국임상수의학회 (The Korean Society of Veterinary Clinics)
권호 표지

돼지 말초혈액 단핵구세포에서 trans-10, cis-12 conjugated linoleic acid의 TNF-${\alpha}$ 생산에 대한 nuclear factor-${\kappa}B$ p65 활성 조절 효과

Trans-10, cis-12 Conjugated Linoleic Acid Modulates Nuclear Factor-${\kappa}B$ p65 Activity on the Production of Tumor Necrosis Factor-${\alpha}$ in Porcine Peripheral Blood Mononuclear Cells

  • 김영범 (충북대학교 수의과대학 수의내과학 교실) ;
  • 이일우 (충북대학교 수의과대학 수의내과학 교실) ;
  • 강지훈 (충북대학교 수의과대학 수의내과학 교실) ;
  • 양만표 (충북대학교 수의과대학 수의내과학 교실)
  • Kim, Young-Beum (Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University) ;
  • Lee, Ill-Woo (Laboratory of Veterinary Internal Medicine, 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, Mban-Pyo (Laboratory of Veterinary Internal Medicine, Department of Veterinary Medicine, College of Veterinary Medicine, Chungbuk National University)
  • 심사 : 2011.04.14
  • 발행 : 2011.04.30
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초록

본 연구에서 돼지 PBMC에 t10c12-CLA 처리는 TNF-${\alpha}$생산을 증가시켰으나, LPS 자극 PBMC에서는 TNF-${\alpha}$생산을 감소시켰다. t10c12-CLA 처리는 PBMC의 inhibitory ${\kappa}B$ ($I{\kappa}B$)-${\alpha}$ 단백질 분해를 증가시키고 NF-${\kappa}B$ p65 활성 수준을 증가시켰다. 그러나 LPS 자극 PBMC에서는 상반되는 효과가 관찰되었다. 특히, LPS 비자극 PBMC에서 t10c12-CLA는 NF-${\kappa}B$ 저해제인 caffeic acid phenethyl ester (CAPE)를 처리한 경우 NF-${\kappa}B$ p65 활성 수준을 증가시켰으나 반대로 LPS로 자극한 CAPE 처리 PBMC에서는 NF-${\kappa}B$ p65 활성 수준을 억제시켰다. 이상의 결과는 t10c12-CLA가 돼지 PBMC에 있어 LPS 자극 유무에 따라 다른 효과를 가질 수 있으며, 이는 NF-${\kappa}B$ p65 활성도의 변화와 관련성이 있음을 보여주고 있다.

Nuclear factor ${\kappa}B$ (NF-${\kappa}B$) is a nuclear transcription factor that modulates the expression of inflammatory cytokines such as tumor necrosis factor (TNF)-${\alpha}$. trans-10, cis-12 (t10c12)-conjugated linoleic acid (CLA) participates in the inhibition of TNF-${\alpha}$ production upon lipopolysaccharide (LPS)-stimulation. However, in our previous study, t10c12-CLA enhanced the production of TNF-${\alpha}$ by LPS-unstimulated porcine peripheral blood mononuclear cells (PBMCs) and RAW 264.7 macrophages in vitro. To resolve this apparent contradiction, we hypothesized that the effect of t10c12-CLA on TNF-${\alpha}$ production depends on NF-${\kappa}B$ activation induced by LPS stimulation. To test this hypothesis, we assessed the in vitro effect of t10c12-CLA on TNF-${\alpha}$ production and NF-${\kappa}B$ p65 activity in LPS-stimulated and LPS-unstimulated porcine PBMCs. t10c12-CLA treatment resulted in increased TNF-${\alpha}$ production by LPS-unstimulated PBMCs but decreased TNF-${\alpha}$ production by LPS-stimulated PBMCs. t10c12-CLA increased the degradation of inhibitory ${\kappa}B$ ($I{\kappa}B$)-${\alpha}$ protein and activated NF-${\kappa}B$ p65 in LPS-unstimulated PBMCs, but had the opposite effect in LPS-stimulated PBMCs. Notably, t10c12-CLA enhanced NF-${\kappa}B$ p65 binding activity in LPS-unstimulated PBMCs exposed to caffeic acid phenethyl ester (CAPE), a NF-${\kappa}B$ inhibitor. Conversely, it inhibited NF-${\kappa}B$ p65 binding activity in LPS-stimulated PBMCs exposed to CAPE. These results suggest that t10c12-CLA may have different actions under different physiological conditions, and that its effect may be associated with a change in NF-${\kappa}B$ p65 activity.

키워드

참고문헌

  1. Banni S. Conjugated Iinoleic acid metabolism. Curr Opin Lipidol 2002; 13: 261-266. https://doi.org/10.1097/00041433-200206000-00005
  2. Bassaganya-Riera J, Hontecillas R, Beitz DC. Colonic antiinflammatory mechanisms of conjugated linoleic acid. Clin Nutr 2002; 21: 451-459. https://doi.org/10.1054/clnu.2002.0594
  3. Belury MA. Inhibition of carcinogenesis by conjugated linoleic acid: potential mechanisms of action. J Nutr 2002; 132: 2995-2998.
  4. Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G. Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem 2006; 17: 789-810. https://doi.org/10.1016/j.jnutbio.2006.02.009
  5. Bradley JR. TNF-mediated inflammatory disease. J Pathol 2008; 214: 149-160. https://doi.org/10.1002/path.2287
  6. Brown JM, Boysen MS, Chnng S, Fabiyi O, Morrison RF, Mandrup S, McIntosh MK. Conjugated linoleic acid induces human adipocyte delipidation: autocrine/paracrine regulation of MEK/ERK signaling by adipocytokines. J Biol Chem 2004; 279: 26735-26747. https://doi.org/10.1074/jbc.M401766200
  7. 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.
  8. Cheng WL, Lii CK, Chen HW, Lin TH, Liu KL. Contribution of conjugated linoleic acid to the suppression of inflammatory responses through the regulation of the NF-kappaB pathway. J Agric Food Chem 2004; 52: 71-78. https://doi.org/10.1021/jf0348626
  9. Chin SF, Storkson JM, Liu W, Albright KJ, Pariza MW. Conjugated linoleic acid (9,11- and 10,12-octadecadienoic acid) is produced in conventional but not germ-free rats fed linoleic acid. J Nutr 1994; 124: 694-701.
  10. Chung S, Brown JM, Provo JN, Hopkins R, McIntosh MK. Conjugated linoleic acid promotes human adipocyte insulin resistance through NFkappaB-dependent cytokine production. J Biol Chem 2005; 280: 38445-38456. https://doi.org/10.1074/jbc.M508159200
  11. Cook ME, Miller CC, Park Y, Pariza M. Immune modulation by altered nutrient metabolism: nutritional control of immune-induced growth depression. Poult Sci 1993; 72: 1301-1305. https://doi.org/10.3382/ps.0721301
  12. Ghosh S, Hayden MS. New regulators of NF-kappaB in inflammation. Nat Rev Immunol 2008; 8: 837-848. https://doi.org/10.1038/nri2423
  13. Hwang DM, Kundu JK, Shin JW, Lee JC, Lee HJ, Surh YJ. 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 P13K-Akt. Carcinogenesis 2007; 28: 363-371.
  14. Kang JH, Lee GS, Jeung EB, Yang MP. Trans-10, cis-12-conjugated linoleic acid increases phagocytosis of porcine peripheral blood polymorphonuclear cells in vitro. Br J Nutr 2007; 97: 117-125. https://doi.org/10.1017/S0007114507280584
  15. Kelley DS, Warren JM, Simon VA, Bartolini G, Mackey BE, Erickson KL. Similar effects of c9, t11-CLA and t10,c12-CLA on immune cell functions in mice, Lipids 2002; 37: 725-728. https://doi.org/10.1007/s11745-002-0954-7
  16. Lee KN, Kritchevsky D, Pariza MW. Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 1994; 108: 19-25. https://doi.org/10.1016/0021-9150(94)90034-5
  17. Li G, Dong B, Butz DE, Park Y, Pariza MW, Cook ME. NFkappaB independent inhibition of lipopolysaccharide-induced cyclooxygenase by a conjugated linoleic acid cognate, conjugated nonadecadienoic acid. Biochim Biophys Acta 2006; 1761: 969-972. https://doi.org/10.1016/j.bbalip.2006.07.014
  18. Loscher CE, Draper E, Leavy O, Kelleher D, Mills KH, Rochc HM. Conjugated linoleic acid suppresses NF-kappa B activation and IL-12 production in dendritic cells through ERK-mediated IL- 10 induction. J ImmunoI 2005; 175: 4990-4998.
  19. MiIler CC, Park Y, Pariza MW, Cook ME. Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection. Biochem Biophys Res Commun 1994; 198: 1107-1112. https://doi.org/10.1006/bbrc.1994.1157
  20. Natarajan K, Singh S, Burke TR, Jr., Grunberger D, Aggarwal BB. Caffeic acid phenethyl ester is a potent and specific inhibitor of activation of nuclear transcription factor NF-kappa B. Proc Natl Acad Sci U S A 1996; 93: 9090-9095. https://doi.org/10.1073/pnas.93.17.9090
  21. Pariza MW, Park Y, Cook ME. Mechanisms of action of conjugated linoleic acid: evidence and speculation. Proc Soc Exp Biol Med 2000; 223: 8-13. https://doi.org/10.1046/j.1525-1373.2000.22302.x
  22. Pariza MW, Park Y, Cook ME. The biologically active isomers of conjugated linoleic acid. Prog Lipid Res 2001; 40: 283-298 https://doi.org/10.1016/S0163-7827(01)00008-X
  23. Parodi PW. Cows' milk fat components as potential anticarcinogenic agents. J Nutr 1997; 127: 1055-1060.
  24. Poirier H, Shapiro JS, Kim RJ, Lazar MA. Nutritional supplementation with trans-10, cis-12-conjugated linoleic acid induces inflammation of white adipose tissue. Diabetes 2006; 55: 1634-1641. https://doi.org/10.2337/db06-0036
  25. Salas-Salvado J, Marquez-Sandoval F, Bullo M. Conjugated linoleic acid intake in humans: a systematic review focusing on its effect on body composition, glucose, and lipid metabolism. Crit Rev Food Sci Nutr 2006; 46: 479-488. https://doi.org/10.1080/10408390600723953
  26. 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. https://doi.org/10.1016/j.cyto.2007.04.003
  27. Storey A, Rogers JS, McArdle F, Jackson MJ, Rhodes LE. Conjugated linoleic acids modulate UVR-induced IL-8 and PGE2 in human skin cells: potential of CLA isomers in nutritional photoprotection. Carcinogenesis 2007; 28: 1329-1333. https://doi.org/10.1093/carcin/bgm065
  28. Tanaka H, Fujita N, Tsuruo T. 3-Phosphoinositide-dependent protein kinase-I-mediated IkappaB kinase beta (IkkB) phosphorylation activates NF-kappaB signaling. J Biol Chem 2005; 280: 40965-40973. https://doi.org/10.1074/jbc.M506235200
  29. Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O. Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 2000; 49: 1534-1542. https://doi.org/10.2337/diabetes.49.9.1534
  30. Watkins BA, Li Y, Lippman HE, Reinwald S, Seifert MF. A test of Ockham's razor: implications of conjugated linoleic acid in bone biology. Am J Clin Nutr 2004; 79: 1175S-1185S.
  31. 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 https://doi.org/10.1016/S1388-1981(02)00126-9
  32. 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. https://doi.org/10.1080/17450390500353333