한국식품영양과학회지 (Journal of the Korean Society of Food Science and Nutrition)

  • 제42권12호
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  • Pages.1930-1939
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  • 2013
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  • 1226-3311(pISSN)
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  • 2288-5978(eISSN)
한국식품영양과학회 (The Korean Society of Food Science and Nutrition)
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청국장이 난소적출 마우스의 면역 기능에 미치는 영향

Effects of Fermented Soybean Paste Chungkukjang on the Immunoreactivity in Ovariectomized Mice

  • 박현진 (숙명여자대학교 생활과학대학 식품영양학과) ;
  • 윤이나 (숙명여자대학교 대학원 생명시스템학과 식품생명시스템 전공) ;
  • 김현숙 (숙명여자대학교 생활과학대학 식품영양학과)
  • Park, Hyunjin (Div. of Food and Nutrition, College of Human Ecology, Sookmyung Women's University) ;
  • Yoon, Leena (Div. of Food and Nutritional Science & Life Systems, Sookmyung Women's University) ;
  • Kim, Hyun-Sook (Div. of Food and Nutrition, College of Human Ecology, Sookmyung Women's University)
  • 투고 : 2013.08.20
  • 심사 : 2013.11.11
  • 발행 : 2013.12.31
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초록

본 연구에서는 천연 식품으로부터 면역증진능을 갖는 식품 소재를 검색하기 위한 연구의 일환으로 골대사 약화 상태의 마우스에게 청국장 배합 사료를 투여했을 때 카제인 배합사료에 비하여 가질 수 있는 세포 매개성 면역능의 증강 효과를 규명하기 위한 목적으로 실시되었다. 제 1단계로서 난소적출군은 저칼슘 식이, Sham군은 AIN-76 식이를 6주간 공급한 후, 각 군을 청국장 배합 사료군 혹은 카제인 배합사료군으로 나누어 8주간 제 2단계의 식이를 공급하였다. 면역 지표로는 비장세포 증식능, 혈중 T 림프구 아형수와 혈중 사이토카인(IL-2, IL-4, IL-6, IL-10, IFN-${\gamma}$, TNF-${\alpha}$)의 분비량을 측정하였다. 그 결과 난소적출군에서 청국장배합 사료군의 비장 세포 증식능이 카제인 배합 사료군보다 유의적으로 높았으며, 혈중 T 림프구 아형 비율인 CD4/CD8의 비율도 청국장 배합 사료군에서 더 높았다. 혈중 사이토카인 분비량을 측정한 결과 난소적출군에서 청국장 배합 사료 투여군의 IL-6와 TNF-${\alpha}$ 분비량이 카제인 배합 사료 투여군에 비해 유의적으로 낮았다. 난소적출 마우스의 면역능에 청국장 배합 사료가 미치는 영향으로 카제인 배합사료에 비하여 비장 세포 증식능 활성화, 골 대사와 연관있는 대표적 사이토카인인 IL-6와 TNF-${\alpha}$ 분비 억제 및 조절 등을 들 수 있다. 뿐만 아니라, 체중 증가량을 조절하는 역할을 하는 것으로 관찰되었다. 따라서 청국장 배합 사료는 난소적출 마우스 면역계의 조절 기전에 작용하여 면역세포 활성을 촉진시키고 효과적으로 작용할 수 있으리라 사료된다. 이러한 연구 결과를 토대로 기능성 식품 개발에 기초연구 자료가 될 것으로 기대되며 향후 청국장의 면역 활성물질의 분리 및 동정을 위한 연구의 뒷받침이 될 수 있을 것으로 생각된다.

It has been reported that Chungkukjang, one of Korean traditional fermented soybean products, may improve hypertension, diabetes, and hyperlipidemia. In this study, we sought to investigate the immunoenhancing effects of Chungkukjang in ovariectomized mice. For the first period, female SLC ddy mice were either sham-operated (Sham; n=27) or ovariectomized (OVX; n=27). As a basal diet, ovariectomized mice were fed low-calcium diet for faster induction of osteoporosis for six weeks, and those in the Sham group were fed AIN-76 diet. For the second period, half of the OVX group (n=9) and the Sham group (n=9) were fed a Chungkukjang-based diet (CKJ); whereas the other half (OVX; n=9/ Sham; n=9) were fed a casein-based diet (CSI) for 8 weeks. After a second period, we collected the blood via heart puncture and measured the splenocytes proliferation, T lymphocyte subsets by flowcytometry, and levels of serum cytokines (IL-2, IL-4, IL-6, IL-10, IFN-${\gamma}$ and TNF-${\alpha}$) by ELISA assay. The OVX+CKJ group showed higher splenocytes proliferation, higher ratio of CD4/CD8, and lower levels of IL-6 and TNF-${\alpha}$ cytokines compared to the OVX+CSI group. The Sham+CKJ group showed cytokine productions, such as higher levels of IL-10 and IFN-${\gamma}$, and lower levels of IL-6 and TNF-${\alpha}$ compared to the Sham+CSI group. The result of this study suggests that Chungkukjang may lower the proinflammatory cytokine levels in both the OVX and Sham groups. In addition, Chungkukjang could make a balance of T cell subset proliferations and enhance the splenocyte proliferations in the OVX group.

키워드

참고문헌

  1. Lee BK, Jang YS, Yi SY, Chung KS, Choi SY. 1997. Immunomodulators extracted from Korean-style fermented soybean paste and their function. 1. Isolation of B cell mitogen from Korean-style fermented soybean paste. Korean J Immunol 19: 559-570.
  2. Adlercreutz H, Mazur W. 1997. Phyto-oestrogens and Western diseases. Ann Med 29: 95-120. https://doi.org/10.3109/07853899709113696
  3. Ko HS, Cho DH, Hwang SY, Kim YM. 1999. The effect of quality improvement by Chungkuk-jang's processing methods. Korean J Food & Nutr 12: 1-6.
  4. Youn KC, Kim DH, Kim JO, Park BJ, Yook HS, Cho JM, Byun MW. 2002. Quality characteristics of the chungkookjang fermented by the mixed culture of Bacillus natto and B. licheniformis. J Korean Soc Food Sci Nutr 31: 204-210. https://doi.org/10.3746/jkfn.2002.31.2.204
  5. Kim J, Yoo S, Choe J, Park HJ, Hong S, Chang C. 1998. Physicochemical properties of traditional Chonggugjang produced in different regions. Agric Chem Biotechnol 41: 377-383.
  6. Joo EY, Park CS. 2011. Antioxidant and fibrinolytic activities of extracts from soybean and Chungkukjang (fermented soybean paste). Korean J Food Preserv 18: 930-937. https://doi.org/10.11002/kjfp.2011.18.6.930
  7. Lee KH, Rye SH, Lee YS, Kim YM, Moon GS. 2005. Changes of antioxidative activity and related compounds on the Chungkukjang preparation by adding drained boiling water. Korean J Food Cookery Sci 21: 163-170.
  8. Choi YB, Sohn HS. 1998. Isoflavone content in Korean fermented and unfermented soybean foods. Korean J Food Sci Technol 30: 745-750.
  9. Chung WY, Kim SK, Son JY. 2008. Isoflavones contents and physiological activities of soybeans fermented with Aspergillus oryzae or Bacillus natto. J Korean Soc Food Sci Nutr 37: 141-147. https://doi.org/10.3746/jkfn.2008.37.2.141
  10. Alekel DL, Germain AS, Peterson CT, Hanson KB, Stewart JW, Toda T. 2000. Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women. Am J Clin Nutr 72: 844-852. https://doi.org/10.1093/ajcn/72.3.844
  11. Tsuchida K, Mizushima S, Toba M, Soda K. 1999. Dietary soybeans intake and bone mineral density among 995 middle-aged women in Yokohama. J Epidemiol 9: 14-19.
  12. Potter SM, Baum JA, Teng H, Stillman RJ, Shay NF, Erdman JW Jr. 1998. Soy protein and isoflavones: their effects on blood lipids and bone density in postmenopausal women. Am J Clin Nutr 68: 1375S-1379S. https://doi.org/10.1093/ajcn/68.6.1375S
  13. Masilamani M, Wei J, Sampson HA. 2012. Regulation of the immune response by soybean isoflavones. Immunol Res 54: 95-110. https://doi.org/10.1007/s12026-012-8331-5
  14. Baeza I, De Castro NM, Arranz L, De la Fuente M. 2010. Soybean and green tea polyphenols improve immune function and redox status in very old ovariectomized mice. Rejuvenation Res 13: 665-674 https://doi.org/10.1089/rej.2010.1049
  15. Kim JI, Kang MJ, Kwon TW. 2003. Antidiabetic effect of soybean and Chongkukjang. Korea Soybean Digest 20: 44-52.
  16. Makino T, Ono T, Muso E, Honda G. 1998. Inhibitory effect of Perilla frutescens and its phenolic constituents on cultured murine mesangial cell proliferation. Planta Med 64: 541-545. https://doi.org/10.1055/s-2006-957510
  17. Coligan EJ, Kruisbeek MA, Margulies HD, Shevach ME, Strober W. 1993. Current protocols in immunology. Wiley Interscience, New York, NY, USA. p 532-534.
  18. Kurachi H, Adachi H, Ohtsuka S, Morishige K, Amemiya K, Keno Y, Shimomura I, Tokunaga K, Miyake A, Matsuzawa Y. 1993. Involvement of epidermal growth factor in inducing obesity in ovariectomized mice. Am J Physiol 265: E323-E231.
  19. Bray GA. 1992. Genetic, hypothalamic and endocrine features of clinical and experimental obesity. Prog Brain Res 93: 333-340. https://doi.org/10.1016/S0079-6123(08)64583-5
  20. Lorden JF, Caudle A. 1986. Behavioral and endocrinological effects of single injections of monosodium glutamate in the mouse. Neurobehav Toxicol Teratol 8: 509-519.
  21. Wegorzewska IN, Walters K, Weiser MJ, Cruthirds DF, Ewell E, Larco DO, Handa RJ, Wu TJ. 2008. Postovariectomy weight gain in female rats is reversed by estrogen receptor ${\alpha}$ agonist, propylpyrazoletriol. Am J Obstet Gynecol 199: e1-e5. https://doi.org/10.1016/j.ajog.2008.03.040
  22. Lee DJ, Kim SM. 2001. Correlation of the bone mineral density and weight reduction therapy in estrogen replaced obese postmenopausal women. Korean J Obes 10: 306-313.
  23. Turcato E, Zamboni M, De Pergola G, Armellini F, Zivelonghi A, Bergamo-Andreis IA, Giorgino R, Bosello O. 1997. Interrelationships between weight loss, body fat distribution and sex hormones in pre- and postmenopausal obese women. J Intern Med 241: 363-372. https://doi.org/10.1046/j.1365-2796.1997.120129000.x
  24. Haffner SM, Katz MS, Dunn JF. 1991. Increased upper body and overall adiposity is associated with decreased sex hormone binding globulin in postmenopausal women. Int J Obes 15: 471-478.
  25. Lee MR, Park MN, Mun JY, Lee YS. 2011. Effects of a low calcium diet and oxalate intake on calcium deposits in soft tissues and bone metabolism in ovariectomized rats. Korean J Nutr 44: 101-111. https://doi.org/10.4163/kjn.2011.44.2.101
  26. Effros RB. 2004. Replicative senescence of CD8 T cells: effect on human ageing. Exp Gerontol 39: 517-524. https://doi.org/10.1016/j.exger.2003.09.024
  27. Arron JR, Choi Y. 2000. Bone versus immune system. Nature 408: 535-536. https://doi.org/10.1038/35046196
  28. Roggia C, Gao Y, Cenci S, Weitzmann MN, Toraldo G, Isaia G, Pacifici R. 2001. Up-regulation of TNF-producing T cells in the bone marrow: a key mechanism by which estrogen deficiency induces bone loss in vivo. Proc Natl Acad Sci U S A 98: 13960-13965. https://doi.org/10.1073/pnas.251534698
  29. Weitzmann MN, Cenci S, Rifas L, Brown C, Pacifici R. 2000. Interleukin-7 stimulates osteoclast formation by upregulating the T-cell production of soluble osteoclastogenic cytokines. Blood 96: 1873-1878.
  30. Buchinsky FJ, Ma Y, Mann GN, Rucinski B, Bryer HP, Romero DF, Jee WS, Epstein S. 1996. T lymphocytes play a critical role in the development of cyclosporin A-induced osteopenia. Endocrinology 137: 2278-2285. https://doi.org/10.1210/endo.137.6.8641176
  31. John V, Hock JM, Short LL, Glasebrook AL, Galvin RJ. 1996. A role for CD8+ T lymphocytes in osteoclast differentiation in vitro. Endocrinology 137: 2457-2463. https://doi.org/10.1210/endo.137.6.8641199
  32. Pietschmann P, Grisar J, Thien R, Willheim M, Kerschan- Schindl K, Preisinger E, Peterlik M. 2001. Immune phenotype and intracellular cytokine production of peripheral blood mononuclear cells from postmenopausal patients with osteoporotic fractures. Exp Gerontol 36: 1749-1759. https://doi.org/10.1016/S0531-5565(01)00125-5
  33. Teitelbaum SL. 2004. Postmenopausal osteoporosis, T cells, and immune dysfunction. Proc Natl Acad Sci U S A 101: 16711-16712. https://doi.org/10.1073/pnas.0407335101
  34. Jilka RL. 1998. Cytokines, bone remodeling, and estrogen deficiency: a 1998 update. Bone 23: 75-81. https://doi.org/10.1016/S8756-3282(98)00077-5
  35. Pacifici R. 1998. Cytokines, estrogen, and postmenopausal osteoporosis－the second decade. Endocrinology 139: 2659-2661. https://doi.org/10.1210/endo.139.6.6087
  36. Manolagas SC. 1995. Role of cytokines in bone resorption. Bone 17: 63S-67S. https://doi.org/10.1016/8756-3282(95)00135-Z
  37. Manolagas SC. 2000. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr Rev 21: 115-137.
  38. McCormick RK. 2007. Osteoporosis: integrating biomarkers and other diagnostic correlates into the management of bone fragility. Altern Med Rev 12: 113-145.
  39. Zou W, Amcheslavsky A, Takeshita S, Drissi H, Bar-Shavit Z. 2005. TNF-${\alpha}$ expression is transcriptionally regulated by RANK ligand. J Cell Physiol 202: 371-378. https://doi.org/10.1002/jcp.20127
  40. Kudo O, Fujikawa Y, Itonaga I, Sabokbar A, Torisu T, Athanasou NA. 2002. Proinflammatory cytokine (TNF${\alpha}$/ IL-1${\alpha}$) induction of human osteoclast formation. J Pathol 198: 220-227. https://doi.org/10.1002/path.1190
  41. Komine M, Kukita A, Kukita T, Ogata Y, Hotokebuchi T, Kohashi O. 2001. Tumor necrosis factor-${\alpha}$ cooperates with receptor activator of nuclear factor κB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture. Bone 28: 474-483. https://doi.org/10.1016/S8756-3282(01)00420-3
  42. Pacifici R. 1996. Estrogen, cytokines, and pathogenesis of postmenopausal osteoporosis. J Bone Miner Res 11: 1043-1051.
  43. Manolagas SC, Jilka RL. 1995. Bone marrow, cytokines, and bone remodeling. Emerging insights into the pathophysiology of osteoporosis. N Engl J Med 332: 305-311. https://doi.org/10.1056/NEJM199502023320506
  44. Brubaker JO, Thompson CM, Morrison LA, Knipe DM, Siber GR, Finberg RW. 1996. Th1-associated immune responses to beta-galactosidase expressed by a replication-defective herpes simplex virus. J Immunol 157: 1598-1604.
  45. Snapper CM, Paul WE. 1987. B cell stimulatory factor-1 (interleukin 4) prepares resting murine B cells to secrete IgG1 upon subsequent stimulation with bacterial lipopolysaccharide. J Immunol 139: 10-17.
  46. Sugiyama E, Taki H, Kuroda A, Mino T, Yamashita N, Kobayashi M. 1996. Interleukin-4 inhibits prostaglandin E2 production by freshly prepared adherent rheumatoid synovial cells via inhibition of biosynthesis and gene expression of cyclo-oxygenase II but not of cyclo-oxygenase I. Ann Rheum Dis 55: 375-382. https://doi.org/10.1136/ard.55.6.375
  47. Suzuki H, Sugiyama E, Tunru IS, Yamashita N, Matsuno H, Hamazaki T, Kobayashi M. 1993. Suppressive effect of interleukin-4 (IL-4) on IL-6 production by adherent rheumatoid synovial cells. Clin Immunol Immunopathol 66: 67-72. https://doi.org/10.1006/clin.1993.1009
  48. Hart PH, Cooper RL, Finlay-Jones JJ. 1991. IL-4 suppresses IL-1 beta, TNF-alpha and PGE2 production by human peritoneal macrophages. Immunology 72: 344-349.
  49. te Velde AA, Huijbens RJ, Heije K, de Vries JE, Figdor CG. 1990. Interleukin-4 (IL-4) inhibits secretion of IL-1 beta, tumor necrosis factor alpha, and IL-6 by human monocytes. Blood 76: 1392-1397.
  50. Miossec P, Chomarat P, Dechanet J, Moreau JF, Roux JP, Delmas P, Banchereau J. 1994. Interleukin-4 inhibits bone resorption through an effect on osteoclasts and proinflammatory cytokines in an ex vivo model of bone resorption in rheumatoid arthritis. Arthritis Rheum 37: 1715-1722. https://doi.org/10.1002/art.1780371202
  51. Riancho JA, Zarrabeitia MT, Gonzalez-Macias J. 1993. Interleukin-4 modulates osteoclast differentiation and inhibits the formation of resorption pits in mouse osteoclast cultures. Biochem Biophys Res Commun 196: 678-685. https://doi.org/10.1006/bbrc.1993.2303
  52. Joosten LA, Lubberts E, Helsen MM, Saxne T, Coenen-de Roo CJ, Heinegård D, van den Berg WB. 1999. Protection against cartilage and bone destruction by systemic interleukin-4 treatment in established murine type II collagen-induced arthritis. Arthritis Res 1: 81-91. https://doi.org/10.1186/ar14
  53. Lewis DB, Liggitt HD, Effmann EL, Motley ST, Teitelbaum SL, Jepsen KJ, Goldstein SA, Bonadio J, Carpenter J, Perlmutter RM. 1993. Osteoporosis induced in mice by overproduction of interleukin 4. Proc Natl Acad Sci U S A 90: 11618-11622. https://doi.org/10.1073/pnas.90.24.11618
  54. Takayanagi H, Ogasawara K, Hida S, Chiba T, Murata S, Sato K, Takaoka A, Yokochi T, Oda H, Tanaka K, Nakamura K, Taniguchi T. 2000. T-cell-mediated regulation of osteoclastogenesis by signalling cross-talk between RANKL and IFN-${\gamma}$. Nature 408: 600-605. https://doi.org/10.1038/35046102

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