DOI QR코드

DOI QR Code

Immunoregulatory Effects of Saengshik on DSS-Induced Inflammatory Bowel Disease in Mouse Model System

DSS로 유도된 염증성 장 질환 마우스 동물모델에서 생식이 장관 임파조직내 면역조절 기능에 미치는 영향

  • Lim, Beong-Ou (Dept. of Life Science, College of Biomedical & Health Science, Konkuk University) ;
  • Jeong, Yong-Jun (Dept. of Life Science, College of Biomedical & Health Science, Konkuk University) ;
  • Park, Mi-Hyoun (The Erom R&D Center) ;
  • Kim, Jong-Dai (College of Biotechnology, Kangwon National University) ;
  • Hwang, Sung-Joo (The Erom R&D Center) ;
  • Yu, Byung-Pal (Dept. of Physiology, University of Texas Health Science Center)
  • 임병우 (건국대학교 의료생명대학 생명과학부) ;
  • 정용준 (건국대학교 의료생명대학 생명과학부) ;
  • 박미현 ((주)이롬 생명과학연구원) ;
  • 김종대 (강원대학교 BT 특성화학부 대학) ;
  • 황성주 ((주)이롬 생명과학연구원) ;
  • 유병팔 (미국 텍사스주립대학 건강과학센터)
  • Published : 2007.01.31

Abstract

This study was conducted on the immunoregulatory effect of Saengshik on gut-associated lymphoid tissue with inflammatory bowel disease. Although the contents of IgA increased in mesenteric lymph node, IgE content was suppressed by Saengshik. The same results were found in spleen, but IgA and IgE responses were very weak. Concentration of fecal IgA was high from the first day through the third day in Saengshik group. In DSS + Saengshik group, concentration of IgA was high till the 2nd day and it maintained the highest level among the test groups on 5th day. Concentration of IFN-gamma and IL-2 was the highest in the Saengshik group, but the concentration of TNF-alpha was lower in DSS + Saengshik compared to DSS. The expressions of STAT1 in Saengshik group were high, while those of STAT6 were low According to these findings, Saengshik exhibited effectiveness via increasing the IgA production, suppressing the IgE production, followed by inhibiting the production of IL-4 and IL-10. Saengshik also strengthened the immune system and alleviated injury in DSS -induced inflammation.

본 연구의 목적은 DSS로 유발시킨 대장염 동물모델에서 생식섭취가 장관 내 면역조절에 미치는 영향에 대하여 검토해보고자 했다. 그 결과, 생식섭취가 DSS로 유발시킨 대장염에서 normal군보다 IFN-$\gamma$의 함량을 증가시키고, IL-4와 IL-10의 함량은 감소시킴이 관찰되었다. 또한, 증가된 Th1 세포의 cytokine과 감소된 Th2 세포의 cytokine은 염증이 유발된 후, 생식을 통한 치료로써 변환시킬 수 있음을 증명하였다. 이러한 연구 결과를 볼 때 DSS로 유발시킨 대장염에서 생식 섭취를 통한 치료는 IL-4와 IL-10과 같은 염증성 cytokine의 억제기능을 통하여 면역시스템을 강화시키고, 손상된 염증을 완화시켜 줄 것으로 판단된다. 생식의 면역조절에 관한 자세한 기전은 아직 밝혀져 있지 않지만, 염증성 장질환에서 생식섭취가 면역학적 역할에 대한 새로운 양상들에 대한 연구가 더욱더 필요할 것으로 사료된다.

Keywords

References

  1. Shoda R, Matsueda K, Yamato S, Umeda N. 1996. Epidemiologic analysis of Crohn's disease in Japan; increased dietary intake of n-6 poluunsaturated fatty acids and animal protein relates to the increased incidence of Crohn's disease in Japan. Am J Clin Nutr 63: 741-745 https://doi.org/10.1093/ajcn/63.5.741
  2. Song MK, Hong SG, Hwang SJ, Park OJ, Park MH. 2003. Improve effects of Saengshik on patients with fatty liver and hyperlipidemia in murine. Korean J Nutr 36: 834-840
  3. Lim BO, Yamada K, Nonaka M, Kuramoto Y, Hung P, Sugano M. 1997. Ditary fibers modulate indices of intestinal immune function in rats. J Nutr 127: 663-667 https://doi.org/10.1093/jn/127.5.663
  4. Lim BO, Choue RW, Park DK, Kim HC, Kim SY, Yamada K, Sugano M. 2002. Effect of dietary level of pectin on immunoglobulin and cytokine production by mesenteric lymph node lymphocytes and interleukin-2 receptor in rats. Food Sci Technol Res 8: 14-16 https://doi.org/10.3136/fstr.8.14
  5. Lim BO, Jolly CA, Zaman K, Fernandes G. 2000. Dietary (n-6) and (n-3) fatty acids and energy restirction modulate mesenteric lymph node lymphocytes function in autoimmune-prone (NZBxNZW)F1 mice. J Nutr 130: 1657- 1664
  6. Lim BO. 2001. Effect of ganhuangenin obtained from Scutellaria radix on the chemical mediator production of peritoneal exudate cells and immunoglobulin E level of mesenteric lymhp node lymphocytes in sprague-dawley rats. Phytotheraphy Res 16: 166-170 https://doi.org/10.1002/ptr.1034
  7. Yamada K, Hung P, Yoshimura K, Taniguchi S, Lim BO, Sugano M. 1996. Effect of unsaturated fatty acids and antioxidants on immunoglobulin production of rat mesenteric lymphnode lymphocytes of sprague-dawley rats. J Biochem 120: 138-144 https://doi.org/10.1093/oxfordjournals.jbchem.a021375
  8. Hung P, Yamada K, Lim BO, Mori M, Yuki T, Sugano M. 1997. Effect of unsaturated fatty acids and alpha-tocopherol on immunoglobulin levels in culture medium of rat mesenteric lymph node and spleen lymphocytes. J Biochem 121: 1054-1060 https://doi.org/10.1093/oxfordjournals.jbchem.a021694
  9. Kiyono H, Bienenstock J, McGhee JR, Ernst PB. 1992. The mucosal immune system: features of inductive and effector sites to consider in mucosal immunization and vaccine development. Reg Immunol 4: 54-62
  10. McGhee JR, Kiyono H. 1999. The mucosal immune system. In Fiundamental Immunology. 4th ed. Paul WE, ed. Lippincott-Raven Publishers, New York. p 909
  11. Kwon KH, Murakami A, Hayashi R, Ohigashi H. 2005. Interleukin-1beta targets interleukin-6 in progressing dextran sulfate sodium-induced experimental colitis. Biochem Biophys Res Commun 337: 647-654 https://doi.org/10.1016/j.bbrc.2005.09.107
  12. Cranston D, McWhinnie D, Collin J. 1988. Dietary fibre and gastrointestinal disease. Br J Surg 75: 508-512 https://doi.org/10.1002/bjs.1800750604
  13. Stephen AM, Cummings JH. 1980. Mechanism od action of dietary fibre in the human colon. Nature 284: 283-284 https://doi.org/10.1038/284283a0
  14. Stephen AM, Cummings JH. 1979. Water-holding by dietary fibre in vitro and its relationship to faecal output in man. Gut 20: 722-729 https://doi.org/10.1136/gut.20.8.722
  15. Burkitt DP, Walker AR, Painter NS. 1972. Effect of dietary fiber on stools and transit-times, and its role in the causation of disease. Lancet 300: 1408-1412 https://doi.org/10.1016/S0140-6736(72)92974-1
  16. Connel AM. 1976. Natural fiber and bowel dysfunction. Am J Clin Nutr 29: 1427-1431 https://doi.org/10.1093/ajcn/29.12.1427
  17. Cummings JH, Hill MJ, Jenkins DJ, Pearson JR, Wiggins HS. 1976. Change in fecal composition and colonic function due to cereal fiber. Am J Clin Nutr 29: 1468-1473 https://doi.org/10.1093/ajcn/29.12.1468
  18. Hallert C, Kaldma M, Petersson BG. 1991. Ispaghula husk may relieve gastrointestinal symptoms in ulcerative colitis in remission. Scand J Gastroenterology 26: 747-750 https://doi.org/10.3109/00365529108998594
  19. Blumberg RS. 1990. Relapse of chronic inflammatory bowel disease. Gastroenterology 98: 792-796 https://doi.org/10.1016/0016-5085(90)90305-K
  20. Leo S, Leandro G, Di Matteo G, Caruso ML, Lorusso D. 1989. Ulcerative colitis in remession is it possible to predict the risk of relapse? Digestion 44: 217-221 https://doi.org/10.1159/000199914
  21. Kang SM, Shim JY, Hwang SJ, Hong SG, Jang HE, Park MH. 2003. Effect of Saengsik supplementation on health impromvement in diet-induced hypercholesterolemic rats. J Korean Soc Food Sci Nutr 32: 906-912 https://doi.org/10.3746/jkfn.2003.32.6.906
  22. Sugano M, Kamo F, Ikeda I, Morioka H. 1976. Lipid-lowering activity of phytostanols in rats. Atherosclerosis 24: 301-309 https://doi.org/10.1016/0021-9150(76)90085-X
  23. Sandberg AS, Andersson H, Hallgren B, Hasselblad K, Isaksson B, Hulten L. 1981. Experimental model for in vivo determination of dietary fibre and its effect on the absorption of nutrients in the small intestine. Br J Nutr 45: 283-294 https://doi.org/10.1079/BJN19810105
  24. American Institute of Nutrition. 1977. Report of the American Institute of Nutrition ad hoc Committee on Standards for Nutrition Studies. J Nutr 107: 1340-1348 https://doi.org/10.1093/jn/107.7.1340
  25. Lim BO, Yamada K, Yoshimura K, Watanabe T, Pham H, Taniguchi S, Sugano M. 1995. Free bile acids inhibit IgE production by mouse spleen lymphocytes stimulated by lipopolysaccharide and interleukins. Biosci Biotech Biochem 59: 624-627 https://doi.org/10.1271/bbb.59.624
  26. Suk K, Kim SY, Kim H. 2002. Essential role of caspase-11 in activation-induced cell death of rat astrocytes. J Neurochem 80: 230-238 https://doi.org/10.1046/j.0022-3042.2001.00705.x
  27. Fukushima C, Matsuse H, Saeki S, Kawano T, Machida I, Kondo Y, Kohno S. 2005. Salivary IgA and oral candidiasis in asthmatic patients treated with inhaled corticosteroid. J Asthma 42: 601-604 https://doi.org/10.1080/02770900500216259
  28. Duncan DB. 1955. Multiple range and multiple F test. Biometrics 11: 1-42 https://doi.org/10.2307/3001478
  29. Finegold SM, Flora DJ, Atterbery HR, Sutter VL. 1974. Effects of diet on human fecal flora: comparison of Japanese and American diets. Am J Clin Nutr 27: 1456-1469 https://doi.org/10.1093/ajcn/27.12.1456
  30. Rao AV. 1995. Effects of dietary fiber on intestinal microflora and health. In Dietary fiber in Health & Disease. Kritchevsky D, Bonefield C, eds. Egan Press, St. Paul, MN. p 257-266
  31. Tappenden KA, Pratt VC, Goruk SD, Field CJ, McBurney MC. 1995. Short chain fatty fatty acid (SCFA) supplementation of total parenteral nutrition (TPN) improves whole body response to intestinal resection. FASEB J 9: 862A
  32. Lin CC, Shieh DE. 1996. The anti-inflammatory activity of Scutellaria rivularis extracts and its active components, baicalin, baicalein and wogonin. Am J Chin Med 24: 31-36 https://doi.org/10.1142/S0192415X96000050
  33. Kojouharoff G, Hans W, Obermeier F, Mannel DN, Andus T, Scholmerich J, Gross V, Falk W. 1997. Neutralization of tumor necrosis factor (TNF) but not of IL-1 reduce inflammation in chronic dextran sulfate sodium-induced colitis in mice. Clin Exp Immunol 107: 353-358 https://doi.org/10.1111/j.1365-2249.1997.291-ce1184.x
  34. Obermeier F, Kojouharoff G, Han W, Scholmerich J, Gross V, Falk W. 1999. Interferon-gamma (IFN-${\gamma}$) and tumor necrosis factor (TNF)-induced nitric oxide as toxic effector molecule in chronic dextran sulfate sodium (DSS)-induced colitis in mice. Clin Exp Immunol 116: 238-245 https://doi.org/10.1046/j.1365-2249.1999.00878.x
  35. Neurath MF, Fuss I, Kelsall BL, Strober W. 1995. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 182: 1281-1290 https://doi.org/10.1084/jem.182.5.1281
  36. Schreiber S, Heing T, Thiele HG, Raedler A. 1995. Immunoregulatory role of interleukin 10 in patient with inflammatory bowel disease. Gastroenterology 108: 1434- 1444 https://doi.org/10.1016/0016-5085(95)90692-4
  37. Seder RA, Gazzinelli R, Sher A, Paul WE. 1993. Interleukin- 12 acts directly on CD4+ T cells to enhance priming for interferon {gamma} production and diminishes interleukin-4 inhibition of such priming. Proc Natl Acad Sci USA 90: 10188-10192 https://doi.org/10.1073/pnas.90.21.10188
  38. Metcalfe DD. 1991. Food allergy. Current Opinion Immunol 3: 881-886 https://doi.org/10.1016/S0952-7915(05)80007-X
  39. Moutoussamy S, Kelly PA, Finidori J. 1998. Growth-hormone-receptor and cytokine-receptor-family signaling. Eur J Biochem 255: 1-11 https://doi.org/10.1046/j.1432-1327.1998.2550001.x
  40. Imada K, Leonard WJ. 2000. The Jak-STAT pathway. Mol Immunol 37: 1-11 https://doi.org/10.1016/S0161-5890(00)00018-3
  41. Bromberg J, Chen X. 2001. STAT proteins: signal tranducers and activators of transcription. Methods Enzymol 333: 138-151 https://doi.org/10.1016/S0076-6879(01)33052-5

Cited by

  1. Effects of natural raw meal (NRM) on high-fat diet and dextran sulfate sodium (DSS)-induced ulcerative colitis in C57BL/6J mice vol.9, pp.6, 2015, https://doi.org/10.4162/nrp.2015.9.6.619