DOI QR코드

DOI QR Code

Anti-bacterial effects of enzymatically-isolated sialic acid from glycomacropeptide in a Helicobacter pylori-infected murine model

  • 투고 : 2016.09.23
  • 심사 : 2016.11.08
  • 발행 : 2017.02.01

초록

BACKGROUND/OBJECTIVES: Helicobacter pylori (H. pylori) colonization of the stomach mucosa and duodenum is the major cause of acute and chronic gastroduodenal pathology in humans. Efforts to find effective anti-bacterial strategies against H. pylori for the non-antibiotic control of H. pylori infection are urgently required. In this study, we used whey to prepare glycomacropeptide (GMP), from which sialic acid (G-SA) was enzymatically isolated. We investigated the anti-bacterial effects of G-SA against H. pylori in vitro and in an H. pylori-infected murine model. MATERIALS/METHODS: The anti-bacterial activity of G-SA was measured in vitro using the macrodilution method, and interleukin-8 (IL-8) production was measured in H. pylori and AGS cell co-cultures by ELISA. For in vivo study, G-SA 5 g/kg body weight (bw)/day and H. pylori were administered to mice three times over one week. After one week, G-SA 5 g/kg bw/day alone was administered every day for one week. Tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), IL-$1{\beta}$, IL-6, and IL-10 levels were measured by ELISA to determine the anti-inflammatory effects of G-SA. In addition, real-time PCR was performed to measure the genetic expression of cytotoxin-associated gene A (cagA). RESULTS: G-SA inhibited the growth of H. pylori and suppressed IL-8 production in H. pylori and in AGS cell co-cultures in vitro. In the in vivo assay, administration of G-SA reduced levels of IL-$1{\beta}$ and IL-6 pro-inflammatory cytokines whereas IL-10 level increased. Also, G-SA suppressed the expression of cagA in the stomach of H. pylori-infected mice. CONCLUSION: G-SA possesses anti-H. pylori activity as well as an anti-H. pylori-induced gastric inflammatory effect in an experimental H. pylori-infected murine model. G-SA has potential as an alternative to antibiotics for the prevention of H. pylori infection and H. pylori-induced gastric disease prevention.

키워드

참고문헌

  1. Suerbaum S, Michetti P. Helicobacter pylori infection. N Engl J Med 2002;347:1175-86. https://doi.org/10.1056/NEJMra020542
  2. Venerito M, Vasapolli R, Rokkas T, Malfertheiner P. Helicobacter pylori and gastrointestinal malignancies. Helicobacter 2015;20 Suppl 1:36-9. https://doi.org/10.1111/hel.12255
  3. Cover TL, Blaser MJ. Helicobacter pylori infection, a paradigm for chronic mucosal inflammation: pathogenesis and implications for eradication and prevention. Adv Intern Med 1996;41:85-117.
  4. Boren T, Falk P, Roth KA, Larson G, Normark S. Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 1993;262:1892-5. https://doi.org/10.1126/science.8018146
  5. Kobayashi Y, Okazaki K, Murakami K. Adhesion of Helicobacter pylori to gastric epithelial cells in primary cultures obtained from stomachs of various animals. Infect Immun 1993;61:4058-63.
  6. Bodger K, Crabtree JE. Helicobacter pylori and gastric inflammation. Br Med Bull 1998;54:139-50. https://doi.org/10.1093/oxfordjournals.bmb.a011664
  7. Huang J, O'Toole PW, Doig P, Trust TJ. Stimulation of interleukin-8 production in epithelial cell lines by Helicobacter pylori. Infect Immun 1995;63:1732-8.
  8. Harris PR, Mobley HL, Perez-Perez GI, Blaser MJ, Smith PD. Helicobacter pylori urease is a potent stimulus of mononuclear phagocyte activation and inflammatory cytokine production. Gastroenterology 1996;111:419-25. https://doi.org/10.1053/gast.1996.v111.pm8690207
  9. Jones KR, Whitmire JM, Merrell DS. A tale of two toxins: Helicobacter pylori CagA and VacA modulate host pathways that impact disease. Front Microbiol 2010;1:115.
  10. Kaji T, Ishihara S, Ashizawa N, Hamamoto N, Endo H, Fukuda R, Adachi K, Watanabe M, Nakao M, Kinoshita Y. Adherence of Helicobacter pylori to gastric epithelial cells and mucosal inflammation. J Lab Clin Med 2002;139:244-50. https://doi.org/10.1067/mlc.2002.122280
  11. Varki NM, Varki A. Diversity in cell surface sialic acid presentations: implications for biology and disease. Lab Invest 2007;87:851-7. https://doi.org/10.1038/labinvest.3700656
  12. Vimr ER, Kalivoda KA, Deszo EL, Steenbergen SM. Diversity of microbial sialic acid metabolism. Microbiol Mol Biol Rev 2004;68:132-53. https://doi.org/10.1128/MMBR.68.1.132-153.2004
  13. Carson CF, Riley TV. Non-antibiotic therapies for infectious diseases. Commun Dis Intell Q Rep 2003;27 Suppl:S143-6.
  14. Kamiji MM, de Oliveira RB. Non-antibiotic therapies for Helicobacter pylori infection. Eur J Gastroenterol Hepatol 2005;17:973-81. https://doi.org/10.1097/00042737-200509000-00014
  15. Yang JC, Shun CT, Chien CT, Wang TH. Effective prevention and treatment of Helicobacter pylori infection using a combination of catechins and sialic acid in AGS cells and BALB/c mice. J Nutr 2008;138:2084-90. https://doi.org/10.3945/jn.108.090985
  16. Wang YC. Medicinal plant activity on Helicobacter pylori related diseases. World J Gastroenterol 2014;20:10368-82. https://doi.org/10.3748/wjg.v20.i30.10368
  17. Ando T, Kusugami K, Ohsuga M, Shinoda M, Sakakibara M, Saito H, Fukatsu A, Ichiyama S, Ohta M. Interleukin-8 activity correlates with histological severity in Helicobacter pylori-associated antral gastritis. Am J Gastroenterol 1996;91:1150-6.
  18. Lee A, O'Rourke J, De Ungria MC, Robertson B, Daskalopoulos G, Dixon MF. A standardized mouse model of Helicobacter pylori infection: introducing the Sydney strain. Gastroenterology 1997;112:1386-97. https://doi.org/10.1016/S0016-5085(97)70155-0
  19. Shimoyama T, Crabtree JE. Bacterial factors and immune pathogenesis in Helicobacter pylori infection. Gut 1998;43 Suppl 1:S2-5. https://doi.org/10.1136/gut.43.2008.S2
  20. Simon PM, Goode PL, Mobasseri A, Zopf D. Inhibition of Helicobacter pylori binding to gastrointestinal epithelial cells by sialic acid-containing oligosaccharides. Infect Immun 1997;65:750-7.
  21. Kudo T, Lu H, Wu JY, Ohno T, Wu MJ, Genta RM, Graham DY, Yamaoka Y. Pattern of transcription factor activation in Helicobacter pylori-infected Mongolian gerbils. Gastroenterology 2007;132:1024-38. https://doi.org/10.1053/j.gastro.2007.01.009
  22. Yamamoto T, Kita M, Ohno T, Iwakura Y, Sekikawa K, Imanishi J. Role of tumor necrosis factor-alpha and interferon-gamma in Helicobacter pylori infection. Microbiol Immunol 2004;48:647-54. https://doi.org/10.1111/j.1348-0421.2004.tb03474.x
  23. Thalmaier U, Lehn N, Pfeffer K, Stolte M, Vieth M, Schneider-Brachert W. Role of tumor necrosis factor alpha in Helicobacter pylori gastritis in tumor necrosis factor receptor 1-deficient mice. Infect Immun 2002;70:3149-55. https://doi.org/10.1128/IAI.70.6.3149-3155.2002
  24. Bodger K, Wyatt JI, Heatley RV. Gastric mucosal secretion of interleukin-10: relations to histopathology, Helicobacter pylori status, and tumour necrosis factor-alpha secretion. Gut 1997;40:739-44. https://doi.org/10.1136/gut.40.6.739
  25. Bodger K, Bromelow K, Wyatt JI, Heatley RV. Interleukin 10 in Helicobacter pylori associated gastritis: immunohistochemical localisation and in vitro effects on cytokine secretion. J Clin Pathol 2001;54:285-92. https://doi.org/10.1136/jcp.54.4.285
  26. Berg DJ, Lynch NA, Lynch RG, Lauricella DM. Rapid development of severe hyperplastic gastritis with gastric epithelial dedifferentiation in Helicobacter felis-infected IL-10(-/-) mice. Am J Pathol 1998;152:1377-86.
  27. Linden SK, Wickstrom C, Lindell G, Gilshenan K, Carlstedt I. Four modes of adhesion are used during Helicobacter pylori binding to human mucins in the oral and gastric niches. Helicobacter 2008;13:81-93. https://doi.org/10.1111/j.1523-5378.2008.00587.x
  28. Nakayama J. Helicobacter pylori growth assay for glycans. In: Taniguchi N, Suzuki A, Ito Y, Narimatsu H, Kawasaki T, Hase S, editors. Experimental Glycoscience. Tokyo: Springer; 2008. p.227-9.
  29. Lee H, Wang P, Hoshino H, Ito Y, Kobayashi M, Nakayama J, Seeberger PH, Fukuda M. ${\alpha}1$,4GlcNAc-capped mucin-type O-glycan inhibits cholesterol ${\alpha}$-glucosyltransferase from Helicobacter pylori and suppresses H. pylori growth. Glycobiology 2008;18:549-58. https://doi.org/10.1093/glycob/cwn037

피인용 문헌

  1. Glycomacropeptide: A Bioactive Milk Derivative to Alleviate Metabolic Syndrome Outcomes vol.34, pp.3, 2017, https://doi.org/10.1089/ars.2019.7994
  2. Antioxidant, antimicrobial and anticarcinogenic activities of bovine milk proteins and their hydrolysates - A review vol.127, pp.None, 2022, https://doi.org/10.1016/j.idairyj.2021.105208