Macrophage activation by glycoprotein isolated from Dioscorea batatas

  • Huong, Pham Thi Thu ;
  • Jeon, Young-Jin
  • Received : 2011.04.23
  • Accepted : 2011.08.15
  • Published : 2011.09.01


We demonstrate that glycoprotein isolated from Dioscorea batatas (GDB) activates macrophage function. Analysis of the infiltration of macrophages into peritoneal cavity showed GDB treatment significantly increased the recruitment of macrophages into the peritoneal cavity. In order to further confirm and investigate the mechanism of GDB on macrophage activation, we analyzed the effects of GDB on the cytokine expression including IL-$1{\beta}$, TNF-${\alpha}$, and IL-6 in mouse peritoneal macrophages. GDB increased the expression of IL-$1{\beta}$, TNF-${\alpha}$, and IL-6. Cytokine induction by GDB was further confirmed by RT-PCR and ELISA in mouse macrophage cell line, RAW264.7 cells. Treatment of RAW264.7 cells with GDB produced strong induction of NF-${\kappa}B$ DNA binding and MAPK phosphorylation, markers for macrophage activation and important factors for cytokine gene expression. Collectively, this series of experiments indicates that GDB stimulates macrophage activation.




  1. Billack, B. (2006). Macrophage activation: role of toll-like receptors, nitric oxide, and nuclear factor kappa B. Am. J. Pharm. Educ., 70, 102.
  2. Chen, H., Wang, C., Chang, C.T. and Wang, T. (2003). Effects of Taiwanese yam (Dioscorea japonica Thunb var. pseudojaponica Yamamoto) on upper gut function and lipid metabolism in Balb/c mice. Nutrition, 19, 646-651.
  3. Gaidamashvili, M., Ohizumi, Y., Iijima, S., Takayama, T., Ogawa, T. and Muramoto, K. (2004). Characterization of the yam tuber storage proteins from Dioscorea batatas exhibiting unique lectin activities. J. Biol. Chem., 279, 26028-26035.
  4. Goyert, S.M., Ferrero, E., Rettig, W.J., Yenamandra, A.K., Obata, F. and Le Beau, M.M. (1988). The CD14 monocyte differentiation antigen maps to a region encoding growth factors and receptors. Science, 239, 497-500.
  5. Green, L.C., Wagner, D.A., Glogowski, J., Skipper, P.L., Wishnok, J.S. and Tannenbaum, S.R. (1982). Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Anal. Biochem., 126, 131-138.
  6. Huong, P.T., Lee, C.H., Li, M.H., Lee, M.Y., Kim, J.K., Lee, S.M., Seon, J.H., Lee, D.C. and Jeon, Y.J. (2011). Characterization and immunopotentiating effects of the glycoprotein isolated from dioscorea batatas. Korean J. Physiol. Pharmacol., 15, 101-106.
  7. Hibbs, J.B. Jr., Taintor, R.R. and Vavrin, Z. (1987). Macrophage cytotoxicity: role for L-arginine deiminase and imino nitrogen oxidation to nitrite. Science, 235, 473-476.
  8. Higuchi, M., Higashi, N., Taki, H. and Osawa, T. (1990). Cytolytic mechanisms of activated macrophages. Tumor necrosis factor and L-arginine-dependent mechanisms act synergistically as the major cytolytic mechanisms of activated macrophages. J. Immunol., 144, 1425-1431.
  9. Hynes, R.O. (1992). Integrins: versatility, modulation, and signaling in cell adhesion. Cell, 69, 11-25.
  10. Ip, Y.T. and Davis, R.J. (1998). Signal transduction by the c-Jun N-terminal kinase (JNK)--from inflammation to development. Curr. Opin. Cell Biol., 10, 205-219.
  11. Jeon, Y.J., Han, S.B., Ahn, K.S. and Kim, H.M. (2000). Differential activation of murine macrophages by angelan and LPS. Immunopharmacology, 49, 275-284.
  12. Jin, U.H., Kim, D.I., Lee, T.K., Lee, D.N., Kim, J.K., Lee, I.S. and Kim, C.H. (2006). Herbal formulation, Yukmi-jihang-tang-Jahage, regulates bone resorption by inhibition of phosphorylation mediated by tyrosine kinase Src and cyclooxygenase expression. J. Ethnopharmacol., 106, 333-343.
  13. Klimetzek, V. and Remold, H.G. (1980). The murine bone marrow macrophage, a sensitive indicator cell for murine migration inhibitory factor and a new method for their harvest. Cell Immunol., 53, 257-266.
  14. Kopp, E.B. and Medzhitov, R. (1999). The Toll-receptor family and control of innate immunity. Curr. Opin. Immunol., 11, 13-18.
  15. Lee, K.Y. and Jeon, Y.J. (2003). Polysaccharide isolated from Poria cocos sclerotium induces NF-kappaB/Rel activation and iNOS expression in murine macrophages. Int. Immunopharmacology, 3, 1353-1362.
  16. Li, M.H., Kothandan, G., Cho, S.J., Huong, P.T., Nan, Y.H., Lee, K.Y., Shin, S.Y., Yea, S.S. and Jeon, Y.J. (2010). Magnolol inhibits LPS-induced NF-kappaB/Rel activation by blocking p38 kinase in murine macrophages. Korean J. Physiol. Pharmacol., 14, 353-358.
  17. Lowenstein, C.J., Alley, E.W., Raval, P., Snowman, A.M., Snyder, S.H., Russell, S.W. and Murphy, W.J. (1993). Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc. Natl. Acad. Sci. U.S.A., 90, 9730-9734.
  18. Pahl, H.L. (1999). Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 18, 6853-6866.
  19. Raingeaud, J., Gupta, S., Rogers, J.S., Dickens, M., Han, J., Ulevitch, R.J. and Davis, R.J. (1995). Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. J. Biol. Chem., 270, 7420-7426.
  20. Robinson, M.J. and Cobb, M.H. (1997). Mitogen-activated protein kinase pathways. Curr. Opin. Cell Biol., 9, 180-186.
  21. Stuehr, D.J. and Nathan, C.F. (1989). Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells. J. Exp. Med., 169, 1543-1555.
  22. Su, B. and Karin, M. (1996). Mitogen-activated protein kinase cascades and regulation of gene expression. Curr. Opin. Immunol., 8, 402-411.
  23. Thornton, B.P., Vetvicka, V., Pitman, M., Goldman, R.C. and Ross, G.D. (1996). Analysis of the sugar specificity and molecular location of the beta-glucan-binding lectin site of complement receptor type 3 (CD11b/CD18). J. Immunol., 156, 1235-1246.
  24. Weinstein, S.L., Sanghera, J.S., Lemke, K., DeFranco, A.L. and Pelech, S.L. (1992). Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages. J. Biol. Chem., 267, 14955-14962.
  25. Whitmarsh, A.J. and Davis, R.J. (1996). Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J. Mol. Med., 74, 589-607.
  26. Xie, Q.W., Whisnant, R. and Nathan, C. (1993). Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon-g and bacterial lipopolysaccharide. J. Exp. Med., 177, 1779-1784.


Supported by : Chosun University