Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지

Molecular Mechanism of Macrophage Activation by Exopolysaccharides from Liquid Culture of Lentinus edodes

  • Lee, Ji-Yeon (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Kim, Joo-Young (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Lee, Yong-Gyu (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University) ;
  • Rhee, Man-Hee (College of Veterinary Medicine, Kyungpook National University) ;
  • Hong, Eock-Ki (Department of Bioengineering and Technology, Kangwon National University) ;
  • Cho, Jae-Youl (School of Bioscience and Biotechnology, and Institute of Bioscience and Biotechnology, Kangwon National University)
  • Published : 2008.02.29
Download PDF
⟨ Previous Next ⟩

Abstract

Mushrooms are regarded as one of the well-known foods and biopharmaceutical materials with a great deal of interest. ${\beta}$-Glucan is the major component of mushrooms that displays various biological activities such as antidiabetic, anticancer, and antihyperlipidemic effects. In this study, we explored the molecular mechanism of its immunostimulatory potency in immune responses of macrophages, using exopolysaccharides prepared from liquid culture of Lentinus edodes. We found that fraction II (F-II), with large molecular weight protein polysaccharides, is able to strongly upregulate the phenotypic functions of macrophages such as phagocytic uptake, ROS/NO production, cytokine expression, and morphological changes. F-II triggered the nuclear translocation of NF-${\kappa}B$ and activated its upstream signaling cascades such as PI3K/Akt and MAPK pathways, as assessed by their phosphorylation levels. The function-blocking antibodies to dectin-1 and TLR-2, but not CR3, markedly suppressed F-II-mediated NO production. Therefore, our data suggest that mushroom-derived ${\beta}$-glucan may exert its immunostimulating potency via activation of multiple signaling pathways.

Keywords

References

  1. Akamatsu, S., A. Watanabe, M. Tamesada, R. Nakamura, S. Hayashi, D. Kodama, M. Kawase, and K. Yagi. 2004. Hepatoprotective effect of extracts from Lentinus edodes mycelia on dimethylnitrosamine-induced liver injury. Biol. Pharm. Bull. 27: 1957-1960 https://doi.org/10.1248/bpb.27.1957
  2. Allavena, P., M. Chieppa, P. Monti, and L. Piemonti. 2004. From pattern recognition receptor to regulator of homeostasis: The double-faced macrophage mannose receptor. Crit. Rev. Immunol. 24: 179-192 https://doi.org/10.1615/CritRevImmunol.v24.i3.20
  3. Borchers, A. T., J. S. Stern, R. M. Hackman, C. L. Keen, and M. E. Gershwin. 1999. Mushrooms, tumors, and immunity. Proc. Soc. Exp. Biol. Med. 221: 281-293
  4. Brown, G. D. 2006. Dectin-1: A signalling non-TLR patternrecognition receptor. Nat. Rev. Immunol. 6: 33-43 https://doi.org/10.1038/nri1745
  5. Brown, G. D., P. R. Taylor, D. M. Reid, J. A. Willment, D. L. Williams, L. Martinez-Pomares, S. Y. Wong, and S. Gordon. 2002. Dectin-1 is a major beta-glucan receptor on macrophages. J. Exp. Med. 196: 407-412 https://doi.org/10.1084/jem.20020470
  6. Brown, G. D., J. Herre, D. L. Williams, J. A. Willment, A. S. Marshall, and S. Gordon. 2003. Dectin-1 mediates the biological effects of beta-glucans. J. Exp. Med. 197: 1119-1124 https://doi.org/10.1084/jem.20021890
  7. Cho, H. J., J. Y. Cho, M. H. Rhee, H. S. Kim, H. S. Lee, and H. J. Park. 2007. Inhibitory effects of cordycepin (3'-deoxyadenosine), a component of Cordyceps militaris, on human platelet aggregation induced by thapsigargin. J. Microbiol. Biotechnol. 17: 1134-1138
  8. Cho, J. Y., K. U. Baik, J. H. Jung, and M. H. Park. 2000. In vitro anti-inflammatory effects of cynaropicrin, a sesquiterpene lactone, from Saussurea lappa. Eur. J. Pharmacol. 398: 399-407 https://doi.org/10.1016/S0014-2999(00)00337-X
  9. Cutolo, M. 1999. Macrophages as effectors of the immunoendocrinologic interactions in autoimmune rheumatic diseases. Ann. NY Acad Sci. 876: 32-41; discussion 41-42 https://doi.org/10.1111/j.1749-6632.1999.tb07620.x
  10. Dai, Q. and S. B. Pruett. 2006. Ethanol suppresses LPS-induced Toll-like receptor 4 clustering, reorganization of the actin cytoskeleton, and associated TNF-alpha production. Alcohol. Clin. Exp. Res. 30: 1436-1444 https://doi.org/10.1111/j.1530-0277.2006.00172.x
  11. Dillon, S., S. Agrawal, K. Banerjee, J. Letterio, T. L. Denning, K. Oswald-Richter, D. J. Kasprowicz, K. Kellar, J. Pare, T. van Dyke, S. Ziegler, D. Unutmaz, and B. Pulendran. 2006. Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance. J. Clin. Invest. 116: 916-928 https://doi.org/10.1172/JCI27203
  12. Dong, Q., L. M. Jia, and J. N. Fang. 2006. A beta-D-glucan isolated from the fruiting bodies of Hericium erinaceus and its aqueous conformation. Carbohydr. Res. 341: 791-795 https://doi.org/10.1016/j.carres.2006.01.022
  13. Doyle, S. L. and L. A. O'Neill. 2006. Toll-like receptors: From the discovery of NFkappaB to new insights into transcriptional regulations in innate immunity. Biochem. Pharmacol. 72: 1102- 1113
  14. Duperrier, K., A. Eljaafari, C. Dezutter-Dambuyant, C. Bardin, C. Jacquet, K. Yoneda, D. Schmitt, L. Gebuhrer, and D. Rigal. 2000. Distinct subsets of dendritic cells resembling dermal DCs can be generated in vitro from monocytes, in the presence of different serum supplements. J. Immunol. Methods 238: 119-131 https://doi.org/10.1016/S0022-1759(00)00147-2
  15. Evans, S. E., P. Y. Hahn, F. McCann, T. J. Kottom, Z. V. Pavlovic, and A. H. Limper. 2005. Pneumocystis cell wall betaglucans stimulate alveolar epithelial cell chemokine generation through nuclear factor-kappaB-dependent mechanisms. Am. J. Respir. Cell Mol. Biol. 32: 490-497 https://doi.org/10.1165/rcmb.2004-0300OC
  16. Fang, N., Q. Li, S. Yu, J. Zhang, L. He, M. J. Ronis, and T. M. Badger. 2006. Inhibition of growth and induction of apoptosis in human cancer cell lines by an ethyl acetate fraction from shiitake mushrooms. J. Altern. Complement. Med. 12: 125-132 https://doi.org/10.1089/acm.2006.12.125
  17. Fishman, P., S. Bar-Yehuda, L. Madi, L. Rath-Wolfson, A. Ochaion, S. Cohen, and E. Baharav. 2006. The PI3K-NFkappaB signal transduction pathway is involved in mediating the anti-inflammatory effect of IB-MECA in adjuvant-induced arthritis. Arthritis Res. Ther. 8: R33 https://doi.org/10.1186/ar1887
  18. Gordon, S. 2002. Pattern recognition receptors: Doubling up for the innate immune response. Cell 111: 927-930 https://doi.org/10.1016/S0092-8674(02)01201-1
  19. Gordon, S. B. and R. C. Read. 2002. Macrophage defences against respiratory tract infections. Br. Med. Bull. 61: 45-61 https://doi.org/10.1093/bmb/61.1.45
  20. Hahn, P. Y., S. E. Evans, T. J. Kottom, J. E. Standing, R. E. Pagano, and A. H. Limper. 2003. Pneumocystis carinii cell wall beta-glucan induces release of macrophage inflammatory protein-2 from alveolar epithelial cells via a lactosylceramidemediated mechanism. J. Biol. Chem. 278: 2043-2050 https://doi.org/10.1074/jbc.M209715200
  21. Hardy, K. and N. H. Hunt. 2004. Effects of a redox-active agent on lymphocyte activation and early gene expression patterns. Free Radic. Biol. Med. 37: 1550-1563 https://doi.org/10.1016/j.freeradbiomed.2004.07.020
  22. Herre, J., S. Gordon, and G. D. Brown. 2004. Dectin-1 and its role in the recognition of beta-glucans by macrophages. Mol. Immunol. 40: 869-876 https://doi.org/10.1016/j.molimm.2003.10.007
  23. Hoebe, K., Z. Jiang, P. Georgel, K. Tabeta, E. Janssen, X. Du, and B. Beutler. 2006. TLR signaling pathways: Opportunities for activation and blockade in pursuit of therapy. Curr. Pharm. Des. 12: 4123-4134 https://doi.org/10.2174/138161206778743466
  24. Hsu, T. C., M. R. Young, J. Cmarik, and N. H. Colburn. 2000. Activator protein 1 (AP-1)- and nuclear factor kappaB (NFkappaB)- dependent transcriptional events in carcinogenesis. Free Radic. Biol. Med. 28: 1338-1348 https://doi.org/10.1016/S0891-5849(00)00220-3
  25. Jung, K. K., H. S. Lee, J. Y. Cho, W. C. Shin, M. H. Rhee, T. G. Kim, J. H. Kang, S. H. Kim, S. Hong, and S. Y. Kang. 2006. Inhibitory effect of curcumin on nitric oxide production from lipopolysaccharide-activated primary microglia. Life Sci. 79: 2022-2031 https://doi.org/10.1016/j.lfs.2006.06.048
  26. Kataoka, K., T. Muta, S. Yamazaki, and K. Takeshige. 2002. Activation of macrophages by linear $(1\rightarrow 3)-beta-D-glucans$. Implications for the recognition of fungi by innate immunity. J. Biol. Chem. 277: 36825-36831 https://doi.org/10.1074/jbc.M206756200
  27. Kupfahl, C., G. Geginat, and H. Hof. 2006. Lentinan has a stimulatory effect on innate and adaptive immunity against murine Listeria monocytogenes infection. Int. Immunopharmacol. 6: 686-696 https://doi.org/10.1016/j.intimp.2005.10.008
  28. Kweon, M. H., W. J. Lim, H. C. Yang, and H. C. Sung. 2000. Characterization of two glucans activating an alternative complement pathway from the fruiting bodies of mushroom Pleurotus ostreatus. J. Microbiol. Biotechnol. 10: 267-271
  29. Lull, C., H. J. Wichers, and H. F. Savelkoul. 2005. Antiinflammatory and immunomodulating properties of fungal metabolites. Mediators Inflamm. 2005: 63-80 https://doi.org/10.1155/MI.2005.63
  30. Mayell, M. 2001. Maitake extracts and their therapeutic potential. Altern. Med. Rev. 6: 48-60
  31. Morand, E. F. and M. Leech. 2005. Macrophage migration inhibitory factor in rheumatoid arthritis. Front. Biosci. 10: 12-22 https://doi.org/10.2741/1501
  32. Nair, P. K., S. J. Melnick, R. Ramachandran, E. Escalon, and C. Ramachandran. 2006. Mechanism of macrophage activation by (1,4)-alpha-D-glucan isolated from Tinospora cordifolia. Int. Immunopharmacol. 6: 1815-1824 https://doi.org/10.1016/j.intimp.2006.07.028
  33. Olsson, S. and R. Sundler. 2007. The macrophage beta-glucan receptor mediates arachidonate release induced by zymosan: Essential role for Src family kinases. Mol. Immunol. 44: 1509-1515 https://doi.org/10.1016/j.molimm.2006.09.004
  34. Olynych, T. J., D. L. Jakeman, and J. S. Marshall. 2006. Fungal zymosan induces leukotriene production by human mast cells through a dectin-1-dependent mechanism. J. Allergy Clin. Immunol. 118: 837-843 https://doi.org/10.1016/j.jaci.2006.06.008
  35. Park, S. K., G. Y. Kim, J. Y. Lim, J. Y. Kwak, Y. S. Bae, J. D. Lee, Y. H. Oh, S. C. Ahn, and Y. M. Park. 2003. Acidic polysaccharides isolated from Phellinus linteus induce phenotypic and functional maturation of murine dendritic cells. Biochem. Biophys. Res. Commun. 312: 449-458 https://doi.org/10.1016/j.bbrc.2003.10.136
  36. Rogers, N. C., E. C. Slack, A. D. Edwards, M. A. Nolte, O. Schulz, E. Schweighoffer, D. L. Williams, S. Gordon, V. L. Tybulewicz, G. D. Brown, and C. Reis e Sousa. 2005. Syk-dependent cytokine induction by dectin-1 reveals a novel pattern recognition pathway for C type lectins. Immunity 22: 507-517 https://doi.org/10.1016/j.immuni.2005.03.004
  37. Sato, M., H. Sano, D. Iwaki, K. Kudo, M. Konishi, H. Takahashi, T. Takahashi, H. Imaizumi, Y. Asai, and Y. Kuroki. 2003. Direct binding of Toll-like receptor 2 to zymosan, and zymosan-induced NF-kappa B activation and TNF-alpha secretion are down-regulated by lung collectin surfactant protein A. J. Immunol. 171: 417-425 https://doi.org/10.4049/jimmunol.171.1.417
  38. Schaefer, L., A. Babelova, E. Kiss, H. J. Hausser, M. Baliova, M. Krzyzankova, G. Marsche, M. F. Young, D. Mihalik, M. Gotte, E. Malle, R. M. Schaefer, and H. J. Grone. 2005. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. J. Clin. Invest. 115: 2223-2233 https://doi.org/10.1172/JCI23755
  39. Schroder, N. W., B. Opitz, N. Lamping, K. S. Michelsen, U. Zahringer, U. B. Gobel, and R. R. Schumann. 2000. Involvement of lipopolysaccharide binding protein, CD14, and Toll-like receptors in the initiation of innate immune responses by Treponema glycolipids. J. Immunol. 165: 2683-2693 https://doi.org/10.4049/jimmunol.165.5.2683
  40. Son, C. G., J. W. Shin, J. H. Cho, C. K. Cho, C. H. Yun, W. Chung, and S. H. Han. 2006. Macrophage activation and nitric oxide production by water soluble components of Hericium erinaceum. Int. Immunopharmacol. 6: 1363-1369 https://doi.org/10.1016/j.intimp.2006.03.005
  41. Sorensen, H. R., A. S. Meyer, and S. Pedersen. 2003. Enzymatic hydrolysis of water-soluble wheat arabinoxylan. 1. Synergy between alpha-L-arabinofuranosidases, endo-1,4-beta-xylanases, and beta-xylosidase activities. Biotechnol. Bioeng. 81: 726-731 https://doi.org/10.1002/bit.10519
  42. Stuhlmuller, B., U. Ungethum, S. Scholze, L. Martinez, M. Backhaus, H. G. Kraetsch, R. W. Kinne, and G. R. Burmester. 2000. Identification of known and novel genes in activated monocytes from patients with rheumatoid arthritis. Arthritis Rheum. 43: 775-790 https://doi.org/10.1002/1529-0131(200004)43:4<775::AID-ANR8>3.0.CO;2-7
  43. Taylor, P. R., S. V. Tsoni, J. A. Willment, K. M. Dennehy, M. Rosas, H. Findon, K. Haynes, C. Steele, M. Botto, S. Gordon, and G. D. Brown. 2007. Dectin-1 is required for beta-glucan recognition and control of fungal infection. Nat. Immunol. 8: 31-38 https://doi.org/10.1038/ni1408
  44. Trinchieri, G. and A. Sher. 2007. Cooperation of Toll-like receptor signals in innate immune defence. Nat. Rev. Immunol. 7: 179-190 https://doi.org/10.1038/nri2038
  45. Wu, M. J., T. L. Cheng, S. Y. Cheng, T. W. Lian, L. Wang, and S. Y. Chiou. 2006. Immunomodulatory properties of Grifola frondosa in submerged culture. J. Agric. Food Chem. 54: 2906-2914 https://doi.org/10.1021/jf052893q
  46. Yadav, M. and J. S. Schorey. 2006. The beta-glucan receptor dectin-1 functions together with TLR2 to mediate macrophage activation by mycobacteria. Blood 108: 3168-3175 https://doi.org/10.1182/blood-2006-05-024406
  47. Yrlid, U., M. Svensson, C. Johansson, and M. J. Wick. 2000. Salmonella infection of bone marrow-derived macrophages and dendritic cells: Influence on antigen presentation and initiating an immune response. FEMS Immunol. Med. Microbiol. 27: 313-320 https://doi.org/10.1111/j.1574-695X.2000.tb01445.x
  48. Zhao, M. W., W. Q. Liang, D. B. Zhang, N. Wang, C. G. Wang, and Y. J. Pan. 2007. Cloning and characterization of squalene synthase (SQS) gene from Ganoderma lucidum. J. Microbiol. Biotechnol. 17: 1106-1112
  49. Zheng, R., S. Jie, D. Hanchuan, and W. Moucheng. 2005. Characterization and immunomodulating activities of polysaccharide from Lentinus edodes. Int. Immunopharmacol. 5: 811-820