Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Sulforaphane Enhances MHC Class II-Restricted Presentation of Exogenous Antigens

  • Received : 2010.11.30
  • Accepted : 2010.12.28
  • Published : 2011.01.31
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Abstract

Sulforaphane is an isothiocyanate found in cruciferous vegetables that has been reported to be an effective cancer preventive agent inducing growth arrest and/or cell death in cancer cells of various organs. This paper reports that sulforaphane exerts immunomodulatory activity on the MHC-restricted antigen presenting function. Sulforaphane efficiently increased the class II-restricted presentation of an exogenous antigen, ovalbumin (OVA), in both dendritic cells (DCs) and peritoneal macrophages in vitro. The class II-restricted OVA presentation-enhancing activity of sulforaphane was also confirmed using mice that had been injected with sulforaphane followed by soluble OVA. On the other hand, sulforaphane did not affect the class I-restricted presentation of exogenous OVA at concentrations that increase the class II-restricted antigen presentation. At a high concentration ($20\;{\mu}M$), sulforaphane inhibited the class I-restricted presentation of exogenous OVA. Sulforaphane did not affect the phagocytic activity of the DCs, and the cell surface expression of total H-$2K^b$, B7-1, B7-2 and CD54 molecules, even though it increased the expression of I-$A^b$ molecules to a barely discernable level. These results show that sulforaphane increases the class II-restricted antigen presenting function preferentially, and might provide a novel insight into the mechanisms of the anti-cancer effects of sulforaphane.

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References

  1. Ambrosone, C. B., McCann, S. E., Freudenheim, J. L., Marshall, J. R., Zhang, Y. and Shields, P. G. (2004) Breast cancer risk in premenopausal women is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GST genotype. J. Nutr. 134, 1134-1138.
  2. Bevan, M. J. (1976) Cross-priming for a secondary cytotoxic response to minor H antigens with H-2 congenic cells which do not crossreact in the cytotoxic assay. J. Immunol. 185, 1361-1366.
  3. Bones, A. M. and Rossiter, J. T. (2006) The enzymic and chemically induced decomposition of glucosinolates. Phytochemistry 67, 1053-1067. https://doi.org/10.1016/j.phytochem.2006.02.024
  4. Fimognari, C. and Hrelia, P. (2007) Sulforaphane as a promising molecule for fighting cancer. Mutat. Res. 635, 90-104. https://doi.org/10.1016/j.mrrev.2006.10.004
  5. Gamet-Payrastre, L., Li, P., Lumeau, S., Cassar, G., Dupont, M. A., Chevolleau, S., Gasc, N., Tulliez, J. and Terce, F. (2000) Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells. Cancer Res. 60, 1426-1433.
  6. Gingras, D., Gendron, M., Boivin, D., Moghrabi, A., Theoret, Y. and Beliveau, R. (2004) Induction of medulloblastoma cell apoptosis by sulforaphane, a dietary anticarcinogen from Brassica vegetables. Cancer Lett. 203, 35-43. https://doi.org/10.1016/j.canlet.2003.08.025
  7. Guermonprez, P., Valladeau, J., Zitvogel, L., Thery, C. and Amigorena, S. (2002). Antigen presentation and T cell stimulation by dendritic cells. Annu. Rev. Immunol. 20, 621-667. https://doi.org/10.1146/annurev.immunol.20.100301.064828
  8. Han, S., Song, Y., Lee, Y. H., Lee, Y. R., Lee, C. K., Cho, K. and Kim, K. (2005) Macrophage-colony stimulating factor enhances MHC-restricted presentation of exogenous antigen in dendritic cells. Cytokine 32, 187-193. https://doi.org/10.1016/j.cyto.2005.08.002
  9. Harding, C. V., Collins, D. S., Kanagawa, O. and Unanue, E. R. (1991) Liposome-encapsulated antigens engender lysosomal processing for class II MHC presentation and cytosolic processing for class I presentation. J. Immunol. 147, 2860-2863.
  10. Harding, C. V. and Song, R. (1994) Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J. Immunol. 153, 4925-4933.
  11. Harding, C. V. (1995) Phagocytic processing of antigens for presentation by MHC molecules. Trends Cell Biol. 5, 105-109. https://doi.org/10.1016/S0962-8924(00)88959-X
  12. Heath, W. R. and Carbone, F. R. (2001) Cross-presentation in viral immunity and self-tolerance. Nat. Rev. Immunol. 1, 126-134. https://doi.org/10.1038/35100512
  13. Herman-Antosiewicz, A., Johnson, D. E. and Singh, S. V. (2006) Sulforaphane causes autophagy to inhibit release of cytochrome C and apoptosis in human prostate cancer cells. Cancer Res. 66, 5828-5835. https://doi.org/10.1158/0008-5472.CAN-06-0139
  14. Huang, A. Y., Golumbek, P., Ahmadzadeh, M., Jaffee, E., Pardoll, D. and Levitsky, H. (1994) Role of bone marrow-derived cells in presenting MHC class I-restricted tumor antigens. Science 264, 961-965. https://doi.org/10.1126/science.7513904
  15. Jin, C. Y., Moon, D. O., Lee, J. D., Heo, M. S., Choi, Y. H., Lee, C. M., Park, Y. M. and Kim, G. Y. (2007) Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis through downregulation of ERK and Akt in lung adenocarcinoma A549 cells. Carcinogenesis 28, 1058-1066.
  16. Kim, H. J., Barajas, B., Wang, M. and Nel, A. E. (2008) Nrf2 activation by sulforaphane restores the age-related decrease of T(H)1 immunity: role of dendritic cells. J. Allergy Clin. Immunol. 121, 1255-1261. https://doi.org/10.1016/j.jaci.2008.01.016
  17. Kolonel, L. N., Hankin, J. H., Whittemore, A. S., Wu, A. H., Gallagher, R. P., Wilkens, L. R., John, E. M., Howe, G. R., Dreon, D. M., West, D. W. and Paffenbarger, R. S. Jr. (2000) Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study. Cancer Epidemiol. Biomarkers Prev. 9, 795-804.
  18. Lee, J. K., Lee, M. K., Yun, Y. P., Kim, Y., Kim, J. S., Kim, Y. S., Kim, J. S., Kim, Y. S., Kim, K., Han, S. S. and Lee, C. K. (2001) Acemannan purifi ed from Aloe vera induces phenotypic and functional maturation of immature dendritic cells. Int. Immunopharmacol. 1, 1275-1284. https://doi.org/10.1016/S1567-5769(01)00052-2
  19. Lee, Y. R., Yang, I. H., Lee, Y. H., Im, S. A., Song, S., Li, H., Han, K., Kim, K., Eo, S. K. and Lee, C. K. (2005) Cyclosporin A and tacrolimus, but not rapamycin, inhibit MHC-restricted antigen presentation pathways in dendritic cells. Blood 105, 3951-3955. https://doi.org/10.1182/blood-2004-10-3927
  20. Lee, Y. H., Lee, Y. R., Im, S. A., Park, S. I., Kim, K. H., Gerelchuluun, T., Song, S., Kim, K. and Lee, C. K. (2007) Calcineurin inhibitors block MHC-restricted antigen presentation in vivo. J. Immunol. 179, 5711-5716. https://doi.org/10.4049/jimmunol.179.9.5711
  21. Lee, Y. R., Lee, Y. H., Im, S. A., Yang, I. H., Ahn, G. W., Kim, K. and Lee, J. K. (2010) Biodegradable nanoparticles containing TLR3 or TLR9 agonists together with antigen enhance MHC-restricted presentation of the antigen. Arch. Parm. Sci. 33, 1859-1866.
  22. Maheo, K., Morel, F., Langouet, S., Kramer, H., Le, F. E., Ketterer, B. and Guillouzo, A. (1997) Inhibition of cytochromes P-450 and induction of glutathione S-transferases by sulforaphane in primary human and rat hepatocytes. Cancer Res. 57, 3649-3652.
  23. Myzak, M. C. and Dashwood, R. H. (2006) Chemoprotection by sulforaphane: keep one eye beyond Keap1. Cancer Lett. 233, 208-218. https://doi.org/10.1016/j.canlet.2005.02.033
  24. Parnaud, G., Li, P., Cassar, G., Rouimi, P., Tulliez, J., Combaret, L. and Gamet-Payrastre, L. (2004) Mechanism of sulforaphane-induced cell cycle arrest and apoptosis in human colon cancer cells. Nutr. Cancer 48, 198-206. https://doi.org/10.1207/s15327914nc4802_10
  25. Pham, N. A., Jacobberger, J. W., Schimmer, A. D., Cao, P., Gronda, M. and Hedley, D. W. (2004) The dietary isothiocyanate sulforaphane targets pathways of apoptosis, cell cycle arrest, and oxidative stress in human pancreatic cancer cells and inhibits tumor growth in severe combined immunodeficient mice. Mol. Cancer Ther. 3, 1239-1248.
  26. Pledgie-Tracy, A., Sobolewski, M. D. and Davidson, N. E. (2007) Sulforaphane induces cell type-specific apoptosis in human breast cancer cell lines. Mol. Cancer Ther. 6, 1013-1021.
  27. Posner, G. H., Cho, C. G., Green, J. V., Zhang, Y. and Talalay, P. (1994) Design and synthesis of bifunctional isothiocyanate analogs of sulforaphane: correlation between structure and potency as inducers of anticarcinogenic detoxication enzymes. J. Med. Chem. 37, 170-176. https://doi.org/10.1021/jm00027a021
  28. Shen, Z., Reznikoff, G., Dranoff, G. and Rock, K. L. (1997) Cloned dendritic cells can present exogenous antigens on both MHC class I and class II molecules. J. Immunol. 158, 2723-2730.
  29. Sigal, L. J., Crotty, S., Andino, R. and Rock, K. L. (1999) Cytotoxic T-cell immunity to virus-infected non-haematopoietic cells requires presentation of exogenous antigen. Nature 398, 77-80. https://doi.org/10.1038/18038
  30. Singh, S. V., Srivastava, S. K., Choi, S., Lew, K. L., Antosiewicz, J., Xiao, D., Zeng, Y., Watkins, S. C., Johnson, C. S., Trump, D. L., Lee, Y. J., Xiao, H. and Herman-Antosiewicz, A. (2005) Sulforaphane-induced cell death in human prostate cancer cells is initiated by reactive oxygen species. J. Biol. Chem. 280, 19911-19924. https://doi.org/10.1074/jbc.M412443200
  31. Singh, S. V., Warin, R., Xiao, D., Powolny, A. A., Stan, S. D., Arlotti, J. A., Zeng, Y., Hahm, E. R., Marynowski, S. W., Bommareddy, A., Desai, D., Amin, S., Parise, R. A., Beumer, J. H. and Chambers, W. H. (2009) Sulforaphane inhibits prostate carcinogenesis and pulmonary metastasis in TRAMP mice in association with increased cytotoxicity of natural killer cells. Cancer Res. 69, 2117-2125.
  32. Thejass, P. and Kuttan, G. (2006a) Antimetastatic activity of Sulforaphane. Life Sci. 78, 3043-3050. https://doi.org/10.1016/j.lfs.2005.12.038
  33. Thejass, P. and Kuttan, G. (2006b) Augmentation of natural killer cell and antibody-dependent cellular cytotoxicity in BALB/c mice by sulforaphane, a naturally occurring isothiocyanate from broccoli through enhanced production of cytokines IL-2 and IFN-gamma. Immunopharmacol. Immunotoxicol. 28, 443-457. https://doi.org/10.1080/08923970600928049
  34. Thejass, P. and Kuttan, G. (2007) Immunomodulatory activity of Sulforaphane, a naturally occurring isothiocyanate from broccoli (Brassica oleracea). Phytomedicine 14, 538-545. https://doi.org/10.1016/j.phymed.2006.09.013
  35. Verhoeven, D. T., Goldbohm, R. A., van, P. G., Verhagen, H. and van den Brandt, P. A. (1996) Epidemiological studies on brassica vegetables and cancer risk. Cancer Epidemiol. Biomarkers Prev. 5, 733-748.
  36. Yang, C. S., Smith, T. J. and Hong, J. Y. (1994) Cytochrome P-450 enzymes as targets for chemoprevention against chemical carcinogenesis and toxicity: opportunities and limitations. Cancer Res. 51, 982-1986.
  37. Zhang, Y., Kensler, T. W., Cho, C. G., Posner, G. H. and Talalay, P. (1994) Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc. Natl. Acad. Sci. USA. 91, 3147-3150. https://doi.org/10.1073/pnas.91.8.3147
  38. Zhu, J. and Paul, W. E. (2008) CD4 T cells: fates, functions, and faults. Blood 112, 1557-1569. https://doi.org/10.1182/blood-2008-05-078154

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