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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

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.

Keywords

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 premenopausalwomen is inversely associated with consumption of broccoli, a source of isothiocyanates, but is not modified by GSTgenotype. J. Nutr. 134, 1134-1138.
  2. Bevan, M. J. (1976) Cross-priming for a secondary cytotoxic responseto minor H antigens with H-2 congenic cells which do not crossreactin the cytotoxic assay. J. Immunol. 185, 1361-1366.
  3. Bones, A. M. and Rossiter, J. T. (2006) The enzymic and chemically induceddecomposition 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 moleculefor 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 arrestand apoptosis in HT29 human colon cancer cells. Cancer Res.60, 1426-1433.
  6. Gingras, D., Gendron, M., Boivin, D., Moghrabi, A., Theoret, Y. andBeliveau, R. (2004) Induction of medulloblastoma cell apoptosis bysulforaphane, 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 dendriticcells. 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-restrictedpresentation of exogenous antigen in dendritic cells. Cytokine32, 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 processingfor class II MHC presentation and cytosolic processing for class Ipresentation. J. Immunol. 147, 2860-2863.
  10. Harding, C. V. and Song, R. (1994) Phagocytic processing of exogenousparticulate antigens by macrophages for presentation byclass I MHC molecules. J. Immunol. 153, 4925-4933.
  11. Harding, C. V. (1995) Phagocytic processing of antigens for presentationby 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 immunityand 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) Sulforaphanecauses autophagy to inhibit release of cytochrome Cand 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 presentingMHC 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 tumornecrosis factor-related apoptosis-inducing ligand-mediated apoptosisthrough downregulation of ERK and Akt in lung adenocarcinomaA549 cells. Carcinogenesis 28, 1058-1066.
  16. Kim, H. J., Barajas, B., Wang, M. and Nel, A. E. (2008) Nrf2 activationby 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) Acemannanpurifi ed from Aloe vera induces phenotypic and functionalmaturation 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 presentationpathways 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 inhibitorsblock 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. andLee, J. K. (2010) Biodegradable nanoparticles containing TLR3 orTLR9 agonists together with antigen enhance MHC-restricted presentationof 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 andinduction of glutathione S-transferases by sulforaphane in primaryhuman 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. andGamet-Payrastre, L. (2004) Mechanism of sulforaphane-inducedcell 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 sulforaphanetargets pathways of apoptosis, cell cycle arrest, and oxidativestress in human pancreatic cancer cells and inhibits tumor growthin severe combined immunodeficient mice. Mol. Cancer Ther. 3,1239-1248.
  26. Pledgie-Tracy, A., Sobolewski, M. D. and Davidson, N. E. (2007) Sulforaphaneinduces cell type-specific apoptosis in human breastcancer 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 analogsof sulforaphane: correlation between structure and potency as inducersof 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) Cloneddendritic cells can present exogenous antigens on both MHC classI and class II molecules. J. Immunol. 158, 2723-2730.
  29. Sigal, L. J., Crotty, S., Andino, R. and Rock, K. L. (1999) CytotoxicT-cell immunity to virus-infected non-haematopoietic cells requirespresentation 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 initiatedby 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 pulmonarymetastasis in TRAMP mice in association with increasedcytotoxicity 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 celland antibody-dependent cellular cytotoxicity in BALB/c mice bysulforaphane, a naturally occurring isothiocyanate from broccolithrough 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 ofSulforaphane, 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 vanden Brandt, P. A. (1996) Epidemiological studies on brassica vegetablesand cancer risk. Cancer Epidemiol. Biomarkers Prev. 5,733-748.
  36. Yang, C. S., Smith, T. J. and Hong, J. Y. (1994) Cytochrome P-450enzymes as targets for chemoprevention against chemical carcinogenesisand 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 structurallyrelated 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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