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Evidence for Direct Inhibition of MHC-Restricted Antigen Processing by Dexamethasone

  • Im, Sun-A (College of Pharmacy, Chungbuk National University) ;
  • Gerelchuluun, Turmunkh (Department of Biotechnology and Nutrition School of Industrial Technology, Mongolian University of Science and Technology) ;
  • Lee, Chong-Kil (College of Pharmacy, Chungbuk National University)
  • Received : 2014.10.13
  • Accepted : 2014.12.05
  • Published : 2014.12.31
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Abstract

Dexamethasone (Dex) was shown to inhibit the differentiation, maturation, and antigen-presenting function of dendritic cells (DC) when added during DC generation or maturation stages. Here, we examined the direct effects of Dex on MHC-restricted antigen processing. Macrophages were incubated with microencapsulated ovalbumin (OVA) in the presence of different concentrations of Dex for 2 h, and the efficacy of OVA peptide presentation was evaluated using OVA-specific CD8 and CD4 T cells. Dex inhibited both class I- and class II-restricted presentation of OVA to T cells; this inhibitory effect on antigen presentation was much more potent in immature macrophages than in mature macrophages. The presentation of the exogenously added OVA peptide SIINFEKL was not blocked by Dex. In addition, short-term treatment of macrophages with Dex had no discernible effects on the phagocytic activity, total expression levels of MHC molecules or co-stimulatory molecules. These results demonstrate that Dex inhibits intracellular processing events of phagocytosed antigens in macrophages.

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References

  1. Boumpas, D. T., F. Paliogianni, E. D. Anastassiou, and J. E. Balow. 1991. Glucocorticosteroid action on the immune system: molecular and cellular aspects. Clin. Exp. Rheumatol. 9: 413-423.
  2. Marx, J. 1995. How the glucocorticoids suppress immunity. Science 270: 232-233. https://doi.org/10.1126/science.270.5234.232
  3. Kitajima, T., K. Ariizumi, P. R. Bergstresser, and A. Takashima. 1996. A novel mechanism of glucocorticoid-induced immune suppression: the inhibiton of T cell-mediated terminal maturation of a murine dendritic cell line. J. Clin. Invest. 98: 142-147. https://doi.org/10.1172/JCI118759
  4. Arya, S. K., F. Wong-Staal, and R. C. Gallo. 1984. Dexamethasone-mediated inhibition of human T cell growth factor and gamma-interferon messenger RNA. J. Immunol. 133: 273-276.
  5. Culpepper, J. A., and F. Lee. 1985. Regulation of IL 3 expression by glucocorticoids in cloned murine T lymphocytes. J. Immunol. 135: 3191-3197.
  6. Wu, C. Y., C. Fargeas, T. Nakajima, and G. Delespesse. 1991. Glucocorticoids suppress the production of interleukin 4 by human lymphocytes. Eur. J. Immunol. 21: 2645-2647. https://doi.org/10.1002/eji.1830211053
  7. Furue, M., and Y. Ishibashi. 1991. Differential regulation by dexamethasone and cyclosporine of human T cells activated by various stimuli. Transplantation 52: 522-526. https://doi.org/10.1097/00007890-199109000-00027
  8. Waage, A., G. Slupphaug, and R. Shalaby. 1990. Glucocorticoids inhibit the production of IL6 from monocytes, endothelial cells and fibroblasts. Eur. J. Immunol. 20: 2439-2443. https://doi.org/10.1002/eji.1830201112
  9. Heidenreich, S., T. Kubis, M. Schmidt, and W. Fegeler. 1994. Glucocorticoid-induced alterations of monocyte defense mechanisms against Candida albicans. Cell Immunol. 157: 320-327. https://doi.org/10.1006/cimm.1994.1230
  10. Almawi, W. Y., H. N. Beyhum, A. A. Rahme, and M. J. Rieder. 1996. Regulation of cytokine and cytokine receptor expression by glucocorticoids. J. Leukoc. Biol. 60: 563-572. https://doi.org/10.1002/jlb.60.5.563
  11. Fushimi, T., H. Okayama, T. Seki, S. Shimura, and K. Shirato. 1997. Dexamethasone suppressed gene expression and production of interleukin-10 by human peripheral blood mononuclear cells and monocytes. Int. Arch. Allergy Immunol. 112: 13-18. https://doi.org/10.1159/000237425
  12. Chen, X., J. J. Oppenheim, R. T. Winkler-Pickett, J. R. Ortaldo, and O. M. Howard. 2006. Glucocorticoid amplifies IL-2-dependent expansion of functional FoxP3(+)CD4(+) CD25(+) T regulatory cells in vivo and enhances their capacity to suppress EAE. Eur. J. Immunol. 36: 2139-2149. https://doi.org/10.1002/eji.200635873
  13. Chen, X., T. Murakami, J. J. Oppenheim, and O. M. Howard. 2004. Differential response of murine $CD4^+CD25^+$ and $CD4^+CD25^-$ T cells to dexamethasone-induced cell death. Eur. J. Immunol. 34: 859-869. https://doi.org/10.1002/eji.200324506
  14. Zheng, G., S. Zhong, Y. Geng, G. Munirathinam, I. Cha, C. Reardon, G. S. Getz, R. N. van, Y. Kang, B. Wang, and A. Chen. 2013. Dexamethasone promotes tolerance in vivo by enriching $CD11c^{lo}$ $CD40c^{lo}$ tolerogenic macrophages. Eur. J. Immunol. 43: 219-227. https://doi.org/10.1002/eji.201242468
  15. Rozkova, D., R. Horvath, J. Bartunkova, and R. Spisek. 2006. Glucocorticoids severely impair differentiation and antigen presenting function of dendritic cells despite upregulation of Toll-like receptors. Clin. Immunol. 120: 260-271. https://doi.org/10.1016/j.clim.2006.04.567
  16. Piemonti, L., P. Monti, P. Allavena, M. Sironi, L. Soldini, B. E. Leone, C. Socci, and C. Di, V. 1999. Glucocorticoids affect human dendritic cell differentiation and maturation. J. Immunol. 162: 6473-6481.
  17. Pan, J., D. Ju, Q. Wang, M. Zhang, D. Xia, L. Zhang, H. Yu, and X. Cao. 2001. Dexamethasone inhibits the antigen presentation of dendritic cells in MHC class II pathway. Immunol. Lett. 76: 153-161. https://doi.org/10.1016/S0165-2478(01)00183-3
  18. Karttunen, J., S. Sanderson, and N. Shastri. 1992. Detection of rare antigen-presenting cells by the lacZ T-cell activation assay suggests an expression cloning strategy for T-cell antigens. Proc. Natl. Acad. Sci. U. S. A. 89: 6020-6024. https://doi.org/10.1073/pnas.89.13.6020
  19. Harding, C. V., and R. Song. 1994. Phagocytic processing of exogenous particulate antigens by macrophages for presentation by class I MHC molecules. J. Immunol. 153: 4925-4933.
  20. Lee, Y. R., Y. H. Lee, S. A. Im, I. H. Yang, G. W. Ahn, K. Kim, and C. K. Lee. 2010. Biodegradable nanoparticles containing TLR3 or TLR9 agonists together with antigen enhance MHC-restricted presentation of the antigen. Arch. Pharm. Res. 33: 1859-1866. https://doi.org/10.1007/s12272-010-1119-z
  21. Lee, Y. R., I. H. Yang, Y. H. Lee, S. A. Im, S. Song, H. Li, K. Han, K. Kim, S. K. Eo, and C. K. Lee. 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
  22. Matyszak, M. K., S. Citterio, M. Rescigno, and P. Ricciardi-Castagnoli. 2000. Differential effects of corticosteroids during different stages of dendritic cell maturation. Eur. J. Immunol. 30: 1233-1242. https://doi.org/10.1002/(SICI)1521-4141(200004)30:4<1233::AID-IMMU1233>3.0.CO;2-F
  23. Woltman, A. M., J. W. de Fijter, S. W. Kamerling, L. C. Paul, M. R. Daha, and K. C. van. 2000. The effect of calcineurin inhibitors and corticosteroids on the differentiation of human dendritic cells. Eur. J. Immunol. 30: 1807-1812. https://doi.org/10.1002/1521-4141(200007)30:7<1807::AID-IMMU1807>3.0.CO;2-N
  24. Orlikowsky, T. W., G. E. Dannecker, B. Spring, M. Eichner, M. K. Hoffmann, and C. F. Poets. 2005. Effect of dexamethasone on B7 regulation and T cell activation in neonates and adults. Pediatr. Res. 57: 656-661. https://doi.org/10.1203/01.PDR.0000156211.48307.F5
  25. Salgado, C. G., K. Nakamura, M. Sugaya, Y. Tada, A. Asahina, S. Fukuda, Y. Koyama, S. Irie, and K. Tamaki. 1999. Differential effects of cytokines and immunosuppressive drugs on CD40, B7-1, and B7-2 expression on purified epidermal Langerhans cells1. J. Invest. Dermatol. 113: 1021-1027. https://doi.org/10.1046/j.1523-1747.1999.00785.x

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