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http://dx.doi.org/10.4110/in.2014.14.6.328

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)
Publication Information
IMMUNE NETWORK / v.14, no.6, 2014 , pp. 328-332 More about this Journal
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.
Keywords
Dexamethasone; MHC-restricted antigen processing; Macrophage;
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1 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.   DOI   ScienceOn
2 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.   DOI
3 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.   DOI
4 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.   DOI
5 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.   DOI
6 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.   DOI
7 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.   DOI
8 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.
9 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.   DOI
10 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.   DOI   ScienceOn
11 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.
12 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.   DOI   ScienceOn
13 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.   DOI
14 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.   DOI
15 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.   DOI
16 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.   DOI
17 Culpepper, J. A., and F. Lee. 1985. Regulation of IL 3 expression by glucocorticoids in cloned murine T lymphocytes. J. Immunol. 135: 3191-3197.
18 Marx, J. 1995. How the glucocorticoids suppress immunity. Science 270: 232-233.   DOI
19 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.   DOI
20 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.
21 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.   DOI
22 Furue, M., and Y. Ishibashi. 1991. Differential regulation by dexamethasone and cyclosporine of human T cells activated by various stimuli. Transplantation 52: 522-526.   DOI
23 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.   DOI   ScienceOn
24 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.
25 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.   DOI