DOI QR코드

DOI QR Code

IL-4 and HDAC Inhibitors Suppress Cyclooxygenase-2 Expression in Human Follicular Dendritic Cells

  • Cho, Whajung (Department of Microbiology and Immunology, School of Medicine, Kangwon National University) ;
  • Hong, Seung Hee (Department of Food Nutritional Sciences, Hanbuk University) ;
  • Choe, Jongseon (Department of Microbiology and Immunology, School of Medicine, Kangwon National University)
  • Received : 2013.03.07
  • Accepted : 2013.03.27
  • Published : 2013.04.30

Abstract

Evidence for immunoregulatory roles of prostaglandins (PGs) is accumulating. Since our observation of PG production by human follicular dendritic cells (FDCs), we investigated the regulatory mechanism of PG production in FDC and attempted to understand the functions of released PGs in the responses of adjacent lymphocytes. Here, using FDC-like cells, HK cells, we analyzed protein expression alterations in cyclooxygenase-2 (COX-2) in the presence of IL-4 or histone deacetylase (HDAC) inhibitors. Both IL-4 and HDAC inhibitors suppressed COX-2 expression in dose-dependent manners. Their effect was specific to COX-2 and did not reach to COX-1 expression. Interestingly, HDAC inhibitors gave rise to an opposing effect on COX-2 expression in peripheral blood monocytes. Our results suggest that IL-4 may regulate COX-2 expression in FDCs by affecting chromatin remodeling and provide insight into the role of cellular interactions between T cells and FDC during the GC reaction. Given the growing interests in wide-spectrum HDAC inhibitors, the differential results on COX-2 expression in HK cells and monocytes raise cautions on their clinical use.

Keywords

References

  1. Deshane, J. and D. D. Chaplin. 2010. Follicular dendritic cell makes environmental sense. Immunity 33: 2-4. https://doi.org/10.1016/j.immuni.2010.07.008
  2. Lindhout, E., M. van Eijk, M. van Pel, J. Lindeman, H. J. Dinant, and C. de Groot. 1999. Fibroblast-like synoviocytes from rheumatoid arthritis patients have intrinsic properties of follicular dendritic cells. J. Immunol. 162: 5949-5956.
  3. Fakher, M., J. Wu, D. Qin, A. Szakal, and J. Tew. 2001. Follicular dendritic cell accessory activity crosses MHC and species barriers. Eur. J. Immunol. 31: 176-185. https://doi.org/10.1002/1521-4141(200101)31:1<176::AID-IMMU176>3.0.CO;2-H
  4. Lee, I. Y., W. Cho, J. Kim, C. S. Park, and J. Choe. 2008. Human follicular dendritic cells interact with T cells via expression and regulation of cyclooxygenases and prostaglandin E and I synthases. J. Immunol. 180: 1390-1397.
  5. Kim, H. S., X. Zhang, and Y. S. Choi. 1994. Activation and proliferation of follicular dendritic cell-like cells by activated T lymphocytes. J. Immunol. 153: 2951-2961.
  6. Lee, I. Y., E. M. Ko, S. H. Kim, D. I. Jeoung, and J. Choe. 2005. Human follicular dendritic cells express prostacyclin synthase: a novel mechanism to control T cell numbers in the germinal center. J. Immunol. 175: 1658-1664. https://doi.org/10.4049/jimmunol.175.3.1658
  7. Kim, J., C. S. Park, C. H. Park, D. I. Jeoung, Y. M. Kim, and J. Choe. 2011. Beraprost enhances the APC function of B cells by upregulating CD86 expression levels. J. Immunol. 186: 3866-3873. https://doi.org/10.4049/jimmunol.1002170
  8. Kalinski, P. 2012. Regulation of immune responses by prostaglandin E2. J. Immunol. 188: 21-28. https://doi.org/10.4049/jimmunol.1101029
  9. Cho, W., J. Kim, K. B. Cho, and J. Choe. 2011. Production of prostaglandin e(2) and i(2) is coupled with cyclooxygenase- 2 in human follicular dendritic cells. Immune Netw. 11: 364-367. https://doi.org/10.4110/in.2011.11.6.364
  10. Butch, A. W., G. H. Chung, J. W. Hoffmann, and M. H. Nahm. 1993. Cytokine expression by germinal center cells. J. Immunol. 150: 39-47.
  11. Cao, D., P. A. Bromberg, and J. M. Samet. 2007. COX-2 expression induced by diesel particles involves chromatin modification and degradation of HDAC1. Am. J. Respir. Cell Mol. Biol. 37: 232-239. https://doi.org/10.1165/rcmb.2006-0449OC
  12. Pero, R., S. Peluso, T. Angrisano, C. Tuccillo, S. Sacchetti, S. Keller, R. Tomaiuolo, C. B. Bruni, F. Lembo, and L. Chiariotti. 2011. Chromatin and DNA methylation dynamics of Helicobacter pylori-induced COX-2 activation. Int. J. Med. Microbiol. 301: 140-149. https://doi.org/10.1016/j.ijmm.2010.06.009
  13. Hsu, Y. F., J. R. Sheu, C. H. Lin, W. C. Chen, G. Hsiao, G. Ou, P. T. Chiu, and M. J. Hsu. 2011. MAPK phosphatase-1 contributes to trichostatin A inhibition of cyclooxygenase-2 expression in human umbilical vascular endothelial cells exposed to lipopolysaccharide. Biochim. Biophys. Acta 1810: 1160-1169. https://doi.org/10.1016/j.bbagen.2011.08.015
  14. Cho, W., Y. Kim, D. I. Jeoung, Y. M. Kim, and J. Choe. 2011. IL-4 and IL-13 suppress prostaglandins production in human follicular dendritic cells by repressing COX-2 and mPGES-1 expression through JAK1 and STAT6. Mol. Immunol. 48: 966-972. https://doi.org/10.1016/j.molimm.2011.01.007
  15. Lee, I. Y., Y. D. Bae, D. I. Jeoung, D. Kang, C. H. Park, S. H. Kim, and J. Choe. 2007. Prostacyclin production is not controlled by prostacyclin synthase but by cyclooxygenase-2 in a human follicular dendritic cell line, HK. Mol. Immunol. 44: 3168-3172. https://doi.org/10.1016/j.molimm.2007.01.025
  16. Kim, J., Y. M. Kim, D. I. Jeoung, and J. Choe. 2012. Human follicular dendritic cells promote the APC capability of B cells by enhancing CD86 expression levels. Cell. Immunol. 273: 109-114. https://doi.org/10.1016/j.cellimm.2012.01.003
  17. Marinova, E., S. Han, and B. Zheng. 2007. Germinal center helper T cells are dual functional regulatory cells with suppressive activity to conventional CD4+ T cells. J. Immunol. 178: 5010-5017. https://doi.org/10.4049/jimmunol.178.8.5010
  18. Wollenberg, I., A. Agua-Doce, A. Hernández, C. Almeida, V. G. Oliveira, J. Faro, and L. Graca. 2011. Regulation of the germinal center reaction by Foxp3+ follicular regulatory T cells. J. Immunol. 187: 4553-4560. https://doi.org/10.4049/jimmunol.1101328
  19. Chung, Y., S. Tanaka, F. Chu, R. I. Nurieva, G. J. Martinez, S. Rawal, Y. H. Wang, H. Lim, J. M. Reynolds, X. H. Zhou, H. M. Fan, Z. M. Liu, S. S. Neelapu, and C. Dong. 2011. Follicular regulatory T cells expressing Foxp3 and Bcl-6 suppress germinal center reactions. Nat. Med. 17: 983-988. https://doi.org/10.1038/nm.2426
  20. Alaaeddine, N., J. A. Di Battista, J. P. Pelletier, K. Kiansa, J. M. Cloutier, and J. Martel-Pelletier. 1999. Inhibition of tumor necrosis factor alpha-induced prostaglandin E2 production by the antiinflammatory cytokines interleukin-4, interleukin- 10, and interleukin-13 in osteoarthritic synovial fibroblasts: distinct targeting in the signaling pathways. Arthritis. Rheum. 42: 710-718. https://doi.org/10.1002/1529-0131(199904)42:4<710::AID-ANR14>3.0.CO;2-4
  21. Halili, M. A., M. R. Andrews, L. I. Labzin, K. Schroder, G. Matthias, C. Cao, E. Lovelace, R. C. Reid, G. T. Le, D. A. Hume, K. M. Irvine, P. Matthias, D. P. Fairlie, and M. J. Sweet. 2010. Differential effects of selective HDAC inhibitors on macrophage inflammatory responses to the Toll-like receptor 4 agonist LPS. J. Leukoc. Biol. 87: 1103-1114. https://doi.org/10.1189/jlb.0509363
  22. Munoz-Fernandez, R., F. J. Blanco, C. Frecha, F. Martín, M. Kimatrai, A. C. Abadia-Molina, J. M. Garcia-Pacheco, and E. G. Olivares. 2006. Follicular dendritic cells are related to bone marrow stromal cell progenitors and to myofibroblasts. J. Immunol. 177: 280-289.