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The Role of Transglutaminase in Double-stranded DNA-Triggered Antiviral Innate Immune Response

  • Yoo, Jae-Wook (Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University) ;
  • Hong, Sun-Woo (Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University) ;
  • Bose, Shambhunath (Institute of Medical Research, College of Medicine, Dongguk University) ;
  • Kim, Ho-Jun (Institute of Medical Research, College of Medicine, Dongguk University) ;
  • Kim, Soo-Youl (Cancer Cell and Molecular Biology Branch, Division of Cancer Biology, Research Institute) ;
  • Kim, So-Youn (Department of Biomedical Engineering, Dongguk University) ;
  • Lee, Dong-Ki (Global Research Laboratory for RNAi Medicine, Department of Chemistry, Sungkyunkwan University)
  • Received : 2011.08.26
  • Accepted : 2011.09.02
  • Published : 2011.11.20

Abstract

Cellular uptake of double-stranded DNA (dsDNA) triggers strong innate immune responses via activation of NF-${\kappa}B$ transcription factor. However, the detailed mechanism of dsDNA-mediated innate immune response remains yet to be elucidated. Here, we show that the expression of tazarotene-induced gene 3 (TIG3) is dramatically induced by dsDNA stimulation, and the siRNA-mediated down-regulation of TIG3 mRNA results in significant suppression of dsDNA-triggered cytokine expression. Because TIG3 has been previously shown to physically interact with transglutaminase (TG) 1 to activate TG activity, and TG2 has been shown to induce NF-${\kappa}B$ activity by inducing $I{\kappa}B{\alpha}$ polymerization, we tested whether TG also plays a role in dsDNA-mediated innate immune response. Pre-treatment of TG inhibitors dramatically reduces dsDNA-triggered cytokine induction. We also show that, in HeLa cells, TG2 is the major TG, and TIG3 physically interacts with TG2. Combined together, our results suggest a novel mechanism of dsDNA-triggered innate immune response which is critically dependent on TIG3 and TG2.

Keywords

References

  1. Barbalat, R.; Ewald, S. E.; Mouchess, M. L.; Barton, G. M. Annu. Rev. Immunol. 2011, 29, 185-214. https://doi.org/10.1146/annurev-immunol-031210-101340
  2. Kawai, T.; Akira, S. Immunity 2011, 34, 637-650. https://doi.org/10.1016/j.immuni.2011.05.006
  3. Kumar, H.; Kawai, T.; Akira, S. Int. Rev. Immunol. 2011, 30, 16- 34. https://doi.org/10.3109/08830185.2010.529976
  4. Loo, Y. M.; Gale, M., Jr. Immunity 2011, 34, 680-692. https://doi.org/10.1016/j.immuni.2011.05.003
  5. Onomoto, K.; Onoguchi, K.; Takahasi, K.; Fujita, T. J. Interferon Cytokine Res. 2010, 30, 875-881. https://doi.org/10.1089/jir.2010.0117
  6. Yoneyama, M.; Fujita, T. Immunol. Rev. 2009, 227, 54-65. https://doi.org/10.1111/j.1600-065X.2008.00727.x
  7. Wang, Z.; Choi, M. K.; Ban, T.; Yanai, H.; Negishi, H.; Lu, Y.; Tamura, T.; Takaoka, A.; Nishikura, K.; Taniguchi, T. Proc. Natl. Acad Sci. U S A 2008, 105, 5477-5482. https://doi.org/10.1073/pnas.0801295105
  8. Ha, S. C.; Kim, D.; Hwang, H. Y.; Rich, A.; Kim, Y. G.; Kim, K. K. Proc. Natl. Acad Sci. U S A 2008, 105, 20671-20676. https://doi.org/10.1073/pnas.0810463106
  9. Chi, H.; Flavell, R. A. Nature 2007, 448, 423-424. https://doi.org/10.1038/448423a
  10. Rebsamen, M.; Heinz, L. X.; Meylan, E.; Michallet, M. C.; Schroder, K.; Hofmann, K.; Vazquez, J.; Benedict, C. A.; Tschopp, J. EMBO Rep. 2009, 10, 916-922. https://doi.org/10.1038/embor.2009.109
  11. Kaiser, W. J.; Upton, J. W.; Mocarski, E. S. J. Immunol. 2008, 181, 6427-6434. https://doi.org/10.4049/jimmunol.181.9.6427
  12. Burckstummer, T.; Baumann, C.; Bluml, S.; Dixit, E.; Durnberger, G.; Jahn, H.; Planyavsky, M.; Bilban, M.; Colinge, J.; Bennett, K. L.; Superti-Furga, G. Nat. Immunol. 2009, 10, 266-272. https://doi.org/10.1038/ni.1702
  13. Fernandes-Alnemri, T.; Yu, J. W.; Datta, P.; Wu, J.; Alnemri, E. S. Nature 2009, 458, 509-513. https://doi.org/10.1038/nature07710
  14. Hornung, V.; Ablasser, A.; Charrel-Dennis, M.; Bauernfeind, F.; Horvath, G.; Caffrey, D. R.; Latz, E.; Fitzgerald, K. A. Nature 2009, 458, 514-518. https://doi.org/10.1038/nature07725
  15. Roberts, T. L.; Idris, A.; Dunn, J. A.; Kelly, G. M.; Burnton, C. M.; Hodgson, S.; Hardy, L. L.; Garceau, V.; Sweet, M. J.; Ross, I. L.; Hume, D. A.; Stacey, K. J. Science 2009, 323, 1057-1060. https://doi.org/10.1126/science.1169841
  16. Pisano, J. J.; Finlayson, J. S.; Peyton, M. P. Science 1968, 160, 892-893. https://doi.org/10.1126/science.160.3830.892
  17. Griffin, M.; Casadio, R.; Bergamini, C. M. Biochem. J. 2002, 368, 377-396. https://doi.org/10.1042/BJ20021234
  18. Folk, J. E.; Chung, S. I. Methods Enzymol. 1985, 113, 358-375. https://doi.org/10.1016/S0076-6879(85)13049-1
  19. Martinet, N.; Beninati, S.; Nigra, T. P.; Folk, J. E. Biochem. J. 1990, 271, 305-308.
  20. Grenard, P.; Bates, M. K.; Aeschlimann, D. J. Biol. Chem. 2001, 276, 33066-33078. https://doi.org/10.1074/jbc.M102553200
  21. Lorand, L.; Graham, R. M. Nat. Rev. Mol. Cell Biol. 2003, 4, 140- 156. https://doi.org/10.1038/nrm1014
  22. Chen, J. S.; Mehta, K. Int. J. Biochem. Cell Biol. 1999, 31, 817- 836. https://doi.org/10.1016/S1357-2725(99)00045-X
  23. Sohn, J.; Kim, T. I.; Yoon, Y. H.; Kim, J. Y.; Kim, S. Y. J. Clin. Invest. 2003, 111, 121-128. https://doi.org/10.1172/JCI200315937
  24. Choi, Y. C.; Park, G. T.; Kim, T. S.; Sunwoo, I. N.; Steinert, P. M.; Kim, S. Y. J. Biol. Chem. 2000, 275, 8703-8710. https://doi.org/10.1074/jbc.275.12.8703
  25. Choi, Y. C.; Kim, T. S.; Kim, S. Y. Eur. Neurol. 2004, 51, 10-14. https://doi.org/10.1159/000074911
  26. Lee, J.; Kim, Y. S.; Choi, D. H.; Bang, M. S.; Han, T. R.; Joh, T. H.; Kim, S. Y. J. Biol. Chem. 2004, 279, 53725-53735. https://doi.org/10.1074/jbc.M407627200
  27. Rice, R. H.; Green, H. Cell 1977, 11, 417-422. https://doi.org/10.1016/0092-8674(77)90059-9
  28. Eckert, R. L. Physiol. Rev. 1989, 69, 1316-1346.
  29. Sturniolo, M. T.; Dashti, S. R.; Deucher, A.; Rorke, E. A.; Broome, A. M.; Chandraratna, R. A.; Keepers, T.; Eckert, R. L. J. Biol. Chem. 2003, 278, 48066-48073. https://doi.org/10.1074/jbc.M307215200
  30. Sturniolo, M. T.; Chandraratna, R. A.; Eckert, R. L. Oncogene 2005, 24, 2963-2972. https://doi.org/10.1038/sj.onc.1208392
  31. DiSepio, D.; Ghosn, C.; Eckert, R. L.; Deucher, A.; Robinson, N.; Duvic, M.; Chandraratna, R. A.; Nagpal, S. Proc. Natl. Acad Sci. U S A 1998, 95, 14811-14815. https://doi.org/10.1073/pnas.95.25.14811
  32. Deucher, A.; Nagpal, S.; Chandraratna, R. A.; Di Sepio, D.; Robinson, N. A.; Dashti, S. R.; Eckert, R. L. Int. J. Oncol. 2000, 17, 1195-1203.
  33. Tsai, F. M.; Shyu, R. Y.; Jiang, S. Y. Cell Signal 2007, 19, 989- 999. https://doi.org/10.1016/j.cellsig.2006.11.005
  34. Park, S. S.; Kim, J. M.; Kim, D. S.; Kim, I. H.; Kim, S. Y. J. Biol. Chem. 2006, 281, 34965-34972. https://doi.org/10.1074/jbc.M604150200
  35. Mann, A. P.; Verma, A.; Sethi, G.; Manavathi, B.; Wang, H.; Fok, J. Y.; Kunnumakkara, A. B.; Kumar, R.; Aggarwal, B. B.; Mehta, K. Cancer. Res. 2006, 66, 8788-8795. https://doi.org/10.1158/0008-5472.CAN-06-1457
  36. Kim, D. S.; Park, S. S.; Nam, B. H.; Kim, I. H.; Kim, S. Y. Cancer. Res. 2006, 66, 10936-10943. https://doi.org/10.1158/0008-5472.CAN-06-1521
  37. Condello, S.; Caccamo, D.; Curro, M.; Ferlazzo, N.; Parisi, G.; Ientile, R. Brain. Res. 2008, 1207, 1-8. https://doi.org/10.1016/j.brainres.2008.02.044
  38. Jans, R.; Sturniolo, M. T.; Eckert, R. L. J. Invest. Dermatol. 2008, 128, 517-529.
  39. Kim, D. S.; Kim, B.; Tahk, H.; Kim, D. H.; Ahn, E. R.; Choi, C.; Jeon, Y.; Park, S. Y.; Lee, H.; Oh, S. H.; Kim, S. Y. Biochem. Biophys. Res. Commun. 2010, 403, 479-484. https://doi.org/10.1016/j.bbrc.2010.11.063
  40. Kim, D. Y.; Park, B. S.; Hong, G. U.; Lee, B. J.; Park, J. W.; Kim, S. Y.; Ro, J. Y. Br. J. Pharmacol. 2011, 162, 210-225. https://doi.org/10.1111/j.1476-5381.2010.01033.x
  41. Kim, J. M.; Voll, R. E.; Ko, C.; Kim, D. S.; Park, K. S.; Kim, S. Y. J. Mol. Biol. 2008, 384, 756-765. https://doi.org/10.1016/j.jmb.2008.10.010