Regulation of HMGB1 release by inflammasomes

Abstract

High mobility group box 1 (HMGB1) is an evolutionarily conserved non-histone chromatin-binding protein. During infection or injury, activated immune cells and damaged cells release HMGB1 into the extracellular space, where HMGB1 functions as a proinflammatory mediator and contributes importantly to the pathogenesis of infl ammatory diseases. Recent studies reveal that inflammasomes, intracellular protein complexes, critically regulate HMGB1 release from activated immune cells in response to a variety of exogenous and endogenous danger signals. Double stranded RNA dependent kinase (PKR), an intracellular danger-sensing molecule, physically interacts with inflammasome components and is important for inflammasome activation and HMGB1 release. Together, these studies not only unravel novel mechanisms of HMGB1 release during infl ammation, but also provide potential therapeutic targets to treat HMGB1-related infl ammatory diseases.

Key words： HMGB1; inflammasome; PKR

References

[1] Andersson, U., and Tracey, K.J. (2011). HMGB1 is a therapeutic target for sterile infl ammation and infection. Annu Rev Immunol 29, 139-162 .10.1146/annurev-immunol-030409-101323
[2] Bonaldi, T., Talamo, F., Scaffidi, P., Ferrera, D., Porto, A., Bachi, A., Rubartelli, A., Agresti, A., and Bianchi, M.E. (2003). Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 22, 5551-5560 .10.1093/emboj/cdg516
[3] Bustin, M., and Neihart, N.K. (1979). Antibodies against chromosomal HMG proteins stain the cytoplasm of mammalian cells. Cell 16, 181-189 .10.1016/0092-8674(79)90199-5
[4] Dey, M., Cao, C., Dar, A.C., Tamura, T., Ozato, K., Sicheri, F., and Dever, T.E. (2005). Mechanistic link between PKR dimerization, autophosphorylation, and eIF2alpha substrate recognition. Cell 122, 901-913 .10.1016/j.cell.2005.06.041
[5] Evankovich, J., Cho,SW., Zhang, R., Cardinal, J., Dhupar, R., Zhang, L., Klune, J.R., Zlotnicki, J., Billiar, T., and Tsung, A. (2010). High mobility group box 1 release from hepatocytes during ischemia and reperfusion injury is mediated by decreased histone deacetylase activity. J Biol Chem . 285, 39888-39897 .10.1074/jbc.M110.128348
[6] Franchi, L., Mu?oz-Planillo, R., and Nú?ez, G. (2012) Sensing and reacting to microbes through the inflammasomes. Nat Immunol 13, 325-332 .10.1038/ni.2231
[7] Gardella, S., Andrei, C., Ferrera, D., Lotti, L.V., Torrisi, M.R., Bianchi, M.E., and Rubartelli, A. (2002). The nuclear protein HMGB1 is secreted by monocytes via a non-classical, vesicle-mediated secretory pathway. EMBO Rep 3, 995-1001 .10.1093/embo-reports/kvf198
[8] Hsu, L.C., Park, J.M., Zhang, K., Luo, J.L., Maeda, S., Kaufman, R.J., Eckmann, L., Guiney, D.G., and Karin, M. (2004). The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428, 341-345 .10.1038/nature02405
[9] Javaherian, K., Liu, J.F., and Wang, J.C. (1978). Nonhistone proteins HMGB1 release. Nature 488, 670-674 .
[10] Manfredi, A.A., Capobianco, A., Esposito, A., De Cobelli, F., Canu, T., Monno, A., Raucci, A., Sanvito, F., Doglioni, C., Nawroth, P.P., . (2008). Maturing dendritic cells depend on RAGE for in vivo homing to lymph nodes. J Immunol 180, 2270-2275 .
[11] Maroso, M., Balosso, S., Ravizza, T., Liu, J., Aronica, E., Iyer, A.M., Rossetti, C., Molteni, M., Casalgrandi, M., Manfredi, A.A., . (2010). Toll-like receptor 4 and high-mobility group box-1 are involved in ictogenesis and can be targeted to reduce seizures. Nat Med 16, 413-419 .10.1038/nm.2127
[12] Medzhitov, R. (2010). Infl ammation 2010: new adventures of an old fl ame. Cell 140, 771-776 .10.1016/j.cell.2010.03.006
[13] Miao, E.A., Rajan, J.V., and Aderem, A. (2011). Caspase-1-induced pyroptotic cell death. Immunol Rev 243, 206-214 .10.1111/j.1600-065X.2011.01044.x
[14] Müller, S., Scaffidi, P., Degryse, B., Bonaldi, T., Ronfani, L., Agresti, A., Beltrame, M., and Bianchi, M.E. (2001). New EMBO members’ review: the double life of HMGB1 chromatin protein: architectural factor and extracellular signal. EMBO J 20, 4337-4340 .10.1093/emboj/20.16.4337
[15] Nakamura, T., Furuhashi, M., Li, P., Cao, H., Tuncman, G., Sonenberg, N., Gorgun, C.Z., and Hotamisligil, G.S. (2010). Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. Cell 140, 338-348 .10.1016/j.cell.2010.01.001
[16] Qin, S., Wang, H., Yuan, R., Li, H., Ochani, M., Ochani, K., Rosas- Ballina, M., Czura, C.J., Huston, J.M., Miller, E., . (2006). Role of HMGB1 in apoptosis-mediated sepsis lethality. J Exp Med 203, 1637-1642 .10.1084/jem.20052203
[17] Rathinam, V.A., Vanaja, S.K., and Fitzgerald, K.A. (2012). Regulation of inflammasome signaling. Nat Immunol 13, 333-332 .10.1038/ni.2237
[18] Scaffi di, P., Misteli, T., and Bianchi, M.E. (2002). Release of chromatin protein HMGB1 by necrotic cells triggers infl ammation. Nature 418, 191-195 .10.1038/nature00858
[19] Schiraldi, M., Raucci, A., Mu?oz, L.M., Livoti, E., Celona, B., Venereau, E., Apuzzo, T., De Marchis, F., Pedotti, M., Bachi, A., . (2012). HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4. J Exp Med 209, 551-563 .10.1084/jem.20111739
[20] Strowig, T., Henao-Mejia, J., Elinav, E., and Flavell, R. (2012). inflammasomes in health and disease. Nature 481, 278-286 .10.1038/nature10759
[21] Wang, H., Bloom, O., Zhang, M., Vishnubhakat, J.M., Ombrellino, M., Che, J., Frazier, A., Yang, H., Ivanova, S., Borovikova, L., . (1999). HMG-1 as a late mediator of endotoxin lethality in mice. Science 285, 248-251 .10.1126/science.285.5425.248
[22] Wen, H., Ting, J.P., and O’Neill, L.A. (2012). A role for the NLRP3 inflammasome in metabolic diseases--did Warburg miss infl ammation. Nat Immunol 13, 352-357 .10.1038/ni.2228
[23] Willingham, S.B., Allen, I.C., Bergstralh, D.T., Brickey, W.J., Huang, M.T., Taxman, D.J., Duncan, J.A., and Ting, J.P. (2009). NLRP3 (NALP3, Cryopyrin) facilitates in vivo caspase-1 activation, necrosis, and HMGB1 release via inflammasome-dependent and-independent pathways. J Immunol 182, 6460-6469 .
[24] Topalova, D., Ugrinova, I., Pashev, I.G., and Pasheva, E.A. (2008). HMGB1 protein inhibits DNA replication in vitro: a role of the acetylation and the acidic tail. Int J Biochem Cell Biol 40, 1536-1542 .10.1016/j.biocel.2007.11.014
[25] Venereau, E., Casalgrandi, M., Schiraldi, M., Antoine, D.J., Cattaneo, A., De Marchis, F., Liu, J., Antonelli, A., Preti, A., Raeli, L., . (2012). Mutually exclusive redox forms of HMGB1 promote cell recruitment or proinfl ammatory cytokine release. J Exp Med 209, 1519-1528 .10.1084/jem.20120189
[26] Yang, H., Hreggvidsdottir, H.S., Palmblad, K., Wang, H., Ochani, M., Li, J., Lu, B., Chavan, S., Rosas-Ballina, M., Al-Abed, Y., . (2010). A critical cysteine is required for HMGB1 binding to Toll-like receptor 4 and activation of macrophage cytokine release. Proc Natl Acad Sci U S A 107, 11942-11947 .10.1073/pnas.1003893107
[27] Zhao, Y., Yang, J., Shi, J., Gong, Y.N., Lu, Q., Xu, H., Liu, L., and Shao, F. (2011). The NLRC4 inflammasome receptors for bacterial fl agellin and type III secretion apparatus. Nature 477, 596-600 .10.1038/nature10510