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High Mobility Group Box 1: a potential therapeutic target for systemic lupus erythematosus

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Abstract

High Mobility Group Box 1 (HMGB1) is a nuclear protein participating in chromatin architecture and transcriptional regulation. Recently, there is increasing evidence that HMGB1 contributes to the pathogenesis of chronic inflammatory and autoimmune diseases due to its pro-inflammatory and immunostimulatory properties. Elevated expression of HMGB1 was found in the sera of patients and mice with systemic lupus erythematosus (SLE). In addition, it has been shown that HMGB1 may act as a proinflammatory mediator in antibody-induced kidney damage in SLE. All theses findings suggest that HMGB1 have important biological effects in autoimmunity that might be a promising therapeutic target for SLE. In this review, we will briefly discuss the biological features of HMGB1 and summarize recent advances on the role of HMGB1 in the pathogenesis and treatment of SLE.

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References

  1. Pan HF, Ye DQ, Li XP (2008) Type 17 T-helper cells might be a promising therapeutic target for systemic lupus erythematosus. Nat Clin Pract Rheumatol 4:352–353

    CAS  PubMed  Google Scholar 

  2. Pan HF, Fang XH, Li WX et al (2008) Radix astragali: a promising new treatment option for systemic lupus erythematosus. Med Hypotheses 71:311–312. doi:10.1016/j.mehy.2008.03.011

    Article  CAS  PubMed  Google Scholar 

  3. Cook HT, Botto M (2006) Mechanisms of disease: the complement system and the pathogenesis of systemic lupus erythematosus. Nat Clin Pract Rheumatol 2:330–337. doi:10.1038/ncprheum0191

    Article  CAS  PubMed  Google Scholar 

  4. Voll RE, Urbonaviciute V, Herrmann M et al (2008) High mobility group box 1 in the pathogenesis of inflammatory and autoimmune diseases. Isr Med Assoc J 10:26–28

    PubMed  Google Scholar 

  5. Jiang W, Pisetsky DS (2008) Expression of high mobility group protein 1 in the sera of patients and mice with systemic lupus erythematosus. Ann Rheum Dis 67:727–728. doi:10.1136/ard.2007.074484

    Article  CAS  PubMed  Google Scholar 

  6. Qing X, Pitashny M, Thomas DB et al (2008) Pathogenic anti-DNA antibodies modulate gene expression in mesangial cells: involvement of HMGB1 in anti-DNA antibody-induced renal injury. Immunol Lett 121:61–73. doi:10.1016/j.imlet.2008.08.007

    Article  CAS  PubMed  Google Scholar 

  7. Goodwin GH, Sanders C, Johns EW (1973) A new group of chromatin-associated proteins with a high content of acidic and basic amino acids. Eur J Biochem 38:14–19. doi:10.1111/j.1432-1033.1973.tb03026.x

    Article  CAS  PubMed  Google Scholar 

  8. Ferrari S, Finelli P, Rocchi M et al (1996) The active gene that encodes human high mobility group 1 protein (HMG1) contains introns and maps to chromosome 13. Genomics 35:367–371. doi:10.1006/geno.1996.0369

    Article  CAS  PubMed  Google Scholar 

  9. Stros M, Dixon GH (1993) A retropseudogene for non-histone chromosomal protein HMG-1. Biochim Biophys Acta 1172:231–235

    CAS  PubMed  Google Scholar 

  10. Wen L, Huang JK, Johnson BH et al (1989) A human placental cDNA clone that encodes nonhistone chromosomal protein HMG-1. Nucleic Acids Res 17:1197–1214. doi:10.1093/nar/17.3.1197

    Article  CAS  PubMed  Google Scholar 

  11. Walker JM, Gooderham K, Hastings JR et al (1980) The primary structures of non-histone chromosomal proteins HMG 1 and 2. FEBS Lett 122:264–270. doi:10.1016/0014-5793(80)80453-4

    Article  CAS  PubMed  Google Scholar 

  12. Paonessa G, Frank R, Cortese R (1987) Nucleotide sequence of rat liver HMG1 cDNA. Nucleic Acids Res 15:9077. doi:10.1093/nar/15.21.9077

    Article  CAS  PubMed  Google Scholar 

  13. Yotov WV, St-Arnaud R (1992) Nucleotide sequence of a mouse cDNA encoding the nonhistone chromosomal high mobility group protein-1 (HMG1). Nucleic Acids Res 20:3516. doi:10.1093/nar/20.13.3516

    Article  CAS  PubMed  Google Scholar 

  14. Huttunen HJ, Rauvala H (2004) Amphoterin as an extracellular regulator of cell motility: from discovery to disease. J Intern Med 255:351–366. doi:10.1111/j.1365-2796.2003.01301.x

    Article  CAS  PubMed  Google Scholar 

  15. van Beijnum JR, Buurman WA, Griffioen AW (2008) Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis 11:91–99. doi:10.1007/s10456-008-9093-5

    Article  CAS  PubMed  Google Scholar 

  16. Yang H, Wang H, Czura CJ et al (2005) The cytokine activity of HMGB1. J Leukoc Biol 78:1–8. doi:10.1189/jlb.1104648

    Article  CAS  PubMed  Google Scholar 

  17. Mosevitsky MI, Novitskaya VA, Iogannsen MG et al (1989) Tissue specificity of nucleo-cytoplasmic distribution of HMG1 and HMG2 proteins and their probable functions. Eur J Biochem 185:303–310. doi:10.1111/j.1432-1033.1989.tb15116.x

    Article  CAS  PubMed  Google Scholar 

  18. Lotze MT, Tracey KJ (2005) High-mobility group box 1 protein (HMGB1): nuclear weapon in the immune arsenal. Nat Rev Immunol 5:331–342. doi:10.1038/nri1594

    Article  CAS  PubMed  Google Scholar 

  19. Bonaldi T, Talamo F, Scaffidi P et al (2003) Monocytic cells hyperacetylate chromatin protein HMGB1 to redirect it towards secretion. EMBO J 22:5551–5560. doi:10.1093/emboj/cdg516

    Article  CAS  PubMed  Google Scholar 

  20. Wang H, Bloom O, Zhang M et al (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science 285:248–251. doi:10.1126/science.285.5425.248

    Article  CAS  PubMed  Google Scholar 

  21. Bell CW, Jiang W, Reich CF et al (2006) The extracellular release of HMGB1 during apoptotic cell death. Am J Physiol Cell Physiol 291:C1318–C1325. doi:10.1152/ajpcell.00616.2005

    Article  CAS  PubMed  Google Scholar 

  22. Jiang W, Bell CW, Pisetsky DS (2007) The relationship between apoptosis and HMGB1 release from murine macrophages stimulated with LPS or poly (I:C). J Immunol 178:6495–6503

    CAS  PubMed  Google Scholar 

  23. Stern D, Yan SD, Yan SF et al (2002) Receptor for advanced glycation endproducts: a multiligand receptor magnifying cell stress in diverse pathologic settings. Adv Drug Deliv Rev 54:1615–1625. doi:10.1016/S0169-409X(02)00160-6

    Article  CAS  PubMed  Google Scholar 

  24. Yang H, Wang H, Tracey KJ (2001) HMG-1 rediscovered as a cytokine. Shock 15:247–253. doi:10.1097/00024382-200115040-00001

    Article  CAS  PubMed  Google Scholar 

  25. Wang H, Yang H, Czura CJ et al (2001) HMGB1 as a late mediator of lethal systemic inflammation. Am J Respir Crit Care Med 164:1768–1773

    CAS  PubMed  Google Scholar 

  26. Yang H, Wang H, Czura CJ et al (2002) HMGB1 as a cytokine and therapeutic target. J Endotoxin Res 8:469–472. doi:10.1179/096805102125001091

    Article  CAS  PubMed  Google Scholar 

  27. Pisetsky DS, Erlandsson-Harris H, Andersson U (2008) High-mobility group box protein 1 (HMGB1): an alarmin mediating the pathogenesis of rheumatic disease. Arthritis Res Ther 10:209. doi:10.1186/ar2440

    Article  PubMed  Google Scholar 

  28. Curtin JF, Liu N, Candolfi M et al (2009) HMGB1 mediates endogenous TLR2 activation and brain tumor regression. PLoS Med 6:e10. doi:10.1371/journal.pmed.1000010

    Article  PubMed  Google Scholar 

  29. Harris HE, Raucci A (2006) Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep 7:774–778

    CAS  PubMed  Google Scholar 

  30. Kokkola R, Li J, Sundberg E et al (2003) Successful treatment of collagen-induced arthritis in mice and rats by targeting extracellular high mobility group box chromosomal protein 1 activity. Arthritis Rheum 48:2052–2058. doi:10.1002/art.11161

    Article  CAS  PubMed  Google Scholar 

  31. Taniguchi N, Kawahara K, Yone K et al (2003) High mobility group box chromosomal protein 1 plays a role in the pathogenesis of rheumatoid arthritis as a novel cytokine. Arthritis Rheum 48:971–981. doi:10.1002/art.10859

    Article  CAS  PubMed  Google Scholar 

  32. Urbonaviciute V, Furnrohr BG, Weber C et al (2007) Factors masking HMGB1 in human serum and plasma. J Leukoc Biol 81:67–74. doi:10.1189/jlb.0306196

    Article  CAS  PubMed  Google Scholar 

  33. Urbonaviciute V, Fürnrohr BG, Meister S et al (2008) Induction of inflammatory and immune responses by HMGB1-nucleosome complexes: implications for the pathogenesis of SLE. J Exp Med. doi:10.1084/jem.20081165

    PubMed  Google Scholar 

  34. Scaffidi P, Misteli T, Bianchi ME (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature 418:191–195. doi:10.1038/nature00858

    Article  CAS  PubMed  Google Scholar 

  35. Ayer LM, Senecal JL, Martin L et al (1994) Antibodies to high mobility group proteins in systemic sclerosis. J Rheumatol 21:2071–2075

    CAS  PubMed  Google Scholar 

  36. Rosenberg AM, Cordeiro DM (2000) Relationship between sex and antibodies to high mobility group proteins 1 and 2 in juvenile idiopathic arthritis. J Rheumatol 27:2489–2493

    CAS  PubMed  Google Scholar 

  37. Sobajima J, Ozaki S, Uesugi H et al (1998) Prevalence and characterization of perinuclear anti-neutrophil cytoplasmic antibodies (P-ANCA) directed against HMG1 and HMG2 in ulcerative colitis (UC). Clin Exp Immunol 111:402–407. doi:10.1046/j.1365-2249.1998.00491.x

    Article  CAS  PubMed  Google Scholar 

  38. Santoro P, De Andrea M, Migliaretti G et al (2002) High prevalence of autoantibodies against the nuclear high mobility group (HMG) protein SSRP1 in sera from patients with systemic lupus erythematosus, but not other rheumatic diseases. J Rheumatol 29:90–93

    CAS  PubMed  Google Scholar 

  39. Fineschi S, Borghi MO, Riboldi P et al (2004) Prevalence of autoantibodies against structure specific recognition protein 1 in systemic lupus erythematosus. Lupus 13:463–468. doi:10.1191/0961203304lu1049oa

    Article  CAS  PubMed  Google Scholar 

  40. Uesugi H, Ozaki S, Sobajima J et al (1998) Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases. J Rheumatol 25:703–709

    CAS  PubMed  Google Scholar 

  41. Tian J, Avalos AM, Mao SY et al (2007) Toll-like receptor 9-dependent activation by DNA-containing immune complexes is mediated by HMGB1 and RAGE. Nat Immunol 8:487–496. doi:10.1038/ni1457

    Article  CAS  PubMed  Google Scholar 

  42. Yang H, Ochani M, Li J et al (2004) Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc Natl Acad Sci USA 101:296–301. doi:10.1073/pnas.2434651100

    Article  CAS  PubMed  Google Scholar 

  43. Ulloa L, Ochani M, Yang H et al (2002) Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc Natl Acad Sci USA 99:12351–12356. doi:10.1073/pnas.192222999

    Article  CAS  PubMed  Google Scholar 

  44. Mao SY, Xu Y, Zhang J et al (2007) Antagonizing HMGB1 inhibits proteinuria in a murine model of lupus-like disease. J Immunol 178:131.24

    Google Scholar 

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Acknowledgments

This work was partly supported by grants from the National Natural Science Foundation of China (30571608, 30771848) and the key program of the National Natural Science Foundation of China (30830089).

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Authors and Affiliations

  1. Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, 81 Meishan Road, 230032, Hefei, Anhui, People’s Republic of China

    Hai-Feng Pan & Dong-Qing Ye

  2. Department of Pharmacology, Anhui Medical University, 81 Meishan Road, 230032, Hefei, Anhui, People’s Republic of China

    Guo-Cui Wu & Wei-Ping Li

  3. Department of Rheumatology, Anhui Provincial Hospital, 17 Lujiang Road, 230001, Hefei, Anhui, People’s Republic of China

    Xiang-Pei Li

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  1. Hai-Feng Pan
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  2. Guo-Cui Wu
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Correspondence to Dong-Qing Ye.

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Hai-Feng Pan and Guo-Cui Wu contributed equally to this work and should be considered co-first authors.

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Pan, HF., Wu, GC., Li, WP. et al. High Mobility Group Box 1: a potential therapeutic target for systemic lupus erythematosus. Mol Biol Rep 37, 1191–1195 (2010). https://doi.org/10.1007/s11033-009-9485-7

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