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Molecular Medicine

, Volume 18, Issue 11, pp 1437–1448 | Cite as

Chlorogenic Acid Attenuates High Mobility Group Box 1 (HMGB1) and Enhances Host Defense Mechanisms in Murine Sepsis

  • Chan-Ho Lee
  • Seong-Jin Yoon
  • Sun-Mee Lee
Research Article

Abstract

Sepsis is a complex, multifactorial, rapidly progressive disease characterized by an overwhelming activation of the immune system and the countervailing antiinflammatory response. In the current study in murine peritoneal macrophages, chlorogenic acid suppressed endotoxin-induced high mobility group box 1 (HMGB1) release in a concentration-dependent manner. Administration of chlorogenic acid also attenuated systemic HMGB1 accumulation in vivoand prevented mortality induced by endotoxemia and polymicrobial sepsis. The mechanisms of action of chlorogenic acid included attenuation of the increase in toll-like receptor (TLR)-4 expression and suppression of sepsis-induced signaling pathways, such as c-Jun NH2-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-κB, which are critical for cytokine release. The protection conferred by chlorogenic acid was achieved through modulation of cytokine and chemokine release, suppression of immune cell apoptosis and augmentation of bacterial elimination. Chlorogenic acid warrants further evaluation as a potential therapeutic agent for the treatment of sepsis and other potentially fatal systemic inflammatory disorders.

References

  1. 1.
    Hotchkiss RS, Karl IE. (2003) The pathophysiology and treatment of sepsis. N. Engl. J. Med. 348:138–50.CrossRefGoogle Scholar
  2. 2.
    Wang H, et al. (1999) HMG-1 as a late mediator of endotoxin lethality in mice. Science. 285:248–51.CrossRefGoogle Scholar
  3. 3.
    Riedemann NC, Guo RF, Ward PA. (2003) The enigma of sepsis. J. Clin. Invest. 112:460–7.CrossRefGoogle Scholar
  4. 4.
    Niggeweg R, Michael AJ, Martin C. (2004) Engineering plants with increased levels of the antioxidant chlorogenic acid. Nat. Biotechnol. 22:746–54.CrossRefGoogle Scholar
  5. 5.
    Stoclet JC, et al. (2004) Vascular protection by dietary polyphenols. Eur. J. Pharmacol. 500:299–313.CrossRefGoogle Scholar
  6. 6.
    Olmos A, et al. (2007) Effects of plant alkylphenols on cytokine production, tyrosine nitration and inflammatory damage in the efferent phase of contact hypersensitivity. Br. J. Pharmacol. 152:366–73.CrossRefGoogle Scholar
  7. 7.
    Zhang X, et al. (2010) Chlorogenic acid protects mice against lipopolysaccharide-induced acute lung injury. Injury. 41:746–52.CrossRefGoogle Scholar
  8. 8.
    Xu Y, et al. (2010) Protective effects of chlorogenic acid on acute hepatotoxicity induced by lipopolysaccharide in mice. Inflamm. Res. 59:871–7.CrossRefGoogle Scholar
  9. 9.
    Feng R, et al. (2005) Inhibition of activator protein-1, NF-kappaB, and MAPKs and induction of phase 2 detoxifying enzyme activity by chlorogenic acid. J. Biol. Chem. 280:27888–95.CrossRefGoogle Scholar
  10. 10.
    Cho ES, et al. (2009) Attenuation of oxidative neuronal cell death by coffee phenolic phytochemicals. Mutat. Res. 661:18–24.CrossRefGoogle Scholar
  11. 11.
    Institute of Laboratory Animal Resources; Commission on Life Sciences; National Research Council. (1996) Guide for the Care and Use of Laboratory Animals. Washington (DC): National Academy Press. [cited 2012 Mar 15]. Available from: https://doi.org/www.nap.edu/openbook.php?record_id=5140
  12. 12.
    Rittirsch D, Huber-Lang MS, Flierl MA, Ward PA. (2009) Immunodesign of experimental sepsis by cecal ligation and puncture. Nat. Protoc. 4:31–6.CrossRefGoogle Scholar
  13. 13.
    Ulloa L, et al. (2002) Ethyl pyruvate prevents lethality in mice with established lethal sepsis and systemic inflammation. Proc. Natl. Acad. Sci. U. S. A. 99:12351–6.CrossRefGoogle Scholar
  14. 14.
    Chomczynski P, Sacchi N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162:156–9.CrossRefGoogle Scholar
  15. 15.
    Freire-Garabal M, et al. (2002) Effects of fluoxetine on the activity of phagocytosis in stressed mice. Life Sci. 72:173–83.CrossRefGoogle Scholar
  16. 16.
    Ding AH, Nathan CF, Stuehr DJ. (1988) Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages: comparison of activating cytokines and evidence for independent production. J. Immunol. 141:2407–12.PubMedGoogle Scholar
  17. 17.
    Buras JA, Holzmann B, Sitkovsky M. (2005) Animal models of sepsis: setting the stage. Nat. Rev. Drug Discov. 4:854–65.CrossRefGoogle Scholar
  18. 18.
    Yang H, et al. (2004) Reversing established sepsis with antagonists of endogenous high-mobility group box 1. Proc. Natl. Acad. Sci. U. S. A. 101:296–301.CrossRefGoogle Scholar
  19. 19.
    Park JS, et al. (2004) Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J. Biol. Chem. 279:7370–7.CrossRefGoogle Scholar
  20. 20.
    Williams DL, et al. (2003) Modulation of tissue Toll-like receptor 2 and 4 during the early phases of polymicrobial sepsis correlates with mortality. Crit. Care Med. 31:1808–18.CrossRefGoogle Scholar
  21. 21.
    Rittirsch D, Flierl MA, Ward PA. (2008) Harmful molecular mechanisms in sepsis. Nat. Rev. Immunol. 8:776–87.CrossRefGoogle Scholar
  22. 22.
    Ebersole JL, Cappelli D. (2000) Acute-phase reactants in infections and inflammatory diseases. Periodontol. 2000 23:19–49.CrossRefGoogle Scholar
  23. 23.
    Heremans H, Dillen C, Put W, Van Damme J, Billiau A. (1992) Protective effect of anti-interleukin (IL)-6 antibody against endotoxin, associated with paradoxically increased IL-6 levels. Eur. J. Immunol. 22:2395–401.CrossRefGoogle Scholar
  24. 24.
    Kishimoto T. (1989) The biology of interleukin-6. Blood. 74:1–10.PubMedGoogle Scholar
  25. 25.
    Czura CJ, Tracey KJ. (2003) Targeting high mobility group box 1 as a late-acting mediator of inflammation. Crit. Care Med. 31:S46–50.CrossRefGoogle Scholar
  26. 26.
    Li W, et al. (2007) A cardiovascular drug rescues mice from lethal sepsis by selectively attenuating a late-acting proinflammatory mediator, high mobility group box 1. J. Immunol. 178:3856–64.CrossRefGoogle Scholar
  27. 27.
    Scaffidi P, Misteli T, Bianchi ME. (2002) Release of chromatin protein HMGB1 by necrotic cells triggers inflammation. Nature. 418:191–5.CrossRefGoogle Scholar
  28. 28.
    Salvemini D, Cuzzocrea S. (2003) Therapeutic potential of superoxide dismutase mimetics as therapeutic agents in critical care medicine. Crit. Care Med. 31:S29–38.CrossRefGoogle Scholar
  29. 29.
    Sessler CN, et al. (1995) Circulating ICAM-1 is increased in septic shock. Am. J. Respir. Crit. Care Med. 151:1420–7.CrossRefGoogle Scholar
  30. 30.
    Muller Kobold AC, et al. (2000) Leukocyte activation in sepsis; correlations with disease state and mortality. Intensive Care Med. 26:883–92.CrossRefGoogle Scholar
  31. 31.
    Yu M, et al. (2006) HMGB1 signals through tolllike receptor (TLR) 4 and TLR2. Shock. 26:174–9.CrossRefGoogle Scholar
  32. 32.
    Karin M, Ben-Neriah Y. (2000) Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu. Rev. Immunol. 18:621–63.CrossRefGoogle Scholar
  33. 33.
    Kopp EB, Medzhitov R. (1999) The Toll-receptor family and control of innate immunity. Curr. Opin. Immunol. 11:13–8.CrossRefGoogle Scholar
  34. 34.
    Akira S, Takeda K. (2004) Toll-like receptor signalling. Nat. Rev. Immunol. 4:499–511.CrossRefGoogle Scholar
  35. 35.
    van Zoelen MA, et al. (2009) Role of toll-like receptors 2 and 4, and the receptor for advanced glycation end products in high-mobility group box 1-induced inflammation in vivo. Shock. 31:280–4.CrossRefGoogle Scholar
  36. 36.
    Yang H, et al. (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. 107:11942–7.CrossRefGoogle Scholar
  37. 37.
    McCloskey CA, Kameneva MV, Uryash A, Gallo DJ, Billiar TR. (2004) Tissue hypoxia activates JNK in the liver during hemorrhagic shock. Shock 22:380–6.CrossRefGoogle Scholar
  38. 38.
    Abbas AK, Murphy KM, Sher A. (1996) Functional diversity of helper T lymphocytes. Nature. 383:787–93.CrossRefGoogle Scholar
  39. 39.
    Weighardt H, et al. (2002) Impaired monocyte IL-12 production before surgery as a predictive factor for the lethal outcome of postoperative sepsis. Ann. Surg. 235:560–7.CrossRefGoogle Scholar
  40. 40.
    Heidecke CD, et al. (1999) Selective defects of T lymphocyte function in patients with lethal intraabdominal infection. Am. J. Surg. 178:288–92.CrossRefGoogle Scholar
  41. 41.
    Fiuza C, et al. (2003) Inflammation-promoting activity of HMGB1 on human microvascular endothelial cells. Blood. 101:2652–60.CrossRefGoogle Scholar
  42. 42.
    Yan SF, et al. (2000) Egr-1, a master switch coordinating upregulation of divergent gene families underlying ischemic stress. Nat. Med. 6:1355–61.CrossRefGoogle Scholar
  43. 43.
    Ping D, et al. (2000) Sp1 binding is critical for promoter assembly and activation of the MCP-1 gene by tumor necrosis factor. J. Biol. Chem. 275:1708–14.CrossRefGoogle Scholar
  44. 44.
    Yoshimura T, Leonard EJ. (1991) Human monocyte chemoattractant protein-1 (MCP-1). Adv. Exp. Med. Biol. 305:47–56.CrossRefGoogle Scholar
  45. 45.
    Standiford TJ, Kunkel SL, Greenberger MJ, Laichalk LL, Strieter RM. (1996) Expression and regulation of chemokines in bacterial pneumonia. J. Leukoc. Biol. 59:24–8.CrossRefGoogle Scholar
  46. 46.
    Huber-Lang MS, et al. (2002) Complement-induced impairment of innate immunity during sepsis. J. Immunol. 169:3223–31.CrossRefGoogle Scholar
  47. 47.
    Czermak BJ, et al. (1999) Protective effects of C5a blockade in sepsis. Nat. Med. 5:788–92.CrossRefGoogle Scholar
  48. 48.
    Ward PA. (2008) Sepsis, apoptosis and complement. Biochem. Pharmacol. 76:1383–8.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.School of PharmacySungkyunkwan UniversitySuwonKorea

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