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Heat Shock Protein Responses in Septic Patients

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Regulation of Heat Shock Protein Responses

Part of the book series: Heat Shock Proteins ((HESP,volume 13))

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Abstract

Sepsis is a maladaptive inflammatory process in response to infectious agents, related to severe complications and poor outcomes. Despite advances, sepsis care remains a crucial challenge for intensive care units. The heat shock response during a septic process is primarily characterized by a dramatic upregulation of heat shock proteins (HSP), which are molecular chaperokines (intracellular chaperones and extracellular cytokines) exhibiting sophisticated protection mechanisms for living organisms. The main HSP representatives in sepsis are the heat shock proteins 70 and 90, which are ubiquitous chaperones with anti-apoptotic and immunomodulatory functions. The HSP family seems to create networks associated with a state of oxidative stress, capillary leak syndrome, immunoparalysis and with the hormonal changes occurring in sepsis.

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Abbreviations

ARDS:

Acute respiratory distress syndrome

ATP:

Adenosine-5-triphospate

eHSP:

Extracellular HSP

HDL:

High-density lipoprotein

hGRa:

Human glucocorticoid receptor a

HLA:

Human leukocyte antigen

HS:

Heat shock

HSC70:

Heat shock cognate protein 70

HSF1:

Heat shock factor 1

HSP:

Heat shock protein

ICU:

Intensive care unit

IFN:

Interferon-γ

iHSP:

Intracellular HSP

IL:

Interleukin

JDP:

J-domain protein

LDL:

Low-density lipoprotein

LPS:

Bacterial lipopolysacharide

MHC:

Major histocompatibility complex

mRNA:

Messenger ribonucleic acid; NF-κB, nuclear factor kappa-B

SIRS:

Systemic inflammatory response syndrome; SNPs, single nucleotide polymorphisms

TGF:

Tissue growth factor

TLR:

Toll like receptor

TNF-a:

Tumor necrosis factor alpha

References

  • Ambade, A., Catalano, D., Lim, A., & Mandrekar, P. (2012). Inhibition of hsp90 attenuates pro-inflammatory cytokines and prevents LPS induced liver injury. Hepatology, 55, 1585–1595.

    Article  CAS  Google Scholar 

  • Angus, D. C., Linde-Zwirble, W. T., Lidicker, J., Clermont, G., Carcillo, J., & Pinsky, M. R. (2001). Epidemiology of severe sepsis in the United States: Analysis of incidence, outcome, and associated costs of care. Critical Care Medicine, 29, 1303–1310.

    Article  CAS  Google Scholar 

  • Antonov, A., Snead, C., Gorshkov, B., Antonova, G. N., Verin, A. D., & Catravas, J. D. (2008). Heat shock protein 90 inhibitors protect and restore pulmonary endothelial barrier function. American Journal of Respiratory Cell and Molecular Biology, 39, 551–559.

    Article  CAS  Google Scholar 

  • Briassouli, E., Goukos, D., Daikos, G., Apostolou, K., Routsi, C., Nanas, S., & Briassoulis, G. (2014). Glutamine suppresses Hsp72 not Hsp90α and is not inducing Th1, Th2, or Th17 cytokine responses in human septic PBMCs. Nutrition, 30, 1185–1194.

    Article  CAS  Google Scholar 

  • Briassouli, E., Tzanoudaki, M., Goukos, D., Routsi, C., Nanas, S., Vardas, K., Apostolou, K., Kanariou, M., Daikos, G., & Briassoulis, G. (2015). Glutamine may repress the weak LPS and enhance the strong heat shock induction of monocyte and lymphocyte HSP72 proteins but may not modulate the HSP72 mRNA in patients with sepsis or trauma. BioMed Research International, 2015, 806042.

    Article  Google Scholar 

  • Briassoulis, G., Briassouli, E., Fitrolaki, D.-M., Plati, I., Apostolou, K., Tavladaki, T., & Spanaki, A.-M. (2014). Heat shock protein 72 expressing stress in sepsis: Unbridgeable gap between animal and human studies--a hypothetical “comparative” study. BioMed Research International, 2014, 101023.

    Article  Google Scholar 

  • Chan, J. Y. H., Ou, C.-C., Wang, L.-L., & Chan, S. H. H. (2004). Heat shock protein 70 confers cardiovascular protection during endotoxemia via inhibition of nuclear factor-kappaB activation and inducible nitric oxide synthase expression in the rostral ventrolateral medulla. Circulation, 110, 3560–3566.

    Article  CAS  Google Scholar 

  • Chatterjee, A., Dimitropoulou, C., Drakopanayiotakis, F., Antonova, G., Snead, C., Cannon, J., Venema, R. C., & Catravas, J. D. (2007). Heat shock protein 90 inhibitors prolong survival, attenuate inflammation, and reduce lung injury in murine sepsis. American Journal of Respiratory and Critical Care Medicine, 176, 667–675.

    Article  CAS  Google Scholar 

  • Chen, T., & Cao, X. (2010). Stress for maintaining memory: HSP70 as a mobile messenger for innate and adaptive immunity. European Journal of Immunology, 40, 1541–1544.

    Article  CAS  Google Scholar 

  • Davis, S. M., Clark, E. A. S., Nelson, L. T., & Silver, R. M. (2010). The association of innate immune response gene polymorphisms and puerperal group a streptococcal sepsis. American Journal of Obstetrics and Gynecology, 202, 308.e1–308.e8.

    Article  Google Scholar 

  • Fitrolaki, M.-D., Dimitriou, H., Venihaki, M., Katrinaki, M., Ilia, S., & Briassoulis, G. (2016). Increased extracellular heat shock protein 90α in severe sepsis and SIRS associated with multiple organ failure and related to acute inflammatory-metabolic stress response in children. Medicine (Baltimore), 95, e4651.

    Article  CAS  Google Scholar 

  • Frazier, W. J., & Hall, M. W. (2008). Immunoparalysis and adverse outcomes from critical illness. Pediatric Clinics of North America, 55, 647–668. xi.

    Article  Google Scholar 

  • Galic, S., Oakhill, J. S., & Steinberg, G. R. (2010). Adipose tissue as an endocrine organ. Molecular and Cellular Endocrinology, 316, 129–139.

    Article  CAS  Google Scholar 

  • Gelain, D. P., de Bittencourt Pasquali, M. A., M Comim, C., Grunwald, M. S., Ritter, C., Tomasi, C. D., Alves, S. C., Quevedo, J., Dal-Pizzol, F., & Moreira, J. C. F. (2011). Serum heat shock protein 70 levels, oxidant status, and mortality in sepsis. Shock, 35, 466–470.

    Article  CAS  Google Scholar 

  • Grunwald, M. S., Pires, A. S., Zanotto-Filho, A., Gasparotto, J., Gelain, D. P., Demartini, D. R., Schöler, C. M., de Bittencourt, P. I. H., & Moreira, J. C. F. (2014). The oxidation of HSP70 is associated with functional impairment and lack of stimulatory capacity. Cell Stress & Chaperones, 19, 913–925.

    Article  CAS  Google Scholar 

  • Gupta, A., Cooper, Z. A., Tulapurkar, M. E., Potla, R., Maity, T., Hasday, J. D., & Singh, I. S. (2013). Toll-like receptor agonists and febrile range hyperthermia synergize to induce heat shock protein 70 expression and extracellular release. The Journal of Biological Chemistry, 288, 2756–2766.

    Article  CAS  Google Scholar 

  • Hsu, H.-Y., Wu, H.-L., Tan, S.-K., Li, V. P.-H., Wang, W.-T., Hsu, J., & Cheng, C.-H. (2007). Geldanamycin interferes with the 90-kDa heat shock protein, affecting lipopolysaccharide-mediated interleukin-1 expression and apoptosis within macrophages. Molecular Pharmacology, 71, 344–356.

    Article  CAS  Google Scholar 

  • Hsu, J.-H., Yang, R.-C., Lin, S.-J., Liou, S.-F., Dai, Z.-K., Yeh, J.-L., & Wu, J.-R. (2014). Exogenous heat shock cognate protein 70 pretreatment attenuates cardiac and hepatic dysfunction with associated anti-inflammatory responses in experimental septic shock. Shock, 42, 540–547.

    Article  CAS  Google Scholar 

  • Jabandziev, P., Smerek, M., Michalek, J., Fedora, M., Kosinova, L., Hubacek, J. A., & Michalek, J. (2014). Multiple gene-to-gene interactions in children with sepsis: A combination of five gene variants predicts outcome of life-threatening sepsis. Critical Care, 18, R1.

    Article  Google Scholar 

  • Jayaprakash, P., Dong, H., Zou, M., Bhatia, A., O’Brien, K., Chen, M., Woodley, D. T., & Li, W. (2015). Hsp90α and Hsp90β together operate a hypoxia and nutrient paucity stress-response mechanism during wound healing. Journal of Cell Science, 128, 1475–1480.

    Article  CAS  Google Scholar 

  • Kang, Q., Chen, Y., Zhang, X., Yu, G., Wan, X., Wang, J., Bo, L., & Zhu, K. (2016). Heat shock protein A12B protects against sepsis-induced impairment in vascular endothelial permeability. The Journal of Surgical Research, 202, 87–94.

    Article  CAS  Google Scholar 

  • Lee, E. C.-H., Muñoz, C. X., McDermott, B. P., Beasley, K. N., Yamamoto, L. M., Hom, L. L., Casa, D. J., Armstrong, L. E., Kraemer, W. J., Anderson, J. M., et al. (2017). Extracellular and cellular Hsp72 differ as biomarkers in acute exercise/environmental stress and recovery. Scandinavian Journal of Medicine & Science in Sports, 27, 66–74.

    Article  Google Scholar 

  • Li, W., Sahu, D., & Tsen, F. (2012). Secreted heat shock protein-90 (Hsp90) in wound healing and cancer. Biochimica et Biophysica Acta, 1823, 730–741.

    Article  CAS  Google Scholar 

  • Li, X., Luo, R., Jiang, R., Meng, X., Wu, X., Zhang, S., & Hua, W. (2013). The role of the Hsp90/Akt pathway in myocardial calpain-induced caspase-3 activation and apoptosis during sepsis. BMC Cardiovascular Disorders, 13, 8.

    Article  Google Scholar 

  • Marino, L. V., Pathan, N., Meyer, R. W., Wright, V. J., & Habibi, P. (2016). An in vitro model to consider the effect of 2 mM glutamine and KNK437 on endotoxin-stimulated release of heat shock protein 70 and inflammatory mediators. Nutrition, 32, 375–383.

    Article  CAS  Google Scholar 

  • Mayer, M. P., & Bukau, B. (2005). Hsp70 chaperones: Cellular functions and molecular mechanism. Cellular and Molecular Life Sciences, 62, 670–684.

    Article  CAS  Google Scholar 

  • McConnell, K. W., Fox, A. C., Clark, A. T., Chang, N.-Y. N., Dominguez, J. A., Farris, A. B., Buchman, T. G., Hunt, C. R., & Coopersmith, C. M. (2011). The role of heat shock protein 70 in mediating age-dependent mortality in sepsis. Journal of Immunology, 186, 3718–3725.

    Article  CAS  Google Scholar 

  • Papadopoulos, P., Pistiki, A., Theodorakopoulou, M., Christodoulopoulou, T., Damoraki, G., Goukos, D., Briassouli, E., Dimopoulou, I., Armaganidis, A., Nanas, S., et al. (2017). Immunoparalysis: Clinical and immunological associations in SIRS and severe sepsis patients. Cytokine, 92, 83–92.

    Article  CAS  Google Scholar 

  • Pasqua, T., Filice, E., Mazza, R., Quintieri, A. M., Carmela Cerra, M., Iannacone, R., Melfi, D., Indiveri, C., Gattuso, A., & Angelone, T. (2015). Cardiac and hepatic role of r-AtHSP70: Basal effects and protection against ischemic and sepsis conditions. Journal of Cellular and Molecular Medicine, 19, 1492–1503.

    Article  CAS  Google Scholar 

  • Pociot, F., Rønningen, K. S., & Nerup, J. (1993). Polymorphic analysis of the human MHC-linked heat shock protein 70 (HSP70-2) and HSP70-Hom genes in insulin-dependent diabetes mellitus (IDDM). Scandinavian Journal of Immunology, 38, 491–495.

    Article  CAS  Google Scholar 

  • Radons, J. (2016). The human HSP70 family of chaperones: Where do we stand? Cell Stress & Chaperones, 21, 379–404.

    Article  CAS  Google Scholar 

  • Rohde, M., Daugaard, M., Jensen, M. H., Helin, K., Nylandsted, J., & Jäättelä, M. (2005). Members of the heat-shock protein 70 family promote cancer cell growth by distinct mechanisms. Genes & Development, 19, 570–582.

    Article  CAS  Google Scholar 

  • Shen, H.-H., Huang, S.-Y., Cheng, P.-Y., Chu, Y.-J., Chen, S.-Y., Lam, K.-K., & Lee, Y.-M. (2017). Involvement of HSP70 and HO-1 in the protective effects of raloxifene on multiple organ dysfunction syndrome by endotoxemia in ovariectomized rats. Menopause, 24, 959–969.

    Article  Google Scholar 

  • Singleton, K. D., & Wischmeyer, P. E. (2007). Glutamine’s protection against sepsis and lung injury is dependent on heat shock protein 70 expression. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 292, R1839–R1845.

    Article  CAS  Google Scholar 

  • Tavladaki, T., Spanaki, A. M., Dimitriou, H., Kondili, E., Choulaki, C., Georgopoulos, D., & Briassoulis, G. (2017). Similar metabolic, innate immunity, and Adipokine profiles in adult and pediatric sepsis versus systemic inflammatory response syndrome-a pilot study. Pediatric Critical Care Medicine, 18(11), e494–e505.

    Article  Google Scholar 

  • Tulapurkar, M. E., Ramarathnam, A., Hasday, J. D., & Singh, I. S. (2015). Bacterial lipopolysaccharide augments febrile-range hyperthermia-induced heat shock protein 70 expression and extracellular release in human THP1 cells. PLoS One, 10, e0118010.

    Article  Google Scholar 

  • Temple, S. E. L., Cheong, K. Y., Ardlie, K. G., Sayer, D., & Waterer, G. W. (2004). The septic shock associated HSPA1B1267 polymorphism influences production of HSPA1A and HSPA1B. Intensive Care Medicine, 30, 1761–1767.

    Google Scholar 

  • Vardas, K., Apostolou, K., Briassouli, E., Goukos, D., Psarra, K., Botoula, E., Tsagarakis, S., Magira, E., Routsi, C., Nanas, S., et al. (2014). Early response roles for prolactin cortisol and circulating and cellular levels of heat shock proteins 72 and 90α in severe sepsis and SIRS. BioMed Research International, 2014, 803561.

    Article  CAS  Google Scholar 

  • Vardas, K., Ilia, S., Sertedaki, A., Charmandari, E., Briassouli, E., Goukos, D., Apostolou, K., Psarra, K., Botoula, E., Tsagarakis, S., et al. (2017). Increased glucocorticoid receptor expression in sepsis is related to heat shock proteins, cytokines, and cortisol and is associated with increased mortality. Intensive Care Medicine Experimental, 5(10), 10.

    Article  Google Scholar 

  • Wang, Y.-L., Shen, H.-H., Cheng, P.-Y., Chu, Y.-J., Hwang, H.-R., Lam, K.-K., & Lee, Y.-M. (2016). 17-DMAG, an HSP90 inhibitor, ameliorates multiple organ dysfunction syndrome via induction of HSP70 in Endotoxemic rats. PLoS One, 11, e0155583.

    Article  Google Scholar 

  • Waterer, G. W., ElBahlawan, L., Quasney, M. W., Zhang, Q., Kessler, L. A., & Wunderink, R. G. (2003). Heat shock protein 70-2+1267 AA homozygotes have an increased risk of septic shock in adults with community-acquired pneumonia. Critical Care Medicine, 31, 1367–1372.

    Article  CAS  Google Scholar 

  • Wheeler, D. S., & Wong, H. R. (2007). Heat shock response and acute lung injury. Free Radical Biology & Medicine, 42, 1–14.

    Article  CAS  Google Scholar 

  • Zhao, Y., Tao, L., Jiang, D., Chen, X., Li, P., Ning, Y., Xiong, R., Liu, P., Peng, Y., & Zhou, Y.-G. (2013a). The -144C/a polymorphism in the promoter of HSP90beta is associated with multiple organ dysfunction scores. PLoS One, 8, e58646.

    Article  CAS  Google Scholar 

  • Zhao, Y., Huang, Z.-J., Rahman, M., Luo, Q., & Thorlacius, H. (2013b). Radicicol, an Hsp90 inhibitor, inhibits intestinal inflammation and leakage in abdominal sepsis. The Journal of Surgical Research, 182, 312–318.

    Article  CAS  Google Scholar 

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Acknowledgements

Authors’ original research, on which this review is based upon, has been co-financed by the European Union (European Social Fund (ESF)) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework (NSRF)-Research Funding Program: THALES.

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Authors and Affiliations

  1. Pediatric Intensive Care Unit, University Hospital, University of Crete, Heraklion, Greece

    Marianna Miliaraki, Stavroula Ilia & George Briassoulis

  2. First Department of Pediatrics, Athens University, Athens, Greece

    Efrossini Briassouli

Authors
  1. Marianna Miliaraki
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  2. Efrossini Briassouli
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  3. Stavroula Ilia
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  4. George Briassoulis
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Corresponding author

Correspondence to George Briassoulis .

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Editors and Affiliations

  1. Department of Medicine and Precision Therapeutics Proteogenomics Diagnostic Center, Eleanor N. Dana Cancer Center, University of Toledo College of Medicine and Life Sciences, Toledo, Ohio, USA

    Alexzander A A Asea

  2. Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Punit Kaur

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Miliaraki, M., Briassouli, E., Ilia, S., Briassoulis, G. (2018). Heat Shock Protein Responses in Septic Patients. In: Asea, A., Kaur, P. (eds) Regulation of Heat Shock Protein Responses. Heat Shock Proteins, vol 13. Springer, Cham. https://doi.org/10.1007/978-3-319-74715-6_15

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