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Chaperones in Sterile Inflammation and Injury

  • Asmita Choudhury
  • Pranoti MandrekarEmail author
Chapter
Part of the Heat Shock Proteins book series (HESP, volume 16)

Abstract

Heat shock proteins (Hsp) are highly conserved proteins and their expression increases in response to stress stimuli for the maintenance of cellular homeostasis. Cellular stress conditions like hypoxia, change in pH, and metabolic changes are typically associated with upregulation of HSP. In addition to their traditional role of protein refolding or degradation during maintenance of homeostasis, Hsp also acts as key modulators of innate and adaptive immune pathways and play an important role in inflammation and host defense mechanisms. Several pathological conditions such as chronic inflammatory diseases and cancer are typically marked with an elevated expression of HSP. Increasing evidence demonstrates that Hsp can be secreted in the extracellular milieu during disease conditions. These proteins are released into the extracellular spaces either by necrotic cell death or by active secretion via exosomes. Exosomes containing Hsp can communicate and release exosomal contents to elicit immune cell activation. Thus, increased levels of Hsp can be considered as a danger signal both intracellularly, for its ability to chaperone inflammatory signaling molecules as well as extracellularly, for eliciting the activation of immune cells via exosomal communications. This chapter summarizes the chaperone role of HSP in serving as regulators of the immune response in chronic disease conditions.

Keywords

Chaperones DAMPs Exosome Heat shock factor 1 Heat shock proteins Inflammation 

Abbreviations

17-AAG

17-allylamino-17-dimethoxy-geldanamycin

17-DMAG

17-Dimethylaminoethylamino-17-dimethoxygeldenamycin

AP-1

Activator protein-1

APC

Antigen presenting cells

CDC37

Cell division cycle-37

CpG ODN

CpG-containing oligodeoxynuceotide

CTL

Cytotoxic T lymphocyte

CXCL10

C-X-C motif ligand-10

DAMP

Damage associated molecular pattern

DC

Dendritic cell

DMA

5,5-(N-N-Dimethyl)-amiloride hydrochloride

ERK

Extracellular signal-regulated kinases

HDGF

Hepatoma derived growth factor

HCV

Hepatitis C virus

HMGB1

High mobility group box 1

HSE

Heat shock element

HSF1

Heat shock factor 1

HSP

Heat shock protein

HSR

Heat shock response

I/R

Ischemia/reperfusion

IFN

Interferon

IKK

IκB kinase

IL

Interleukin

IRAK

IL-1 receptor-associated kinase

IRF3

IFN regulatory factor 3

JAK

Janus kinase

JNK

c-Jun amino-terminal kinases

LPS

Lipopolysaccharide

MAPK

Mitogen-activated protein kinases

MCP-1

Monocyte chemoattractant protein-1

MHC

Major histocompatibility complex

MKK

MAP kinase kinase

MMP-2

Matrix metalloproteinases-2

NEMO

NF-κB essential modulator

NF-κB

Nuclear factor-kappa B

NK

Natural killer

NLR

Nod-like receptor

PAMP

Pathogen associated molecular pattern

PBMC

Peripheral blood mononuclear cells

PRR

Pattern recognition receptor

RA

Rheumatoid arthritis

RAGE

Receptor for advanced glycation end products

RANTES

Regulated on activation, normal T cell expressed and secreted

RIP

Receptor interacting kinase

RLR

RIG-1-like receptor

RNS

Reactive nitrogen species

ROS

Reactive oxygen species

TAB

TAK-1 binding proteins

TAK1

TGF-β activated kinase 1

TANK

TRAF-associated NF-κB activator

TBK1

TANK-binding kinase 1

TGF-β

Tumor growth factor-beta

TIR

Toll/IL-1 receptor

TLR

Toll-like receptor

TNFR1

Tumor necrosis factor receptor1

TNFα

Tumor necrosis factor-alpha

TRAF6

Tumor necrosis factor receptor (TNF-R)-associated factor-6

TRAM

TRIF related adaptor molecule

TRIF

Toll/IL- receptor domain containing adaptor inducing IFN-β

Notes

Acknowledgements

This work was supported by grant # RO1 AA17986-01 and RO1 AA25289-01 (to PM) from the National Institute of Alcohol Abuse and Alcoholism, U.S. National Institutes of Health, Bethesda, MD, USA.

References

  1. Adhuna P, Mukhopadhyay B, Bhatnagar R (1997) Modulation of macrophage heat shock proteins (HSPs) expression in response to intracellular infection by virulent and avirulent strains of Leishmania donovani. Biochem Mol Biol Int 43:1265–1275PubMedGoogle Scholar
  2. Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4:499–511PubMedCrossRefGoogle Scholar
  3. Alford KA, Glennie S, Turrell BR, Rawlinson L, Saklatvala J, Dean JL (2007) Heat shock protein 27 functions in inflammatory gene expression and transforming growth factor-beta-activated kinase-1 (TAK1)-mediated signaling. J Biol Chem 282:6232–6241PubMedCrossRefGoogle Scholar
  4. Ambade A, Catalano D, Lim A, Mandrekar P (2012) Inhibition of heat shock protein (molecular weight 90 kDa) attenuates proinflammatory cytokines and prevents lipopolysaccharide-induced liver injury in mice. Hepatology 55:1585–1595PubMedPubMedCentralCrossRefGoogle Scholar
  5. Ambade A, Catalano D, Lim A, Kopoyan A, Shaffer SA, Mandrekar P (2014) Inhibition of heat shock protein 90 alleviates steatosis and macrophage activation in murine alcoholic liver injury. J Hepatol 61:903–911PubMedPubMedCentralCrossRefGoogle Scholar
  6. Ao L, Zhai Y, Jin C, Cleveland JC, Fullerton DA, Meng X (2016) Attenuated recovery of contractile function in aging hearts following global ischemia/reperfusion: role of extracellular HSP27 and TLR4. Mol Med 23:863PubMedGoogle Scholar
  7. Armijo G, Okerblom J, Cauvi DM, Lopez V, Schlamadinger DE, Kim J, Arispe N, De Maio A (2014) Interaction of heat shock protein 70 with membranes depends on the lipid environment. Cell Stress Chaperones 19:877–886PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bae J, Munshi A, Li C, Samur M, Prabhala R, Mitsiades C, Anderson KC, Munshi NC (2013) Heat shock protein 90 is critical for regulation of phenotype and functional activity of human T lymphocytes and NK cells. J Immunol 190:1360–1371PubMedCrossRefGoogle Scholar
  9. Banerjee S, Lin CF, Skinner KA, Schiffhauer LM, Peacock J, Hicks DG, Redmond EM, Morrow D, Huston A, Shayne M et al (2011) Heat shock protein 27 differentiates tolerogenic macrophages that may support human breast cancer progression. Cancer Res 71:318–327PubMedCrossRefGoogle Scholar
  10. Bar-Lavan Y, Kosolapov L, Frumkin A, Ben-Zvi A (2012) Regulation of cellular protein quality control networks in a multicellular organism. FEBS J 279:526–531PubMedCrossRefGoogle Scholar
  11. Basu S, Binder RJ, Suto R, Anderson KM, Srivastava PK (2000) Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway. Int Immunol 12:1539–1546PubMedCrossRefGoogle Scholar
  12. Basu S, Binder RJ, Ramalingam T, Srivastava PK (2001) CD91 is a common receptor for heat shock proteins gp96, hsp90, hsp70, and calreticulin. Immunity 14:303–313PubMedCrossRefGoogle Scholar
  13. Bausero MA, Gastpar R, Multhoff G, Asea A (2005) Alternative mechanism by which IFN-gamma enhances tumor recognition: active release of heat shock protein 72. J Immunol 175:2900–2912PubMedPubMedCentralCrossRefGoogle Scholar
  14. Becker B, Multhoff G, Farkas B, Wild PJ, Landthaler M, Stolz W, Vogt T (2004) Induction of Hsp90 protein expression in malignant melanomas and melanoma metastases. Exp Dermatol 13:27–32PubMedCrossRefGoogle Scholar
  15. Beninson LA, Brown PN, Loughridge AB, Saludes JP, Maslanik T, Hills AK, Woodworth T, Craig W, Yin H, Fleshner M (2014) Acute stressor exposure modifies plasma exosome-associated heat shock protein 72 (Hsp72) and microRNA (miR-142-5p and miR-203). PLoS One 9:e108748PubMedPubMedCentralCrossRefGoogle Scholar
  16. Berwin B, Reed RC, Nicchitta CV (2001) Virally induced lytic cell death elicits the release of immunogenic GRP94/gp96. J Biol Chem 276:21083–21088PubMedCrossRefGoogle Scholar
  17. Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81:1–5PubMedCrossRefGoogle Scholar
  18. Binder RJ (2014) Functions of heat shock proteins in pathways of the innate and adaptive immune system. J Immunol 193:5765–5771PubMedPubMedCentralCrossRefGoogle Scholar
  19. Binder RJ, Blachere NE, Srivastava PK (2001) Heat shock protein-chaperoned peptides but not free peptides introduced into the cytosol are presented efficiently by major histocompatibility complex I molecules. J Biol Chem 276:17163–17171PubMedCrossRefGoogle Scholar
  20. Blanchard N, Lankar D, Faure F, Regnault A, Dumont C, Raposo G, Hivroz C (2002) TCR activation of human T cells induces the production of exosomes bearing the TCR/CD3/zeta complex. J Immunol 168:3235–3241PubMedCrossRefGoogle Scholar
  21. Boog CJ, de Graeff-Meeder ER, Lucassen MA, van der Zee R, Voorhorst-Ogink MM, van Kooten PJ, Geuze HJ, van Eden W (1992) Two monoclonal antibodies generated against human hsp60 show reactivity with synovial membranes of patients with juvenile chronic arthritis. J Exp Med 175:1805–1810PubMedCrossRefGoogle Scholar
  22. Brenner C, Galluzzi L, Kepp O, Kroemer G (2013) Decoding cell death signals in liver inflammation. J Hepatol 59:583–594PubMedCrossRefGoogle Scholar
  23. Broquet AH, Thomas G, Masliah J, Trugnan G, Bachelet M (2003) Expression of the molecular chaperone Hsp70 in detergent-resistant microdomains correlates with its membrane delivery and release. J Biol Chem 278:21601–21606PubMedCrossRefGoogle Scholar
  24. Callahan MK, Garg M, Srivastava PK (2008) Heat-shock protein 90 associates with N-terminal extended peptides and is required for direct and indirect antigen presentation. Proc Natl Acad Sci U S A 105:1662–1667PubMedPubMedCentralCrossRefGoogle Scholar
  25. Campisi J, Leem TH, Fleshner M (2003) Stress-induced extracellular Hsp72 is a functionally significant danger signal to the immune system. Cell Stress Chaperones 8:272–286PubMedPubMedCentralCrossRefGoogle Scholar
  26. Chalmin F, Ladoire S, Mignot G, Vincent J, Bruchard M, Remy-Martin JP, Boireau W, Rouleau A, Simon B, Lanneau D et al (2010) Membrane-associated Hsp72 from tumor-derived exosomes mediates STAT3-dependent immunosuppressive function of mouse and human myeloid-derived suppressor cells. J Clin Invest 120:457–471PubMedPubMedCentralGoogle Scholar
  27. Chen G, Cao P, Goeddel DV (2002) TNF-induced recruitment and activation of the IKK complex require Cdc37 and Hsp90. Mol Cell 9:401–410PubMedCrossRefGoogle Scholar
  28. Cheng CF, Fan J, Fedesco M, Guan S, Li Y, Bandyopadhyay B, Bright AM, Yerushalmi D, Liang M, Chen M et al (2008) Transforming growth factor alpha (TGFalpha)-stimulated secretion of HSP90alpha: using the receptor LRP-1/CD91 to promote human skin cell migration against a TGFbeta-rich environment during wound healing. Mol Cell Biol 28:3344–3358PubMedPubMedCentralCrossRefGoogle Scholar
  29. Cho JA, Lee YS, Kim SH, Ko JK, Kim CW (2009) MHC independent anti-tumor immune responses induced by Hsp70-enriched exosomes generate tumor regression in murine models. Cancer Lett 275:256–265PubMedCrossRefGoogle Scholar
  30. Choudhury A, Khole VV (2013) HSP90 antibodies: a detrimental factor responsible for ovarian dysfunction. Am J Reprod Immunol 70:372–385PubMedGoogle Scholar
  31. Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z (2005) Induction of heat shock proteins in B-cell exosomes. J Cell Sci 118:3631–3638PubMedCrossRefGoogle Scholar
  32. Dai S, Wan T, Wang B, Zhou X, Xiu F, Chen T, Wu Y, Cao X (2005) More efficient induction of HLA-A*0201-restricted and carcinoembryonic antigen (CEA)-specific CTL response by immunization with exosomes prepared from heat-stressed CEA-positive tumor cells. Clin Cancer Res 11:7554–7563PubMedCrossRefGoogle Scholar
  33. Daniels GA, Sanchez-Perez L, Diaz RM, Kottke T, Thompson J, Lai M, Gough M, Karim M, Bushell A, Chong H et al (2004) A simple method to cure established tumors by inflammatory killing of normal cells. Nat Biotechnol 22:1125–1132PubMedCrossRefGoogle Scholar
  34. De Maio A (2011) Extracellular heat shock proteins, cellular export vesicles, and the stress observation system: a form of communication during injury, infection, and cell damage. It is never known how far a controversial finding will go! Dedicated to Ferruccio Ritossa. Cell Stress Chaperones 16:235–249PubMedCrossRefPubMedCentralGoogle Scholar
  35. De Maio A, Vazquez D (2013) Extracellular heat shock proteins: a new location, a new function. Shock 40:239–246PubMedPubMedCentralCrossRefGoogle Scholar
  36. De Nardo D, Masendycz P, Ho S, Cross M, Fleetwood AJ, Reynolds EC, Hamilton JA, Scholz GM (2005) A central role for the Hsp90.Cdc37 molecular chaperone module in interleukin-1 receptor-associated-kinase-dependent signaling by toll-like receptors. J Biol Chem 280:9813–9822PubMedCrossRefGoogle Scholar
  37. Dokladny K, Lobb R, Wharton W, Ma TY, Moseley PL (2010) LPS-induced cytokine levels are repressed by elevated expression of HSP70 in rats: possible role of NF-kappaB. Cell Stress Chaperones 15:153–163PubMedCrossRefGoogle Scholar
  38. Dong C, Davis RJ, Flavell RA (2002) MAP kinases in the immune response. Annu Rev Immunol 20:55–72PubMedCrossRefGoogle Scholar
  39. Dybdahl B, Wahba A, Lien E, Flo TH, Waage A, Qureshi N, Sellevold OF, Espevik T, Sundan A (2002) Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through toll-like receptor-4. Circulation 105:685–690PubMedCrossRefGoogle Scholar
  40. Elsner L, Muppala V, Gehrmann M, Lozano J, Malzahn D, Bickeboller H, Brunner E, Zientkowska M, Herrmann T, Walter L et al (2007) The heat shock protein HSP70 promotes mouse NK cell activity against tumors that express inducible NKG2D ligands. J Immunol 179:5523–5533PubMedCrossRefGoogle Scholar
  41. Fajac I, Roisman GL, Lacronique J, Polla BS, Dusser DJ (1997) Bronchial gamma delta T-lymphocytes and expression of heat shock proteins in mild asthma. Eur Respir J 10:633–638PubMedGoogle Scholar
  42. Ferrarini M, Heltai S, Zocchi MR, Rugarli C (1992) Unusual expression and localization of heat-shock proteins in human tumor cells. Int J Cancer 51:613–619PubMedCrossRefGoogle Scholar
  43. Fleshner M, Crane CR (2017) Exosomes, DAMPs and miRNA: features of stress physiology and immune homeostasis. Trends Immunol 38:768–776PubMedPubMedCentralCrossRefGoogle Scholar
  44. Galkina E, Ley K (2009) Immune and inflammatory mechanisms of atherosclerosis (*). Annu Rev Immunol 27:165–197PubMedPubMedCentralCrossRefGoogle Scholar
  45. Ganter MT, Ware LB, Howard M, Roux J, Gartland B, Matthay MA, Fleshner M, Pittet JF (2006) Extracellular heat shock protein 72 is a marker of the stress protein response in acute lung injury. Am J Phys Lung Cell Mol Phys 291:L354–L361Google Scholar
  46. Gao P, Sun X, Chen X, Subjeck J, Wang XY (2009) Secretion of stress protein grp170 promotes immune-mediated inhibition of murine prostate tumor. Cancer Immunol Immunother 58:1319–1328PubMedPubMedCentralCrossRefGoogle Scholar
  47. Gaston JS, Life PF, Bailey LC, Bacon PA (1989) In vitro responses to a 65-kilodalton mycobacterial protein by synovial T cells from inflammatory arthritis patients. J Immunol 143:2494–2500PubMedGoogle Scholar
  48. Gastpar R, Gehrmann M, Bausero MA, Asea A, Gross C, Schroeder JA, Multhoff G (2005) Heat shock protein 70 surface-positive tumor exosomes stimulate migratory and cytolytic activity of natural killer cells. Cancer Res 65:5238–5247PubMedPubMedCentralCrossRefGoogle Scholar
  49. Gidalevitz T, Prahlad V, Morimoto RI (2011) The stress of protein misfolding: from single cells to multicellular organisms. Cold Spring Harb Perspect Biol 3:a009704PubMedPubMedCentralCrossRefGoogle Scholar
  50. Giuliano JS Jr, Lahni PM, Wong HR, Wheeler DS (2011) Pediatric sepsis – part V: extracellular heat shock proteins: alarmins for the host immune system. Open Inflamm J 4:49–60PubMedPubMedCentralCrossRefGoogle Scholar
  51. Goldstein MG, Li Z (2009) Heat-shock proteins in infection-mediated inflammation-induced tumorigenesis. J Hematol Oncol 2:5PubMedPubMedCentralCrossRefGoogle Scholar
  52. Gomez-Pastor R, Burchfiel ET, Thiele DJ (2017) Regulation of heat shock transcription factors and their roles in physiology and disease. Nat Rev Mol Cell Biol 19:4–19PubMedPubMedCentralCrossRefGoogle Scholar
  53. Graner MW, Cumming RI, Bigner DD (2007) The heat shock response and chaperones/heat shock proteins in brain tumors: surface expression, release, and possible immune consequences. J Neurosci 27:11214–11227PubMedCrossRefGoogle Scholar
  54. Graner MW, Alzate O, Dechkovskaia AM, Keene JD, Sampson JH, Mitchell DA, Bigner DD (2009) Proteomic and immunologic analyses of brain tumor exosomes. FASEB J 23:1541–1557PubMedPubMedCentralCrossRefGoogle Scholar
  55. Greening DW, Gopal SK, Xu R, Simpson RJ, Chen W (2015) Exosomes and their roles in immune regulation and cancer. Semin Cell Dev Biol 40:72–81PubMedCrossRefGoogle Scholar
  56. Gupta S, Knowlton AA (2007) HSP60 trafficking in adult cardiac myocytes: role of the exosomal pathway. Am J Physiol Heart Circ Physiol 292:H3052–H3056PubMedCrossRefGoogle Scholar
  57. Guzhova I, Kislyakova K, Moskaliova O, Fridlanskaya I, Tytell M, Cheetham M, Margulis B (2001) In vitro studies show that Hsp70 can be released by glia and that exogenous Hsp70 can enhance neuronal stress tolerance. Brain Res 914:66–73PubMedCrossRefGoogle Scholar
  58. Hance MW, Nolan KD, Isaacs JS (2014) The double-edged sword: conserved functions of extracellular hsp90 in wound healing and cancer. Cancers (Basel) 6:1065–1097CrossRefGoogle Scholar
  59. Hastie AT, Everts KB, Zangrilli J, Shaver JR, Pollice MB, Fish JE, Peters SP (1997) HSP27 elevated in mild allergic inflammation protects airway epithelium from H2SO4 effects. Am J Phys 273:L401–L409Google Scholar
  60. Hayden MS, West AP, Ghosh S (2006) NF-kappaB and the immune response. Oncogene 25:6758–6780PubMedCrossRefGoogle Scholar
  61. Hegmans JP, Bard MP, Hemmes A, Luider TM, Kleijmeer MJ, Prins JB, Zitvogel L, Burgers SA, Hoogsteden HC, Lambrecht BN (2004) Proteomic analysis of exosomes secreted by human mesothelioma cells. Am J Pathol 164:1807–1815PubMedPubMedCentralCrossRefGoogle Scholar
  62. Hightower LE, Guidon PT Jr (1989) Selective release from cultured mammalian cells of heat-shock (stress) proteins that resemble glia-axon transfer proteins. J Cell Physiol 138:257–266PubMedCrossRefGoogle Scholar
  63. Huang QQ, Sobkoviak R, Jockheck-Clark AR, Shi B, Mandelin AM 2nd, Tak PP, Haines GK 3rd, Nicchitta CV, Pope RM (2009) Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J Immunol 182:4965–4973PubMedPubMedCentralCrossRefGoogle Scholar
  64. Hunter-Lavin C, Davies EL, Bacelar MM, Marshall MJ, Andrew SM, Williams JH (2004) Hsp70 release from peripheral blood mononuclear cells. Biochem Biophys Res Commun 324:511–517PubMedCrossRefGoogle Scholar
  65. Hurwitz MD, Kaur P, Nagaraja GM, Bausero MA, Manola J, Asea A (2010) Radiation therapy induces circulating serum Hsp72 in patients with prostate cancer. Radiother Oncol 95:350–358PubMedPubMedCentralCrossRefGoogle Scholar
  66. Jee H (2016) Size dependent classification of heat shock proteins: a mini-review. J Exerc Rehabil 12:255–259PubMedPubMedCentralCrossRefGoogle Scholar
  67. Kline MP, Morimoto RI (1997) Repression of the heat shock factor 1 transcriptional activation domain is modulated by constitutive phosphorylation. Mol Cell Biol 17:2107–2115PubMedPubMedCentralCrossRefGoogle Scholar
  68. Kolinski T, Marek-Trzonkowska N, Trzonkowski P, Siebert J (2016) Heat shock proteins (HSPs) in the homeostasis of regulatory T cells (Tregs). Cent Eur J Immunol 41:317–323PubMedPubMedCentralCrossRefGoogle Scholar
  69. Kono H, Rock KL (2008) How dying cells alert the immune system to danger. Nat Rev Immunol 8:279–289PubMedPubMedCentralCrossRefGoogle Scholar
  70. Kunisawa J, Shastri N (2006) Hsp90alpha chaperones large C-terminally extended proteolytic intermediates in the MHC class I antigen processing pathway. Immunity 24:523–534PubMedCrossRefGoogle Scholar
  71. Lancaster GI, Febbraio MA (2005) Exosome-dependent trafficking of HSP70: a novel secretory pathway for cellular stress proteins. J Biol Chem 280:23349–23355PubMedCrossRefGoogle Scholar
  72. Land WG (2015) The role of damage-associated molecular patterns (DAMPs) in human diseases: part II: DAMPs as diagnostics, prognostics and therapeutics in clinical medicine. Sultan Qaboos Univ Med J 15:e157–e170PubMedPubMedCentralGoogle Scholar
  73. Lee JH, Lee YK, Lim JJ, Byun HO, Park I, Kim GH, Xu WG, Wang HJ, Yoon G (2015) Mitochondrial respiratory dysfunction induces claudin-1 expression via reactive oxygen species-mediated heat shock factor 1 activation, leading to hepatoma cell invasiveness. J Biol Chem 290:21421–21431PubMedPubMedCentralCrossRefGoogle Scholar
  74. Lewis J, Devin A, Miller A, Lin Y, Rodriguez Y, Neckers L, Liu ZG (2000) Disruption of hsp90 function results in degradation of the death domain kinase, receptor-interacting protein (RIP), and blockage of tumor necrosis factor-induced nuclear factor-kappaB activation. J Biol Chem 275:10519–10526PubMedCrossRefGoogle Scholar
  75. Li W, Sahu D, Tsen F (2012) Secreted heat shock protein-90 (Hsp90) in wound healing and cancer. Biochim Biophys Acta 1823:730–741PubMedCrossRefGoogle Scholar
  76. Li X, Wang S, Zhu R, Li H, Han Q, Zhao RC (2016) Lung tumor exosomes induce a pro-inflammatory phenotype in mesenchymal stem cells via NFkappaB-TLR signaling pathway. J Hematol Oncol 9:42PubMedPubMedCentralCrossRefGoogle Scholar
  77. Lindquist S, Craig EA (1988) The heat-shock proteins. Annu Rev Genet 22:631–677PubMedCrossRefGoogle Scholar
  78. Lis J, Wu C (1993) Protein traffic on the heat shock promoter: parking, stalling, and trucking along. Cell 74:1–4CrossRefGoogle Scholar
  79. Liu B, Yang Y, Qiu Z, Staron M, Hong F, Li Y, Wu S, Li Y, Hao B, Bona R et al (2010) Folding of toll-like receptors by the HSP90 paralogue gp96 requires a substrate-specific cochaperone. Nat Commun 1:79PubMedCrossRefGoogle Scholar
  80. Lv LH, Wan YL, Lin Y, Zhang W, Yang M, Li GL, Lin HM, Shang CZ, Chen YJ, Min J (2012) Anticancer drugs cause release of exosomes with heat shock proteins from human hepatocellular carcinoma cells that elicit effective natural killer cell antitumor responses in vitro. J Biol Chem 287:15874–15885PubMedPubMedCentralCrossRefGoogle Scholar
  81. Malik ZA, Kott KS, Poe AJ, Kuo T, Chen L, Ferrara KW, Knowlton AA (2013) Cardiac myocyte exosomes: stability, HSP60, and proteomics. Am J Physiol Heart Circ Physiol 304:H954–H965PubMedPubMedCentralCrossRefGoogle Scholar
  82. Mambula SS, Calderwood SK (2006) Heat shock protein 70 is secreted from tumor cells by a nonclassical pathway involving lysosomal endosomes. J Immunol 177:7849–7857PubMedCrossRefGoogle Scholar
  83. Mandrekar P, Catalano D, Jeliazkova V, Kodys K (2008) Alcohol exposure regulates heat shock transcription factor binding and heat shock proteins 70 and 90 in monocytes and macrophages: implication for TNF-alpha regulation. J Leukoc Biol 84:1335–1345PubMedPubMedCentralCrossRefGoogle Scholar
  84. Martin-Murphy BV, Holt MP, Ju C (2010) The role of damage associated molecular pattern molecules in acetaminophen-induced liver injury in mice. Toxicol Lett 192:387–394PubMedCrossRefGoogle Scholar
  85. Matzinger P (1994) Tolerance, danger, and the extended family. Annu Rev Immunol 12:991–1045PubMedCrossRefGoogle Scholar
  86. McCready J, Sims JD, Chan D, Jay DG (2010) Secretion of extracellular hsp90alpha via exosomes increases cancer cell motility: a role for plasminogen activation. BMC Cancer 10:294PubMedPubMedCentralCrossRefGoogle Scholar
  87. Medzhitov R, Janeway CA Jr (1997) Innate immunity: impact on the adaptive immune response. Curr Opin Immunol 9:4–9PubMedCrossRefGoogle Scholar
  88. Menay F, Herschlik L, De Toro J, Cocozza F, Tsacalian R, Gravisaco MJ, Di Sciullo MP, Vendrell A, Waldner CI, Mongini C (2017) Exosomes isolated from ascites of T-cell lymphoma-bearing mice expressing surface CD24 and HSP-90 induce a tumor-specific immune response. Front Immunol 8:286PubMedPubMedCentralCrossRefGoogle Scholar
  89. Merendino AM, Paul C, Vignola AM, Costa MA, Melis M, Chiappara G, Izzo V, Bousquet J, Arrigo AP (2002) Heat shock protein-27 protects human bronchial epithelial cells against oxidative stress-mediated apoptosis: possible implication in asthma. Cell Stress Chaperones 7:269–280PubMedPubMedCentralCrossRefGoogle Scholar
  90. Merendino AM, Bucchieri F, Campanella C, Marciano V, Ribbene A, David S, Zummo G, Burgio G, Corona DF, Conway de Macario E et al (2010) Hsp60 is actively secreted by human tumor cells. PLoS One e9247:5Google Scholar
  91. Meylan E, Burns K, Hofmann K, Blancheteau V, Martinon F, Kelliher M, Tschopp J (2004) RIP1 is an essential mediator of Toll-like receptor 3-induced NF-kappa B activation. Nat Immunol 5:503–507PubMedCrossRefGoogle Scholar
  92. Morimoto RI (1998) Regulation of the heat shock transcriptional response: cross talk between a family of heat shock factors, molecular chaperones, and negative regulators. Genes Dev 12:3788–3796PubMedCrossRefGoogle Scholar
  93. Multhoff G, Botzler C, Jennen L, Schmidt J, Ellwart J, Issels R (1997) Heat shock protein 72 on tumor cells: a recognition structure for natural killer cells. J Immunol 158:4341–4350PubMedPubMedCentralGoogle Scholar
  94. Muralidharan S, Mandrekar P (2013) Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. J Leukoc Biol 94:1167–1184PubMedPubMedCentralCrossRefGoogle Scholar
  95. Nathan C, Shiloh MU (2000) Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc Natl Acad Sci U S A 97:8841–8848PubMedPubMedCentralCrossRefGoogle Scholar
  96. Neckers L (2007) Heat shock protein 90: the cancer chaperone. J Biosci 32:517–530PubMedCrossRefGoogle Scholar
  97. Noessner E, Gastpar R, Milani V, Brandl A, Hutzler PJ, Kuppner MC, Roos M, Kremmer E, Asea A, Calderwood SK et al (2002) Tumor-derived heat shock protein 70 peptide complexes are cross-presented by human dendritic cells. J Immunol 169:5424–5432PubMedCrossRefGoogle Scholar
  98. Nollen EA, Morimoto RI (2002) Chaperoning signaling pathways: molecular chaperones as stress-sensing ‘heat shock’ proteins. J Cell Sci 115:2809–2816PubMedGoogle Scholar
  99. O’Neill S, Humphries D, Tse G, Marson LP, Dhaliwal K, Hughes J, Ross JA, Wigmore SJ, Harrison EM (2015) Heat shock protein 90 inhibition abrogates TLR4-mediated NF-kappaB activity and reduces renal ischemia-reperfusion injury. Sci Rep 5:12958PubMedPubMedCentralCrossRefGoogle Scholar
  100. Park JS, Gamboni-Robertson F, He Q, Svetkauskaite D, Kim JY, Strassheim D, Sohn JW, Yamada S, Maruyama I, Banerjee A et al (2006) High mobility group box 1 protein interacts with multiple Toll-like receptors. Am J Phys Cell Phys 290:C917–C924CrossRefGoogle Scholar
  101. Pespeni M, Mackersie RC, Lee H, Morabito D, Hodnett M, Howard M, Pittet JF (2005) Serum levels of Hsp60 correlate with the development of acute lung injury after trauma. J Surg Res 126:41–47PubMedCrossRefGoogle Scholar
  102. Poulaki V, Iliaki E, Mitsiades N, Mitsiades CS, Paulus YN, Bula DV, Gragoudas ES, Miller JW (2007) Inhibition of Hsp90 attenuates inflammation in endotoxin-induced uveitis. FASEB J 21:2113–2123PubMedCrossRefGoogle Scholar
  103. Qazi KR, Torregrosa Paredes P, Dahlberg B, Grunewald J, Eklund A, Gabrielsson S (2010) Proinflammatory exosomes in bronchoalveolar lavage fluid of patients with sarcoidosis. Thorax 65:1016–1024PubMedCrossRefGoogle Scholar
  104. Rajaiya J, Yousuf MA, Singh G, Stanish H, Chodosh J (2012) Heat shock protein 27 mediated signaling in viral infection. Biochemistry 51:5695–5702PubMedPubMedCentralCrossRefGoogle Scholar
  105. Randow F, Seed B (2001) Endoplasmic reticulum chaperone gp96 is required for innate immunity but not cell viability. Nat Cell Biol 3:891–896PubMedCrossRefGoogle Scholar
  106. Raposo G, Nijman HW, Stoorvogel W, Liejendekker R, Harding CV, Melief CJ, Geuze HJ (1996) B lymphocytes secrete antigen-presenting vesicles. J Exp Med 183:1161–1172PubMedCrossRefGoogle Scholar
  107. Rice JW, Veal JM, Fadden RP, Barabasz AF, Partridge JM, Barta TE, Dubois LG, Huang KH, Mabbett SR, Silinski MA et al (2008) Small molecule inhibitors of Hsp90 potently affect inflammatory disease pathways and exhibit activity in models of rheumatoid arthritis. Arthritis Rheum 58:3765–3775PubMedCrossRefGoogle Scholar
  108. Sauter B, Albert ML, Francisco L, Larsson M, Somersan S, Bhardwaj N (2000) Consequences of cell death: exposure to necrotic tumor cells, but not primary tissue cells or apoptotic cells, induces the maturation of immunostimulatory dendritic cells. J Exp Med 191:423–434PubMedPubMedCentralCrossRefGoogle Scholar
  109. Scroggins BT, Robzyk K, Wang D, Marcu MG, Tsutsumi S, Beebe K, Cotter RJ, Felts S, Toft D, Karnitz L et al (2007) An acetylation site in the middle domain of Hsp90 regulates chaperone function. Mol Cell 25:151–159PubMedPubMedCentralCrossRefGoogle Scholar
  110. Shang L, Tomasi TB (2006) The heat shock protein 90-CDC37 chaperone complex is required for signaling by types I and II interferons. J Biol Chem 281:1876–1884PubMedCrossRefGoogle Scholar
  111. Shrestha L, Bolaender A, Patel HJ, Taldone T (2016) Heat shock protein (HSP) drug discovery and development: targeting heat shock proteins in disease. Curr Top Med Chem 16:2753–2764PubMedPubMedCentralCrossRefGoogle Scholar
  112. Sims JD, McCready J, Jay DG (2011) Extracellular heat shock protein (Hsp)70 and Hsp90alpha assist in matrix metalloproteinase-2 activation and breast cancer cell migration and invasion. PLoS One 6:e18848PubMedPubMedCentralCrossRefGoogle Scholar
  113. Singh IS, Gupta A, Nagarsekar A, Cooper Z, Manka C, Hester L, Benjamin IJ, He JR, Hasday JD (2008) Heat shock co-activates interleukin-8 transcription. Am J Respir Cell Mol Biol 39:235–242PubMedPubMedCentralCrossRefGoogle Scholar
  114. Skokos D, Le Panse S, Villa I, Rousselle JC, Peronet R, Namane A, David B, Mecheri S (2001) Nonspecific B and T cell-stimulatory activity mediated by mast cells is associated with exosomes. Int Arch Allergy Immunol 124:133–136PubMedCrossRefGoogle Scholar
  115. Skokos D, Botros HG, Demeure C, Morin J, Peronet R, Birkenmeier G, Boudaly S, Mecheri S (2003) Mast cell-derived exosomes induce phenotypic and functional maturation of dendritic cells and elicit specific immune responses in vivo. J Immunol 170:3037–3045PubMedCrossRefGoogle Scholar
  116. Snyder YM, Guthrie L, Evans GF, Zuckerman SH (1992) Transcriptional inhibition of endotoxin-induced monokine synthesis following heat shock in murine peritoneal macrophages. J Leukoc Biol 51:181–187PubMedCrossRefGoogle Scholar
  117. Soti C, Nagy E, Giricz Z, Vigh L, Csermely P, Ferdinandy P (2005) Heat shock proteins as emerging therapeutic targets. Br J Pharmacol 146:769–780PubMedPubMedCentralCrossRefGoogle Scholar
  118. Srivastava P (2002) Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2:185–194PubMedCrossRefPubMedCentralGoogle Scholar
  119. Takeda K, Akira S (2007) Toll-like receptors. Curr Protoc Immunol Chapter 14:Unit 14.12PubMedGoogle Scholar
  120. Takeuchi T, Suzuki M, Fujikake N, Popiel HA, Kikuchi H, Futaki S, Wada K, Nagai Y (2015) Intercellular chaperone transmission via exosomes contributes to maintenance of protein homeostasis at the organismal level. Proc Natl Acad Sci U S A 112:E2497–E2506PubMedPubMedCentralCrossRefGoogle Scholar
  121. Tang D, Kang R, Coyne CB, Zeh HJ, Lotze MT (2012) PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev 249:158–175PubMedPubMedCentralCrossRefGoogle Scholar
  122. Thery C, Boussac M, Veron P, Ricciardi-Castagnoli P, Raposo G, Garin J, Amigorena S (2001) Proteomic analysis of dendritic cell-derived exosomes: a secreted subcellular compartment distinct from apoptotic vesicles. J Immunol 166:7309–7318PubMedCrossRefGoogle Scholar
  123. Tobian AA, Canaday DH, Boom WH, Harding CV (2004) Bacterial heat shock proteins promote CD91-dependent class I MHC cross-presentation of chaperoned peptide to CD8+ T cells by cytosolic mechanisms in dendritic cells versus vacuolar mechanisms in macrophages. J Immunol 172:5277–5286PubMedCrossRefGoogle Scholar
  124. Toldo S, Quader M, Salloum FN, Mezzaroma E, Abbate A (2016) Targeting the innate immune response to improve cardiac graft recovery after heart transplantation: implications for the donation after cardiac death. Int J Mol Sci 17:E958PubMedCrossRefGoogle Scholar
  125. Triantafilou M, Triantafilou K (2004) Heat-shock protein 70 and heat-shock protein 90 associate with Toll-like receptor 4 in response to bacterial lipopolysaccharide. Biochem Soc Trans 32:636–639PubMedCrossRefPubMedCentralGoogle Scholar
  126. Tukaj S, Zillikens D, Kasperkiewicz M (2014) Inhibitory effects of heat shock protein 90 blockade on proinflammatory human Th1 and Th17 cell subpopulations. J Inflamm (Lond) 11:10CrossRefGoogle Scholar
  127. Valadi H, Ekstrom K, Bossios A, Sjostrand M, Lee JJ, Lotvall JO (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9:654–659PubMedPubMedCentralCrossRefGoogle Scholar
  128. Vega VL, Rodriguez-Silva M, Frey T, Gehrmann M, Diaz JC, Steinem C, Multhoff G, Arispe N, De Maio A (2008) Hsp70 translocates into the plasma membrane after stress and is released into the extracellular environment in a membrane-associated form that activates macrophages. J Immunol 180:4299–4307PubMedCrossRefGoogle Scholar
  129. Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature 412:346–351PubMedCrossRefGoogle Scholar
  130. Wang YL, Shen HH, Cheng PY, Chu YJ, Hwang HR, Lam KK, Lee YM (2016) 17-DMAG, an HSP90 inhibitor, ameliorates multiple organ dysfunction syndrome via induction of HSP70 in Endotoxemic rats. PLoS One 11:e0155583PubMedPubMedCentralCrossRefGoogle Scholar
  131. Wax S, Piecyk M, Maritim B, Anderson P (2003) Geldanamycin inhibits the production of inflammatory cytokines in activated macrophages by reducing the stability and translation of cytokine transcripts. Arthritis Rheum 48:541–550PubMedCrossRefGoogle Scholar
  132. Wei D, Li NL, Zeng Y, Liu B, Kumthip K, Wang TT, Huo D, Ingels JF, Lu L, Shang J et al (2016) The molecular chaperone GRP78 contributes to toll-like receptor 3-mediated innate immune response to hepatitis C virus in hepatocytes. J Biol Chem 291:12294–12309PubMedPubMedCentralCrossRefGoogle Scholar
  133. Wolfers J, Lozier A, Raposo G, Regnault A, Thery C, Masurier C, Flament C, Pouzieux S, Faure F, Tursz T et al (2001) Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat Med 7:297–303PubMedCrossRefGoogle Scholar
  134. Woronicz JD, Gao X, Cao Z, Rothe M, Goeddel DV (1997) IkappaB kinase-beta: NF-kappaB activation and complex formation with IkappaB kinase-alpha and NIK. Science 278:866–869PubMedCrossRefGoogle Scholar
  135. Wree A, Mehal WZ, Feldstein AE (2016) Targeting cell death and sterile inflammation loop for the treatment of nonalcoholic steatohepatitis. Semin Liver Dis 36:27–36PubMedPubMedCentralCrossRefGoogle Scholar
  136. Xie Y, Chen C, Stevenson MA, Auron PE, Calderwood SK (2002) Heat shock factor 1 represses transcription of the IL-1beta gene through physical interaction with the nuclear factor of interleukin 6. J Biol Chem 277:11802–11810PubMedCrossRefGoogle Scholar
  137. Yang RC, Wang CI, Chen HW, Chou FP, Lue SI, Hwang KP (1998) Heat shock treatment decreases the mortality of sepsis in rats. Kaohsiung J Med Sci 14:664–672PubMedGoogle Scholar
  138. Yang K, Shi H, Qi R, Sun S, Tang Y, Zhang B, Wang C (2006) Hsp90 regulates activation of interferon regulatory factor 3 and TBK-1 stabilization in Sendai virus-infected cells. Mol Biol Cell 17:1461–1471PubMedPubMedCentralCrossRefGoogle Scholar
  139. Yang Y, Liu B, Dai J, Srivastava PK, Zammit DJ, Lefrancois L, Li Z (2007) Heat shock protein gp96 is a master chaperone for toll-like receptors and is important in the innate function of macrophages. Immunity 26:215–226PubMedPubMedCentralCrossRefGoogle Scholar
  140. Zheng H, Dai J, Stoilova D, Li Z (2001) Cell surface targeting of heat shock protein gp96 induces dendritic cell maturation and antitumor immunity. J Immunol 167:6731–6735PubMedCrossRefGoogle Scholar
  141. Zheng Y, Gardner SE, Clarke MC (2011) Cell death, damage-associated molecular patterns, and sterile inflammation in cardiovascular disease. Arterioscler Thromb Vasc Biol 31:2781–2786PubMedCrossRefGoogle Scholar
  142. Zhu FG, Pisetsky DS (2001) Role of the heat shock protein 90 in immune response stimulation by bacterial DNA and synthetic oligonucleotides. Infect Immun 69:5546–5552PubMedPubMedCentralCrossRefGoogle Scholar
  143. Zitvogel L, Regnault A, Lozier A, Wolfers J, Flament C, Tenza D, Ricciardi-Castagnoli P, Raposo G, Amigorena S (1998) Eradication of established murine tumors using a novel cell-free vaccine: dendritic cell-derived exosomes. Nat Med 4:594–600PubMedCrossRefGoogle Scholar
  144. Zou N, Ao L, Cleveland JC Jr, Yang X, Su X, Cai GY, Banerjee A, Fullerton DA, Meng X (2008) Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion. Am J Physiol Heart Circ Physiol 294:H2805–H2813PubMedPubMedCentralCrossRefGoogle Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA

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