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Extracellular Vesicle-Associated Moonlighting Proteins: Heat Shock Proteins and Metalloproteinases

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Heat Shock Proteins in Inflammatory Diseases

Part of the book series: Heat Shock Proteins ((HESP,volume 22))

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Abbreviations

APC:

antigen-presenting cell

ATP:

adenosine triphosphate

B:

B lymphocyte

BBB:

blood-brain barrier

CCL:

C-C motif chemokine ligand

CRPC:

castration-resistant prostate cancer

DAMP:

damage-associated molecular pattern

DC:

dendritic cell

ECM:

extracellular matrix

EV:

extracellular vesicle

HA:

hyaluronan

HMGB:

high-mobility group protein with a ‘Box’ domain

HSP:

heat shock protein

IL:

interleukin

IL-1R:

interleukin 1 receptor

L-EV:

large extracellular vesicle

LRP1:

low-density lipoprotein receptor-related protein 1

MAPK:

microtubule associated protein kinase

MEV:

metastatic oral cancer-derived extracellular vesicle

MHC:

major histocompatibility complex

MMP:

matrix metalloproteinase

Mφ:

macrophages

NALP3:

NACHT, LRR and PYD domains-containing protein 3

NK:

natural killer

NLR:

nucleotide-binding leucine-rich repeat

NLS:

nuclear localization signal

NOD:

nucleotide-binding oligomerization domain

OA:

osteoarthritis

OSCC:

oral squamous cell carcinoma

P2:

purinergic type 2 receptor

PAMP:

pathogen-associated molecular pattern

PC-3:

prostate cancer

PI3K/AKT:

phosphatidylinositol 3-kinase and protein kinase B

PRR:

pattern recognition receptor

PTM:

post-translational modification

RA:

rheumatoid arthritis

RAGE:

receptor for advanced glycation end-products

RASF:

rheumatoid arthritis synovial fluid

SASP:

senescence-associated secretory phenotype

s-EV:

small extracellular vesicle

SR:

scavenger receptor

SRA1:

steroid receptor RNA activator 1

SREC-1:

scavenger receptor expressed by endothelial cells-I

T:

T lymphocyte

TLR:

toll-like receptor

Treg:

regulatory T cell

References

  1. Abubucker S, Segata N, Goll J, Schubert AM, Izard J, Cantarel BL et al (2015) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 7(2):1–9. https://doi.org/10.1016/j.molcel.2012.08.033

    Article  CAS  Google Scholar 

  2. Aoshiba K, Tsuji T, Kameyama S, Itoh M, Semba S, Yamaguchi K, Nakamura H (2013) Senescence-associated secretory phenotype in a mouse model of bleomycin-induced lung injury. Exp Toxicol Pathol 65(7–8):1053–1062. https://doi.org/10.1016/j.etp.2013.04.001

    Article  CAS  PubMed  Google Scholar 

  3. Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW et al (2000) HSP70 stimulates cytokine production through a CD 14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6(4):435–442. https://doi.org/10.1038/74697

    Article  CAS  PubMed  Google Scholar 

  4. 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(3):303–313. https://doi.org/10.1016/S1074-7613(01)00111-X

    Article  CAS  PubMed  Google Scholar 

  5. Becker T, Hartl F-U, Wieland F (2002) CD40, an extracellular receptor for binding and uptake of Hsp70-peptide complexes. J Cell Biol 158(7):1277–1285. https://doi.org/10.1083/jcb.200208083

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ben-Sasson SZ, Hu-Li J, Quiel J, Cauchetaux S, Ratner M, Shapira I et al (2009) IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A 106(17):7119–7124. https://doi.org/10.1073/pnas.0902745106

    Article  PubMed  PubMed Central  Google Scholar 

  7. Bendz H, Marincek BC, Momburg F, Ellwart JW, Issels RD, Nelson PJ, Noessner E (2008) Calcium signaling in dendritic cells by human or mycobacterial Hsp70 is caused by contamination and is not required for Hsp70-mediated enhancement of cross-presentation. J Biol Chem 283(39):26477–26483. https://doi.org/10.1074/jbc.M803310200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Berwin B, Hart JP, Rice S, Gass C, Pizzo SV, Post SR, Nicchitta CV (2003) Scavenger receptor-A mediates gp96/GRP94 and calreticulin internalization by antigen-presenting cells. EMBO J 22(22):6127–6136. https://doi.org/10.1093/emboj/cdg572

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Bethke K, Staib F, Distler M, Schmitt U, Jonuleit H, Enk AH et al (2002) Different efficiency of heat shock proteins (HSP) to activate human monocytes and dendritic cells: superiority of HSP60. J Immunol 169(11):6141–6148. https://doi.org/10.4049/jimmunol.169.11.6141

    Article  CAS  PubMed  Google Scholar 

  10. Bianchi ME (2007) DAMPs, PAMPs and alarmins: all we need to know about danger. J Leukoc Biol 81(1):1–5. https://doi.org/10.1189/jlb.0306164

    Article  CAS  PubMed  Google Scholar 

  11. Brooks PC, Silletti S, von Schalscha TL, Friedlander M, Cheresh DA (1998) Disruption of angiogenesis by PEX, a noncatalytic metalloproteinase fragment with integrin binding activity. Cell 92(3):391–400. https://doi.org/10.1016/s0092-8674(00)80931-9

    Article  CAS  PubMed  Google Scholar 

  12. Bukau B, Weissman J, Horwich A (2006) Molecular chaperones and protein quality control. Cell 125(3):443–451. https://doi.org/10.1016/j.cell.2006.04.014

    Article  CAS  PubMed  Google Scholar 

  13. Campisi J (2013) Aging, cellular senescence, and cancer. Annu Rev Physiol 75(1):685–705. https://doi.org/10.1146/annurev-physiol-030212-183653

    Article  CAS  PubMed  Google Scholar 

  14. Castiglioni A, Canti V, Rovere-Querini P, Manfredi AA (2011) High-mobility group box 1 (HMGB1) as a master regulator of innate immunity. Cell Tissue Res 343(1):189–199. https://doi.org/10.1007/s00441-010-1033-1

    Article  CAS  PubMed  Google Scholar 

  15. Celis L, Vandevyver C, Geusens P, Dequeker J, Raus J, Zhang J (1997) Clonal expansion of mycobacterial heat-shock protein-reactive T lymphocytes in the synovial fluid and blood of rheumatoid arthritis patients. Arthritis Rheum 40(3):510–519. https://doi.org/10.1002/art.1780400317

    Article  CAS  PubMed  Google Scholar 

  16. Chan JK, Roth J, Oppenheim JJ, Tracey KJ, Vogl T, Feldmann M et al (2012) Alarmins: awaiting a clinical response. J Clin Invest 122(8):2711–2719. https://doi.org/10.1172/JCI62423

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen C, Jeffery C (2019) Moonlighting functions of heat shock protein 90. In: Kaur P, Asea AAA (eds) Heat shock protein 90 in human diseases and disorders, 19th edn. Springer, Cham. https://doi.org/10.1007/978-3-030-23158-3_13

    Chapter  Google Scholar 

  18. Chen GY, Tang J, Zheng P, Liu Y (2009) CD24 and siglec-10 selectively repress tissue damage – induced immune responses. Science 323(5922):1722–1725. https://doi.org/10.1126/science.1168988

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ciocca DR, Calderwood SK (2005, June) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10:86–103. https://doi.org/10.1379/CSC-99r.1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Das N, Dewan V, Grace PM, Gunn RJ, Tamura R, Tzarum N et al (2016) HMGB1 activates proinflammatory signaling via TLR5 leading to allodynia. Cell Rep 17(4):1128–1140. https://doi.org/10.1016/j.celrep.2016.09.076

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. de Kleer IM, Wedderburn LR, Taams LS, Patel A, Varsani H, Klein M et al (2004) CD4 + CD25 bright regulatory T cells actively regulate inflammation in the joints of patients with the remitting form of juvenile idiopathic arthritis. J Immunol 172(10):6435–6443. https://doi.org/10.4049/jimmunol.172.10.6435

    Article  PubMed  Google Scholar 

  22. Delneste Y (2004) Scavenger receptors and heat-shock protein-mediated antigen cross-presentation. Biochem Soc Trans 32(4):633–635. https://doi.org/10.1042/BST0320633

    Article  CAS  PubMed  Google Scholar 

  23. Dinarello CA (1994) The biological properties of interleukin-1. Eur Cytokine Netw 5:517–531

    CAS  PubMed  Google Scholar 

  24. Dreiza CM, Komalavilas P, Furnish EJ, Flynn CR, Sheller MR, Smoke CC et al (2010) The small heat shock protein, HSPB6, in muscle function and disease. Cell Stress Chaperones 15:1–11. https://doi.org/10.1007/s12192-009-0127-8

    Article  CAS  PubMed  Google Scholar 

  25. Dumitriu IE, Baruah P, Bianchi ME, Manfredi AA, Rovere-Querini P (2005) Requirement of HMGB1 and RAGE for the maturation of human plasmacytoid dendritic cells. Eur J Immunol 35(7):2184–2190. https://doi.org/10.1002/eji.200526066

    Article  CAS  PubMed  Google Scholar 

  26. Eguchi T, Lang BJ, Murshid A, Prince T, Gong J, Calderwood SK (2018) Regulatory roles for Hsp70 in cancer incidence and tumor progression. In: Role of molecular chaperones in structural folding, biological functions, and drug interactions of client proteins: frontiers in structural biology, vol 1. Bentham Science Publishers Ltd, Sharjah, pp 1–22. https://doi.org/10.2174/9781681086156118010003

    Chapter  Google Scholar 

  27. Eguchi T, Ono K, Kawata K, Okamoto K, Calderwood SK (2019) Regulatory roles of HSP90-rich extracellular vesicles. In: Kaur P, Asea AAA (eds) Heat shock protein 90 in human diseases and disorders, 19th edn. https://doi.org/10.1007/978-3-030-23158-3_1

    Chapter  Google Scholar 

  28. Eguchi T, Calderwood SK, Takigawa M, Kubota S, Kozaki KI (2017) Intracellular MMP3 promotes HSP gene expression in collaboration with chromobox proteins. J Cell Biochem 118(1):43–51. https://doi.org/10.1002/jcb.25607

    Article  CAS  PubMed  Google Scholar 

  29. Eguchi T, Kubota S, Kawata K, Mukudai Y, Uehara J, Ohgawara T et al (2008) Novel transcription-factor-like function of human matrix metalloproteinase 3 regulating the CTGF/CCN2 gene. Mol Cell Biol 28(7):255–264. https://doi.org/10.1128/MCB.01288-07

    Article  CAS  Google Scholar 

  30. Eguchi T, Kubota S, Kawata K, Mukudai Y, Uehara J, Ohgawara T et al (2010) Novel transcriptional regulation of CCN2/CTGF by nuclear translocation of MMP3. In: CCN proteins in health and disease, pp 255–264. https://doi.org/10.1007/978-90-481-3779-4_19

    Chapter  Google Scholar 

  31. Eguchi T, Sogawa C, Ono K, Matsumoto M, Tran MT, Okusha Y et al (2020) Cell stress induced Stressome release including damaged membrane vesicles and extracellular HSP90 by prostate cancer cells. Cells 9(3):755. https://doi.org/10.3390/cells9030755

    Article  CAS  PubMed Central  Google Scholar 

  32. Ehrchen JM, Sunderkötter C, Foell D, Vogl T, Roth J (2009) The endogenous toll-like receptor 4 agonist S100A8/S100A9 (calprotectin) as innate amplifier of infection, autoimmunity, and cancer. J Leukoc Biol 86(3):557–566. https://doi.org/10.1189/jlb.1008647

    Article  CAS  PubMed  Google Scholar 

  33. Fadda S, Abolkheir E, Afifi R, Gamal M (2016) Serum matrix metalloproteinase-3 in rheumatoid arthritis patients: correlation with disease activity and joint destruction. Egypt Rheumatol 38(3):153–159. https://doi.org/10.1016/j.ejr.2016.01.001

    Article  Google Scholar 

  34. Foell D, Wittkowski H, Roth J (2007, July) Mechanisms of disease: a “DAMP” view of inflammatory arthritis. Nat Clin Pract Rheumatol 3:382–390. https://doi.org/10.1038/ncprheum0531

    Article  CAS  PubMed  Google Scholar 

  35. Panayi GS, Corrigal VM (2003) Heat shock proteins and rheumatoid arthritis. In: van W Eden, D. of Immunology, D. of I. D. and Immunology, F. of V. Medicine, U. of Utrecht, Y. … T. Netherlands (ed) Heat shock proteins and inflammation. Birkhäuser, Basel, pp 109–137. https://doi.org/10.1007/978-3-0348-8028-2

    Chapter  Google Scholar 

  36. Gastpar R, Gross C, Rossbacher L, Ellwart J, Riegger J, Multhoff G (2004) The cell surface-localized heat shock protein 70 epitope TKD induces migration and Cytolytic activity selectively in human NK cells. J Immunol 172(2):972–980. https://doi.org/10.4049/jimmunol.172.2.972

    Article  CAS  PubMed  Google Scholar 

  37. Gorgoulis V, Adams PD, Alimonti A, Bennett DC, Bischof O, Bishop C et al (2019, October 31) Cellular senescence: defining a path forward. Cell 179:813–827. https://doi.org/10.1016/j.cell.2019.10.005

    Article  CAS  PubMed  Google Scholar 

  38. Gu L, Kitamura M (2012) Sensitive detection and monitoring of senescence-associated secretory phenotype by SASP-RAP assay. PLoS One 7(12). https://doi.org/10.1371/journal.pone.0052305

  39. Bausinger H, Lipsker D, Ziylan U, Manie S, Briand J-P, Cazenave J-P et al (2002) Endotoxin-free heat-shock protein 70 fails to induce APC activation. Eur J Immunol 32(12):3708–3713. https://doi.org/10.1002/1521-4141(200212)32:12<3708::AID-IMMU3708>3.0.CO;2-C

    Article  CAS  PubMed  Google Scholar 

  40. Harris HE, Raucci A (2006) Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep 7(8):774–778. https://doi.org/10.1038/sj.embor.7400759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Hashiramoto A, Murata M, Kawazoe T, Yoshida K, Akiyama C, Shiozawa K, Shiozawa S (2011) Heat shock protein 90 maintains the tumour-like character of rheumatoid synovial cells by stabilizing integrin-linked kinase, extracellular signal-regulated kinase and protein kinase B. Rheumatology (Oxford) 50(5):852–861. https://doi.org/10.1093/rheumatology/keq385

    Article  CAS  Google Scholar 

  42. Hassona Y, Cirillo N, Heesom K, Parkinson EK, Prime SS (2014) Senescent cancer-associated fibroblasts secrete active MMP-2 that promotes keratinocyte dis-cohesion and invasion. Br J Cancer 111(6):1230–1237. https://doi.org/10.1038/bjc.2014.438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Haynes SE, Hollopeter G, Yang G, Kurpius D, Dailey ME, Gan WB, Julius D (2006) The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat Neurosci 9(12):1512–1519. https://doi.org/10.1038/nn1805

    Article  CAS  PubMed  Google Scholar 

  44. Higginbotham JN, Demory Beckler M, Gephart JD, Franklin JL, Bogatcheva G, Kremers GJ et al (2011) Amphiregulin exosomes increase cancer cell invasion. Curr Biol 21(9):779–786. https://doi.org/10.1016/j.cub.2011.03.043

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Horvath RJ, DeLeo JA (2009) Morphine enhances microglial migration through modulation of P2X 4 receptor signaling. J Neurosci 29(4):998–1005. https://doi.org/10.1523/JNEUROSCI.4595-08.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Huang Q-Q, Sobkoviak R, Jockheck-Clark AR, Shi B, Mandelin AM, Tak PP et al (2009) Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 Signaling. J Immunol 182(8):4965–4973. https://doi.org/10.4049/jimmunol.0801563

    Article  CAS  PubMed  Google Scholar 

  47. Iwahashi M, Yamamura M, Aita T, Okamoto A, Ueno A, Ogawa N et al (2004) Expression of toll-like receptor 2 on CD16+ blood monocytes and synovial tissue macrophages in rheumatoid arthritis. Arthritis Rheum 50(5):1457–1467. https://doi.org/10.1002/art.20219

    Article  CAS  PubMed  Google Scholar 

  48. Jeffery CJ (1999) Moonlighting proteins. Trends Biochem Sci 24:8–11. https://doi.org/10.1016/S0968-0004(98)01335-8

    Article  CAS  PubMed  Google Scholar 

  49. Jeffery CJ (2016) Protein species and moonlighting proteins: very small changes in a protein’s covalent structure can change its biochemical function. J Proteome 134:19–24. https://doi.org/10.1016/j.jprot.2015.10.003

    Article  CAS  Google Scholar 

  50. Jeffery CJ (2018) Protein moonlighting: what is it, and why is it important? Philos Trans R Soc B Biol Sci 373:20160523. https://doi.org/10.1098/rstb.2016.0523

    Article  CAS  Google Scholar 

  51. Jiang D, Liang J, Fan J, Yu S, Chen S, Luo Y et al (2005) Regulation of lung injury and repair by toll-like receptors and hyaluronan. Nat Med 11(11):1173–1179. https://doi.org/10.1038/nm1315

    Article  CAS  PubMed  Google Scholar 

  52. Jobin PG, Butler GS, Overall CM (2017) New intracellular activities of matrix metalloproteinases shine in the moonlight. Biochim Biophys Acta, Mol Cell Res 1864:2043–2055. https://doi.org/10.1016/j.bbamcr.2017.05.013

    Article  CAS  Google Scholar 

  53. Kamphuis S, Kuis W, De Jager W, Teklenburg G, Massa M, Gordon G et al (2005) Tolerogenic immune responses to novel T-cell epitopes from heat-shock protein 60 in juvenile idiopathic arthritis. Lancet 366(9479):50–56. https://doi.org/10.1016/S0140-6736(05)66827-4

    Article  CAS  PubMed  Google Scholar 

  54. Kerkhoff C, Radon Y, Flaßkamp H (2014) Alarmins. In: Encyclopedia of inflammatory diseases, pp 1–12. https://doi.org/10.1007/978-3-0348-0620-6_78-1

    Chapter  Google Scholar 

  55. Khalil AA, Kabapy NF, Deraz SF, Smith C (2011) Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets? Biochim Biophys Acta Rev Cancer 1816:89–104. https://doi.org/10.1016/j.bbcan.2011.05.001

    Article  CAS  Google Scholar 

  56. Kol A, Lichtman AH, Finberg RW, Libby P, Kurt-Jones EA (2000) Cutting edge: heat shock protein (HSP) 60 activates the innate immune response: CD14 is an essential receptor for HSP60 activation of mononuclear cells. J Immunol 164(1):13–17. https://doi.org/10.4049/jimmunol.164.1.13

    Article  CAS  PubMed  Google Scholar 

  57. Kondo S (2002) Connective tissue growth factor increased by hypoxia may initiate angiogenesis in collaboration with matrix metalloproteinases. Carcinogenesis 23(5):769–776. https://doi.org/10.1093/carcin/23.5.769

    Article  CAS  PubMed  Google Scholar 

  58. Kriegenburg F, Ellgaard L, Hartmann-Petersen R (2012) Molecular chaperones in targeting misfolded proteins for ubiquitin-dependent degradation. FEBS J 279:532–542. https://doi.org/10.1111/j.1742-4658.2011.08456.x

    Article  CAS  PubMed  Google Scholar 

  59. Kwan JA, Schulze CJ, Wang W, Leon H, Sariahmetoglu M, Sung M et al (2004) Matrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro. FASEB J 18(6):690–692. https://doi.org/10.1096/fj.02-1202fje

    Article  CAS  PubMed  Google Scholar 

  60. Lavric M, Miranda-García MA, Holzinger D, Foell D, Wittkowski H (2017) Alarmins firing arthritis: helpful diagnostic tools and promising therapeutic targets. Joint Bone Spine 84(4):401–410. https://doi.org/10.1016/j.jbspin.2016.06.010

    Article  CAS  PubMed  Google Scholar 

  61. Lewthwaite JC, Coates ARM, Tormay P, Singh M, Mascagni P, Poole S et al (2001) Mycobacterium tuberculosis chaperonin 60.1 is a more potent cytokine stimulator than chaperonin 60.2 (Hsp 65) and contains a CD14-binding domain. Infect Immun 69(12):7349–7355. https://doi.org/10.1128/IAI.69.12.7349-7355.2001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Lim H, Park H, Kim HP (2015) Effects of flavonoids on senescence-associated secretory phenotype formation from bleomycin-induced senescence in BJ fibroblasts. Biochem Pharmacol 96(4):337–348. https://doi.org/10.1016/j.bcp.2015.06.013

    Article  CAS  PubMed  Google Scholar 

  63. Liu-Bryan R, Terkeltaub R (2015) Emerging regulators of the inflammatory process in osteoarthritis. Nat Rev Rheumatol 11(1):35–44. https://doi.org/10.1038/nrrheum.2014.162

    Article  CAS  PubMed  Google Scholar 

  64. Loeser RF, Goldring SR, Scanzello CR, Goldring MB (2012) Osteoarthritis: a disease of the joint as an organ. Arthritis Rheum 64(6):1697–1707. https://doi.org/10.1002/art.34453

    Article  PubMed  PubMed Central  Google Scholar 

  65. Ma J-D, Zhou J-J, Zheng D-H, Chen L-F, Mo Y-Q, Wei X et al (2014) Serum matrix metalloproteinase-3 as a noninvasive biomarker of histological synovitis for diagnosis of rheumatoid arthritis. Mediat Inflamm 2014:179284. https://doi.org/10.1155/2014/179284

    Article  CAS  Google Scholar 

  66. Macario AJL, De Macario EC (2007) Molecular chaperones: multiple functions, pathologies, and potential applications. Front Biosci 12(7):2588–2600. https://doi.org/10.2741/2257

    Article  CAS  PubMed  Google Scholar 

  67. Mani M, Chen C, Amblee V, Liu H, Mathur T, Zwicke G et al (2014) MoonProt: a database for proteins that are known to moonlight. Nucleic Acids Res 43:277–282. https://doi.org/10.1093/nar/gku954

    Article  CAS  Google Scholar 

  68. Marchant DJ, Bellac CL, Moraes TJ, Wadsworth SJ, Dufour A, Butler GS et al (2014) A new transcriptional role for matrix metalloproteinase-12 in antiviral immunity. Nat Med 20(5):493–502. https://doi.org/10.1038/nm.3508

    Article  CAS  PubMed  Google Scholar 

  69. Martin CA, Carsons SE, Kowalewski R, Bernstein D, Valentino M, Santiago-Schwarz F (2003) Aberrant extracellular and dendritic cell (DC) surface expression of heat shock protein (hsp)70 in the rheumatoid joint: possible mechanisms of hsp/DC-mediated cross-priming. J Immunol 171(11):5736–5742. https://doi.org/10.4049/jimmunol.171.11.5736

    Article  CAS  PubMed  Google Scholar 

  70. Martinon F, Petrilli V, Mayor A, Tardivel A, Tschopp J (2006) Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440(7081):237–241. https://doi.org/10.1038/nature04516

    Article  CAS  PubMed  Google Scholar 

  71. Massa M, Passalia M, Manzoni SM, Campanelli R, Ciardelli L, Yung GP et al (2007) Differential recognition of heat-shock protein dnaJ-derived epitopes by effector and Treg cells leads to modulation of inflammation in juvenile idiopathic arthritis. Arthritis Rheum 56(5):1648–1657. https://doi.org/10.1002/art.22567

    Article  CAS  PubMed  Google Scholar 

  72. Müller T, Robaye B, Vieira RP, Ferrari D, Grimm M, Jakob T et al (2010) The purinergic receptor P2Y2 receptor mediates chemotaxis of dendritic cells and eosinophils in allergic lung inflammation. Allergy Eur J Allergy Clin Immunol 65(12):1545–1553. https://doi.org/10.1111/j.1398-9995.2010.02426.x

    Article  CAS  Google Scholar 

  73. Murshid A, Gong J, Calderwood SK (2010) Heat shock protein 90 mediates efficient antigen cross presentation through the scavenger receptor expressed by endothelial cells-I. J Immunol 185(5):2903–2917. https://doi.org/10.4049/jimmunol.0903635

    Article  CAS  PubMed  Google Scholar 

  74. Murshid A, Gong J, Calderwood SK (2012) The role of heat shock proteins in antigen cross presentation. Front Immunol 3:63. https://doi.org/10.3389/fimmu.2012.00063

    Article  PubMed  PubMed Central  Google Scholar 

  75. Murshid A, Gong J, Calderwood SK (2014) Hsp90-peptide complexes stimulate antigen presentation through the class II pathway after binding scavenger receptor SREC-I. Immunobiology 219(12):924–931. https://doi.org/10.1016/j.imbio.2014.08.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Nakae S, Naruse-Nakajima C, Sudo K, Horai R, Asano M, Iwakura Y (2001) IL-1α, but not IL-1β, is required for contact-allergen-specific T cell activation during the sensitization phase in contact hypersensitivity. Int Immunol 13(12):1471–1478. https://doi.org/10.1093/intimm/13.12.1471

    Article  CAS  PubMed  Google Scholar 

  77. Nefla M, Holzinger D, Berenbaum F, Jacques C (2016) The danger from within: Alarmins in arthritis. Nat Rev Rheumatol 12(11):669–683. https://doi.org/10.1038/nrrheum.2016.162

    Article  CAS  PubMed  Google Scholar 

  78. Okusha Y, Eguchi T, Sogawa C, Okui T, Nakano K, Okamoto K et al (2018) The intranuclear PEX domain of MMP involves proliferation, migration, and metastasis of aggressive adenocarcinoma cells. J Cell Biochem 119:(April), 1–(April),14. https://doi.org/10.1002/jcb.27040

    Article  CAS  Google Scholar 

  79. Okusha Y, Eguchi T, Tran MT, Sogawa C, Yoshida K, Itagaki M et al (2020) Extracellular vesicles enriched with moonlighting metalloproteinase are highly transmissive, pro-tumorigenic, and trans-activates cellular communication network factor (Ccn2/ctgf): CRISPR against cancer. Cancers 12(4):1–27. https://doi.org/10.3390/cancers12040881

    Article  CAS  Google Scholar 

  80. Ono K, Eguchi T, Sogawa C, Calderwood SK, Futagawa J, Kasai T et al (2018) HSP-enriched properties of extracellular vesicles involve survival of metastatic oral cancer cells. J Cell Biochem 119(9):7350–7362. https://doi.org/10.1002/jcb.27039

    Article  CAS  PubMed  Google Scholar 

  81. Ono K, Sogawa C, Kawai H, Tran MT, Taha EA, Lu Y et al (2020) Triple knockdown of CDC37, HSP90-alpha, and HSP90-beta diminishes extracellular vesicles-driven malignancy events and macrophage M2 polarization in oral cancer. J Extracell Vesicles 9:1769373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Oppenheim JJ, Yang D (2005) Alarmins: chemotactic activators of immune responses. Curr Opin Immunol 17(4):359–365. https://doi.org/10.1016/j.coi.2005.06.002

    Article  CAS  PubMed  Google Scholar 

  83. Page-McCaw A, Ewald AJ, Werb Z (2007, March) Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol 8:221–233. https://doi.org/10.1038/nrm2125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Park JS, Svetkauskaite D, He Q, Kim JY, Strassheim D, Ishizaka A, Abraham E (2004) Involvement of toll-like receptors 2 and 4 in cellular activation by high mobility group box 1 protein. J Biol Chem 279(9):7370–7377. https://doi.org/10.1074/jbc.M306793200

    Article  CAS  PubMed  Google Scholar 

  85. Pearl LH (2016) Review: the HSP90 molecular chaperone – an enigmatic ATPase. Biopolymers 105:594–607. https://doi.org/10.1002/bip.22835

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Prakken BJ, Roord S, Van Kooten PJS, Wagenaar JPA, Van Eden W, Albani S, Wauben MHM (2002) Inhibition of adjuvant-induced arthritis by interleukin-10-driven regulatory cells induced via nasal administration of a peptide analog of an arthritis-related heat-shock protein 60 T cell epitope. Arthritis Rheum 46(7):1937–1946. https://doi.org/10.1002/art.10366

    Article  CAS  PubMed  Google Scholar 

  87. Prakken BJ, Samodal R, Le TD, Giannoni F, Yung GP, Scavulli J et al (2004) Epitope-specific immunotherapy induces immune deviation of proinflammatory T cells in rheumatoid arthritis. Proc Natl Acad Sci U S A 101(12):4228–4233. https://doi.org/10.1073/pnas.0400061101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Przybysz M, Borysewicz K, Katnik-Prastowska I (2013) Fibronectin molecular status determination useful to differentiate between rheumatoid arthritis and systemic lupus erythematosus patients. Rheumatol Int 33(1):37–43. https://doi.org/10.1007/s00296-011-2269-0

    Article  CAS  PubMed  Google Scholar 

  89. Rak J, Guha A (2012) Extracellular vesicles – vehicles that spread cancer genes. BioEssays 34(6):489–497. https://doi.org/10.1002/bies.201100169

    Article  CAS  PubMed  Google Scholar 

  90. Ramteke A, Ting H, Agarwal C, Mateen S, Somasagara R, Hussain A et al (2015) Exosomes secreted under hypoxia enhance invasiveness and stemness of prostate cancer cells by targeting adherens junction molecules. Mol Carcinog 54(7):554–565. https://doi.org/10.1002/mc.22124

    Article  CAS  PubMed  Google Scholar 

  91. Rappa F, Farina F, Zummo G, David S, Campanella C, Carini F et al (2012) HSP-Molecular chaperones in cancer biogenesis and tumor therapy: an overview. Anticancer Res 32(12):5139–5150

    CAS  PubMed  Google Scholar 

  92. Roelofs MF, Boelens WC, Joosten LAB, Abdollahi-Roodsaz S, Geurts J, Wunderink LU et al (2006) Identification of small heat shock protein B8 (HSP22) as a novel TLR4 ligand and potential involvement in the pathogenesis of rheumatoid arthritis. J Immunol 176(11):7021–7027. https://doi.org/10.4049/jimmunol.176.11.7021

    Article  CAS  PubMed  Google Scholar 

  93. Rosin DL, Okusa MD (2011) Dangers within: DAMP responses to damage and cell death in kidney disease. J Am Soc Nephrol 22(3):416–425. https://doi.org/10.1681/ASN.2010040430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Ryckman C, Vandal K, Rouleau P, Talbot M, Tessier PA (2003) Proinflammatory activities of S100: proteins S100A8, S100A9, and S100A8/A9 induce neutrophil chemotaxis and adhesion. J Immunol 170(6):3233–3242. https://doi.org/10.4049/jimmunol.170.6.3233

    Article  CAS  PubMed  Google Scholar 

  95. Santos-Junior V d A, Lollo PCB, Cantero MA, Moura CS, Amaya-Farfan J, Morato PN (2018) Heat shock proteins: protection and potential biomarkers for ischemic injury of cardiomyocytes after surgery. Braz J Cardiovasc Surg 33:291–302. https://doi.org/10.21470/1678-9741-2017-0169

    Article  PubMed  PubMed Central  Google Scholar 

  96. Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK et al (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23(5):479–490. https://doi.org/10.1016/j.immuni.2005.09.015

    Article  CAS  PubMed  Google Scholar 

  97. Schopf FH, Biebl MM, Buchner J (2017, June 1) The HSP90 chaperone machinery. Nat Rev Mol Cell Biol 18:345–360. https://doi.org/10.1038/nrm.2017.20

    Article  CAS  PubMed  Google Scholar 

  98. Shekhawat SD, Purohit HJ, Taori GM, Daginawala HF, Kashyap RS (2016) Evaluation of host Hsp(s) as potential biomarkers for the diagnosis of tuberculous meningitis. Clin Neurol Neurosurg 140:47–51. https://doi.org/10.1016/j.clineuro.2015.11.008

    Article  PubMed  Google Scholar 

  99. Siebuhr AS, Kjelgaard-Petersen CF, Sun S, Byrjalsen I, Christiansen C, Karsdal MA, Bay-Jensen AC (2018) Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis. Clin Exp Rheumatol 36(1):94–101

    PubMed  Google Scholar 

  100. Sluyter R, Shemon AN, Wiley JS (2004) Glu496 to Ala polymorphism in the P2X7 receptor impairs ATP-induced IL-1 beta release from human monocytes. J Immunol 172(6):3399–3405. https://doi.org/10.4049/jimmunol.172.6.3399

    Article  CAS  PubMed  Google Scholar 

  101. Spierings J, Van Eden W (2017) Heat shock proteins and their immunomodulatory role in inflammatory arthritis. Rheumatology 56(2):198–208. https://doi.org/10.1093/rheumatology/kew266

    Article  CAS  PubMed  Google Scholar 

  102. Srivastava P (2002) Roles of heat-shock proteins in innate and adaptive immunity. Nat Rev Immunol 2:185–194. https://doi.org/10.1038/nri749

    Article  CAS  PubMed  Google Scholar 

  103. Stocki P, Wang XN, Dickinson AM (2012) Inducible heat shock protein 70 reduces T cell responses and stimulatory capacity of monocyte-derived dendritic cells. J Biol Chem 287(15):12387–12394. https://doi.org/10.1074/jbc.M111.307579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Suwara MI, Green NJ, Borthwick LA, Mann J, Mayer-Barber KD, Barron L et al (2014) IL-1a released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts. Mucosal Immunol 7(3):684–693. https://doi.org/10.1038/mi.2013.87

    Article  CAS  PubMed  Google Scholar 

  105. Taha EA, Ono K, Eguchi T (2019) Roles of extracellular HSP as biomarkers in immune surveillance and immune evasion. Int J Mol Sci 20(18). https://doi.org/10.3390/ijms20184588

  106. Taha EA, Sogawa C, Okusha Y, Kawai H, Oo MW, Elseoudi A et al (2020) Knockout of MMP3 weakens solid tumor organoids and cancer extracellular vesicles. Cancer 12(5):1260, 1–29. https://doi.org/10.3390/cancers12051260

    Article  CAS  Google Scholar 

  107. Tesar BM, Jiang D, Liang J, Palmer SM, Noble PW, Goldstein DR (2006) The role of hyaluronan degradation products as innate alloimmune agonists. Am J Transplant Off J Am Soc Transplant Am Soc Transplant Surg 6(11):2622–2635. https://doi.org/10.1111/j.1600-6143.2006.01537.x

    Article  CAS  Google Scholar 

  108. Tovar-Camargo OA, Toden S, Goel A (2016) Exosomal microRNA biomarkers: emerging Frontiers in colorectal and other human cancers. Expert Rev Mol Diagn 16:553–567. https://doi.org/10.1586/14737159.2016.1156535

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Tracy EC, Bowman MJ, Henderson BW, Baumann H (2012) Interleukin-1α is the major alarmin of lung epithelial cells released during photodynamic therapy to induce inflammatory mediators in fibroblasts. Br J Cancer 107(9):1534–1546. https://doi.org/10.1038/bjc.2012.429

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Turnquist HR, Zhao Z, Rosborough BR, Liu Q, Castellaneta A, Isse K et al (2011) IL-33 expands suppressive CD11b+ Gr-1(int) and regulatory T cells, including ST2L+ Foxp3+ cells, and mediates regulatory T cell-dependent promotion of cardiac allograft survival. J Immunol 187(9):4598–4610. https://doi.org/10.4049/jimmunol.1100519

    Article  CAS  PubMed  Google Scholar 

  111. Uemura Y, Hayashi H, Takahashi T, Saitho T, Umeda R, Ichise Y et al (2015) [MMP-3 as a biomarker of disease activity of rheumatoid arthritis]. Rinsho Byori. Jpn J Clin Pathol 63(12):1357–1364. http://www.ncbi.nlm.nih.gov/pubmed/27089651

    CAS  Google Scholar 

  112. Van Eden W, Van Der Zee R, Prakken B (2005) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5:318–330. https://doi.org/10.1038/nri1593

    Article  CAS  PubMed  Google Scholar 

  113. Van Eden W, Van Herwijnen M, Wagenaar J, Van Kooten P, Broere F, Van Der Zee R (2013) Stress proteins are used by the immune system for cognate interactions with anti-inflammatory regulatory T cells. FEBS Lett 587:1951–1958. https://doi.org/10.1016/j.febslet.2013.05.024

    Article  CAS  PubMed  Google Scholar 

  114. Wallin RPA, Lundqvist A, Moré SH, Von Bonin A, Kiessling R, Ljunggren HG (2002) Heat-shock proteins as activators of the innate immune system. Trends Immunol 23:130–135. https://doi.org/10.1016/S1471-4906(01)02168-8

    Article  CAS  PubMed  Google Scholar 

  115. Wang XB, Bozdagi O, Nikitczuk JS, Zu WZ, Zhou Q, Huntley GW (2008) Extracellular proteolysis by matrix metalloproteinase-9 drives dendritic spine enlargement and long-term potentiation coordinately. Proc Natl Acad Sci U S A 105(49):19520–19525. https://doi.org/10.1073/pnas.0807248105

    Article  PubMed  PubMed Central  Google Scholar 

  116. Wieten L, Broere F, van der Zee R, Koerkamp EK, Wagenaar J, van Eden W (2007) Cell stress induced HSP are targets of regulatory T cells: a role for HSP inducing compounds as anti-inflammatory immuno-modulators? FEBS Lett 581:3716–3722. https://doi.org/10.1016/j.febslet.2007.04.082

    Article  CAS  PubMed  Google Scholar 

  117. Wolf R, Howard OMZ, Dong H-F, Voscopoulos C, Boeshans K, Winston J et al (2008) Chemotactic activity of S100A7 (Psoriasin) is mediated by the receptor for advanced glycation end products and potentiates inflammation with highly homologous but functionally distinct S100A15. J Immunol 181(2):1499–1506. https://doi.org/10.4049/jimmunol.181.2.1499

    Article  CAS  PubMed  Google Scholar 

  118. Wu J, Liu T, Rios Z, Mei Q, Lin X, Cao S (2017) Heat shock proteins and cancer. Trends Pharmacol Sci 38(3):226–256. https://doi.org/10.1016/j.tips.2016.11.009

    Article  CAS  PubMed  Google Scholar 

  119. Yang D, Chen Q, Yang H, Tracey KJ, Bustin M, Oppenheim JJ (2007) High mobility group box-1 protein induces the migration and activation of human dendritic cells and acts as an alarmin. J Leukoc Biol 81(1):59–66. https://doi.org/10.1189/jlb.0306180

    Article  CAS  PubMed  Google Scholar 

  120. Yang Y, Candelario-Jalil E, Thompson JF, Cuadrado E, Estrada EY, Rosell A et al (2010) Increased intranuclear matrix metalloproteinase activity in neurons interferes with oxidative DNA repair in focal cerebral ischemia. J Neurochem 112(1):134–149. https://doi.org/10.1111/j.1471-4159.2009.06433.x

    Article  CAS  PubMed  Google Scholar 

  121. Yebdri FB, Kukulski F, Tremblay A, Sévigny J (2009) Concomitant activation of P2Y2 and P2Y6 receptors on monocytes is required for TLR1/2-induced neutrophil migration by regulating IL-8 secretion. Eur J Immunol 39(10):2885–2894. https://doi.org/10.1002/eji.200939347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Yokota S i, Minota S, Fujii N (2006) Anti-HSP auto-antibodies enhance HSP-induced pro-inflammatory cytokine production in human monocytic cells via toll-like receptors. Int Immunol 18(4):573–580. https://doi.org/10.1093/intimm/dxh399

    Article  CAS  PubMed  Google Scholar 

  123. Zininga T, Ramatsui L, Shonhai A (2018) Heat shock proteins as immunomodulants. Molecules 23(11):2846. https://doi.org/10.3390/molecules23112846

    Article  CAS  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank Chiharu Sogawa, Yuka Okusha, Yanyin Lu, Manh Tien Tran, Keisuke Nakano, and Hotaka Kawai for illuminating discussion and experimentation. The authors appreciate Masaharu Takigawa, Stuart K. Calderwood, Kuniaki Okamoto, Ken-ichi Kozaki, and Ayano Satoh for mentorship and support. T.E. was supported by JSPS KAKENHI, grant numbers, JP17K11642-TE), JP17K11669-KOh, JP18K09789-KN, 19H04051-HO, 19H03817-MT, and by Suzuki Kenzo Memorial Foundation. E.A.T. was supported by the Egypt-Japan Education Partnership (EJEP) grant.

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  1. Authors Takanori Eguchi and Eman Ahmed Taha have equally contributed to this chapter.

Authors and Affiliations

  1. Department of Dental Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan

    Takanori Eguchi & Eman Ahmed Taha

  2. Department of Medical Bioengineering, Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan

    Eman Ahmed Taha

  3. Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt

    Eman Ahmed Taha

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  1. Takanori Eguchi
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Correspondence to Takanori Eguchi .

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  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, OH, USA

    Alexzander A. A. Asea

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

    Punit Kaur

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Eguchi, T., Taha, E.A. (2020). Extracellular Vesicle-Associated Moonlighting Proteins: Heat Shock Proteins and Metalloproteinases. In: Asea, A.A.A., Kaur, P. (eds) Heat Shock Proteins in Inflammatory Diseases. Heat Shock Proteins, vol 22. Springer, Cham. https://doi.org/10.1007/7515_2020_25

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