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Exercise-Induced Chaperokine Activity of Hsp70: Possible Role in Chronic Diseases

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Chaperokine Activity of Heat Shock Proteins

Part of the book series: Heat Shock Proteins ((HESP,volume 16))

Abstract

In recent years, strong effects of exercise on the immune system have been demonstrated in many studies. Indeed, beneficial effects of regular exercise on immune responses in diseases such as cancer, cardiovascular disease, neuromuscular disorders and diabetes have been observed. Growing evidence indicates that the stress-inducible form of Hsp70 (Hsp70; 72 kDa) is found in the extracellular milieu and can exert chaperoning and regulatory effects on various immunocompetent cells. In this regard, extracellular Hsp72 can stimulate immune responses such as macrophages, T lymphocytes and NK cells. We propose that extracellular Hsp72 is released following acute exercise and acts to stimulate the immune system. The chaperokine activity of eHsp72 would constitute one mechanism for cross talk between tissues after exercise and the adaptation to physical exercise. Here, we discuss the immunostimulatory and immunosuppressive activities of eHsp72 as a possible mechanism for the protective effects of regular physical exercise in chronic disease.

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Abbreviations

APC:

Antigen-presenting cells

CD:

Cluster of differentiation

CTLs:

Cytotoxic T lymphocytes

DC:

Dendritic cell

HSP:

Heat shock protein family

Hsp:

Heat shock proteins

IL-12:

Interleukin-12

IL-1β:

Interleukin-1β

IL-6:

Interleukin-6

LOX-1:

Lectin-like oxidized low-density lipoprotein (LDL) receptor-1

NEFA:

Non-esterified fatty acids

NF-kβ:

Nuclear factor kappa β

NK:

Natural killer

SR-A:

Macrophage scavenger receptor type A

Th1:

T helper 1

TLR:

Toll like receptors

TNF-α:

Tumor necrosis factor-alpha

References

  • Adachi H, Katsuno M, Waza M, Minamiyama M, Tanaka F, Sobue G (2009) Heat shock proteins in neurodegenerative diseases: pathogenic roles and therapeutic implications. Int J Hyperth 25:647–654

    Article  CAS  Google Scholar 

  • Apostolopoulos V, Borkoles E, Polman R, Stojanovska L (2014) Physical and immunological aspects of exercise in chronic diseases. Immunotherapy 6(10):1145–1157

    Article  CAS  PubMed  Google Scholar 

  • Arisi MF, Chirico EN, Sebeny R, Muthukumaran G, Mu A, De Jonghe BC, Margulies KB, Libonati JR (2017) Myocardial apoptosis and mesenchymal stem cells with acute exercise. Physiol Rep 5(11):e13297

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Asea A (2003) Chaperokine-induced signal transduction pathways. Exerc Immunol Rev 9:25–33

    PubMed  PubMed Central  Google Scholar 

  • Asea A (2005) Stress proteins and initiation of immune response: chaperokine activity of Hsp72. Exerc Immunol Rev 11:34–45

    PubMed  PubMed Central  Google Scholar 

  • Asea A (2006) Initiation of the immune response by extracellular Hsp72: chaperokine activity of Hsp72. Curr Immunol Rev 2:209–215

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Asea A, Kraeft SK, Kurt-Jones EA, Stevenson MA, Chen LB, Finberg RW, Koo GC, Calderwood SK (2000) HSP70 stimulates cytokine production through a CD14-dependant pathway, demonstrating its dual role as a chaperone and cytokine. Nat Med 6:435–442

    Article  CAS  PubMed  Google Scholar 

  • Asea A, Rehli M, Kabingu E, Boch JA, Bare O, Auron PE, Stevenson MA, Calderwood SK (2002) Novel signal transduction pathway utilized by extracellular HSP70: role of toll-like receptor (TLR)2 and TLR4. J Biol Chem 277:15028–15034

    Article  CAS  PubMed  Google Scholar 

  • Beckmann RP, Lovett M, Welch WJ (1992) Examining the function and regulation of hsp 70 in cells subjected to metabolic stress. J Cell Biol 117(6):1137–1150

    Article  CAS  PubMed  Google Scholar 

  • Bishopric NH, Andreka P, Slepak T, Webster KA (2001) Molecular mechanisms of apoptosis in the cardiac myocyte. Curr Opin Pharmacol 1:141–150

    Article  CAS  PubMed  Google Scholar 

  • Bittencourt A, Porto RR (2017) eHSP70/iHSP70 and divergent functions on the challenge: effect of exercise and tissue specificity in response to stress. Clin Physiol Funct Imaging 37(2):99–105

    Article  CAS  PubMed  Google Scholar 

  • Booth FW, Roberts CK, Laye MJ (2012) Lack of exercise is a major cause of chronic diseases. Compr Physiol 2(2):1143–1211

    PubMed  PubMed Central  Google Scholar 

  • Brolinson PG, Elliott D (2007) Exercise and the immune system. Clin Sports Med 26(3):311–319

    Article  PubMed  Google Scholar 

  • Bruinsma IB, de Jager M, Carrano A, Versleijen AA, Veerhuis R, Boelens W, Rosemuller AJ, de Waal RM, Verbeek MM (2011) Small heat shock proteins induce a cerebral inflammatory reaction. J Neurosci 31:11992–12000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bualeong T, Kebir S, Hof D, Goelz L, Graewe M, Ehrentraut SF, Knuefermann P, Baumgarten G, Meyer R, Ehrentraut H (2016) Tlr2 deficiency does not limit the development of left ventricular hypertrophy in a model of transverse aortic constriction induced pressure overload. J Negat Results Biomed 25(15):9

    Article  Google Scholar 

  • Bukau B, Horwich AL (1998) The Hsp70 and Hsp60 chaperone machines. Cell 92:351–366

    Article  CAS  PubMed  Google Scholar 

  • 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(3):272–286

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Carnini A, Scott LO, Ahrendt E, Proft J, Winkfein RJ, Kim SW, Colicos MA, Braun JE (2012) Cell line specific modulation of extracellular abeta42 by Hsp40. PLoS One 7:e37755

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Caux C, Massacrier C, Vanbervliet B, Dubois B, Van Kooten C, Durand I, Banchereau J (1994) Activation of human dendritic cells through CD40 cross-linking. J Exp Med 180:1263–1272

    Article  CAS  PubMed  Google Scholar 

  • Chiang HL, Terlecky SR, Plant CP, Dice JF (1989) A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins. Science 246(4928):382–385

    Article  CAS  PubMed  Google Scholar 

  • Cho JY, Um HS, Kang EB, Cho IH, Kim CH, Cho JS, Hwang DY (2010) The combination of exercise training and alpha-lipoic acid treatment has therapeutic effects on the pathogenic phenotypes of Alzheimer’s disease in NSE/APPsw-transgenic mice. Int J Mol Med 25(3):337–346

    Article  CAS  PubMed  Google Scholar 

  • Civitarese AE, Hesselink MKC, Russell AP, Ravussin E, Schrauwen P (2005) Glucose ingestion during exercise blunts exercise-induced gene expression of skeletal muscle fat oxidative genes. Am J Phys 289:E1023–E1029

    CAS  Google Scholar 

  • Clayton A, Turkes A, Navabi H, Mason MD, Tabi Z (2005) Induction of heat shock proteins in B-cell exosomes. J Cell Sci 118:3631–3638

    Article  CAS  PubMed  Google Scholar 

  • Coggan AR (1991) Plasma glucose metabolism during exercise in humans. Sports Med 11(2):102–124

    Article  CAS  PubMed  Google Scholar 

  • 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. Cell Stress Chaperones 16:235–249

    Article  CAS  PubMed  Google Scholar 

  • De Maio A, Vazquez D (2013) Extracellular heat shock proteins: a new location, a new function. Shock 40(4):239–246

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • De Nardo DG, Coussens LM (2007) Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 9(4):212

    Article  CAS  Google Scholar 

  • Evans CG, Wisen S, Gestwicki JE (2006) Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro. J Biol Chem 281:33182–33191

    Article  CAS  PubMed  Google Scholar 

  • Febbraio MA, Koukoulas I (2000) HSP72 gene expression progressively increases in human skeletal muscle during prolonged, exhaustive exercise. J Appl Physiol (1985) 89(3):1055–1060

    Article  CAS  Google Scholar 

  • Febbraio MA, Ott P, Nielsen HB, Steensberg A, Keller C, Krustrup P, Secher NH, Pedersen BK (2002) Exercise induces hepatosplanchnic release of heat shock protein 72 in humans. J Physiol 544:957–962

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Febbraio MA, Mesa JL, Chung J, Steensberg A, Keller C, Nielsen HB, Krustrup P, Ott P, Secher NH, Pedersen BK (2004) Glucose ingestion attenuates the exercise-induced increase in circulating heat shock protein 72 and heat shock protein 60 in humans. Cell Stress Chaperones 9(4):390–396

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fleshner M, Johnson JD (2005) Endogenous extra-cellular heat shock protein 72: releasing signal(s) and function. Int J Hyperth 21:457–471

    Article  CAS  Google Scholar 

  • Furrer R, Eisele PS, Schmidt A, Beer M, Handschin C (2017) Paracrine cross-talk between skeletal muscle and macrophages in exercise by PGC-1α-controlled BNP. Sci Rep 7:40789

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gajewski TF, Schreiber H, Fu YX (2013) Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol 14:1014–1022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • García JJ, Martín-Cordero L, Hinchado MD, Bote ME, Ortega E (2013) Effects of habitual exercise on the eHsp72-induced release of inflammatory cytokines by macrophages from obese Zucker rats. Int J Sports Med 34:559–564

    PubMed  Google Scholar 

  • 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 65:5238–5247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Genth-Zotz S, Bolger AP, Kalra PR, Haehling S, Doehner W, Coats A, Volk HD, Anker SD (2004) Heat shock protein 70 in patients with chronic heart failure: relation to disease severity and survival. Int J Cardiol 96:397–401

    Article  PubMed  Google Scholar 

  • Giraldo E, Martin-Cordero L, García JJ, Gehrmann M, Multhoff G, Ortega E (2010) Exercise-induced extracellular 72 kDa heat shock protein (Hsp72) stimulates neutrophil phagocytic and fungicidal capacities via TLR-2. Eur J Appl Physiol 108:217–225

    Article  CAS  PubMed  Google Scholar 

  • Gleeson M (2006) Immune system adaptation in elite athletes. Curr Opin Clin Nutr Metab Care 9(6):659–665

    Article  PubMed  Google Scholar 

  • Gleeson M (2007) Immune function in sport and exercise. J Appl Physiol 103(2):693–699

    Article  CAS  PubMed  Google Scholar 

  • Gleeson M, Nieman DC, Pedersen BK (2004) Exercise, nutrition and immune function. J Sports Sci 22:115–125

    Article  PubMed  Google Scholar 

  • Gleeson M, Bishop NC, Stensel DJ, Lindley MR, Mastana SS, Nimmo MA (2011) The anti-inflammatory effects of exercise: mechanisms and implications for the prevention and treatment of disease. Nat Rev Immunol 11(9):607–615

    Article  CAS  PubMed  Google Scholar 

  • Gomez-Merino D, Drogou C, Guezennec CY, Burnat P, Bourrilhon C, Tomaszewski A, Milhau S, Chennaoui M (2006) Comparison of systemic cytokine responses after a long distance triathlon and a 100-km run: relationship to metabolic and inflammatory processes. Eur Cytokine Netw 17(2):117–124

    CAS  PubMed  Google Scholar 

  • Gross C, Hansch D, Gastpar R, Multhoff G (2003) Interaction of heat shock protein 70 peptide with NK cells involves the NK receptor CD94. Biol Chem 384:267–279

    Article  CAS  PubMed  Google Scholar 

  • Guttman R, Lewis S, Rinzel J (1980) Control of repetitive firing in squid axon membrane as a model for a neuroneoscillator. J Physiol 305:377–395

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hamilton KL, Staib JL, Phillips T, Hess A, Lennon SL, Powers SK (2003) Exercise, antioxidants, and HSP72: protection against myocardial ischemia/reperfusion. Free Radic Biol Med 34(7):800–809

    Article  CAS  PubMed  Google Scholar 

  • Handschin C, Spiegelman BM (2008) The role of exercise and PGC1α in inflammation and chronic disease. Nature 454(7203):463–469

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hashemi SM, Hassan ZM, Soudi S, Shahabi S (2008) The effect of vaccination with the lysate of heat-shocked tumor cells on nitric oxide production in BALB/c mice with fibrosarcoma tumor. Cell Biol Int 32(7):835–840

    Article  CAS  PubMed  Google Scholar 

  • Haworth R, Platt N, Keshav S, Hughes D, Darley E, Suzuki H, Kurihara Y, Kodama T, Gordon S (1997) The macrophage scavenger receptor type A is expressed by activated macrophages and protects the host against lethal endotoxic shock. J Exp Med 186:1431–1439

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heck TG, Scholer CM, Bittencourt PIH (2011) Hsp70 expression: does it a novel fatigue signalling factor from immune system to brain? Cell Biochem Funct 29:215–226

    Article  CAS  PubMed  Google Scholar 

  • Henstridge DC, Febbraio MA, Hargreaves M (2016) Heat shock proteins and exercise adaptations. Our knowledge thus far and the road still ahead. J Appl Physiol 120(6):683–691

    Article  CAS  PubMed  Google Scholar 

  • Hojman P (2017) Exercise protects from cancer through regulation of immune function and inflammation. Biochem Soc Trans 45(4):905–911

    Article  CAS  PubMed  Google Scholar 

  • Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK (2011) Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab 301(3):E504–E510

    Article  CAS  PubMed  Google Scholar 

  • Horn P, Kalz A, Lim CL, Pyne D, Saunders P, Mackinnon L, Peake J, Suzuki K (2007) Exercise-recruited NK cells display exercise-associated eHSP-70. Exerc Immunol Rev 13:100–111

    PubMed  Google Scholar 

  • Horowitz JF, Klein S (2000) Lipid metabolism during endurance exercise. Am J Clin Nutr 72(2 Suppl):558S–563S

    Article  CAS  PubMed  Google Scholar 

  • Johnson JD, Fleshner M (2006) Releasing signals, secretory pathways, and immune function of endogenous extracellular heat shock protein 72. J Leukoc Biol 79:425–434

    Article  CAS  PubMed  Google Scholar 

  • Johnson JD, Campisi J, Sharkey CM, Kennedy SL, Nickerson M, Fleshner M (2005) Adrenergic receptors mediate stress-induced elevations in extracellular Hsp72. J Appl Physiol 99:1789–1795

    Article  CAS  PubMed  Google Scholar 

  • Knight JA (2012) Physical inactivity: associated diseases and disorders. Ann Clin Lab Sci 42(3):320–337

    PubMed  Google Scholar 

  • Kovalchin JT, Wang R, Wagh MS, Azoulay J, Sanders M, Chandawarkar RY (2006) In vivo delivery of heat shock protein 70 accelerates wound healing by up-regulating macrophage-mediated phagocytosis. Wound Repair Regen 14(2):129–137

    Article  PubMed  Google Scholar 

  • Krause M, Rodrigues-Krause Jda C (2011) Extracellular heat shock proteins (eHSP70) in exercise: possible targets outside the immune system and their role for neurodegenerative disorders treatment. Med Hypotheses 76(2):286–290

    Article  CAS  PubMed  Google Scholar 

  • Kujala UM (2004) Evidence for exercise therapy in the treatment of chronic disease based on at least three randomized controlled trials – summary of published systematic reviews. Scand J Med Sci Sports 14(6):339–345

    Article  PubMed  Google Scholar 

  • Lancaster GI, Febbraio MA (2005) Mechanisms of stress-induced cellular HSP72 release: implications for exercise-induced increases in extracellular HSP72. Exerc Immunol Rev 11:46–52

    PubMed  Google Scholar 

  • Lancaster GI, Halson SL, Khan Q, Drysdale P, Jeukendrup AE, Drayson MT, Gleeson M (2004a) The effects of acute exhaustive exercise and intensified training on type 1/type 2 T cell distribution and cytokine production. Exerc Immunol Rev 10:91–106

    PubMed  Google Scholar 

  • Lancaster GI, Moller K, Nielsen B, Secher NH, Febbraio MA, Nybo L (2004b) Exercise induces the release of heat shock protein 72 from the human brain in vivo. Cell Stress Chaperones 9:276–280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lang CH, Silvis C, Deshpande N, Nystrom G, Frost RA (2003) Endotoxin stimulates in vivo expression of inflammatory cytokines tumor necrosis factor alpha, interleukin-1beta, –6, and high-mobility-group protein-1 in skeletal muscle. Shock 19:538–546

    Article  CAS  PubMed  Google Scholar 

  • LaVoy EC, Hussain M, Reed J, Kunz H, Pistillo M, Bigley AB, Simpson RJ (2017) T-cell redeployment and intracellular cytokine expression following exercise: effects of exercise intensity and cytomegalovirus infection. Physiol Rep 5(1):e13070

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee BJ, Clarke ND, Hankey J, Thake CD (2017) Whole body precooling attenuates the extracellular HSP72, IL-6 and IL-10 responses after an acute bout of running in the heat. J Sports Sci 5:1–8

    Article  Google Scholar 

  • Lehner T, Wang Y, Whittall T, McGowan E, Kelly CG, Singh M (2004) Functional domains of HSP70 stimulate generation of cytokines and chemokines, maturation of dendritic cells and adjuvanticity. Biochem Soc Trans 32:629–632

    Article  CAS  PubMed  Google Scholar 

  • Lin L, Knowlton AA (2014) Innate immunity and cardiomyocytes in ischemic heart disease. Life Sci 100(1):1–8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lin Y, Lee H, Berg AH, Lisanti MP, Shapiro L, Scherer PE (2000) The lipopolysaccharide-activated toll-like receptor (TLR)-4 induces synthesis of the closely related receptor TLR-2 in adipocytes. J Biol Chem 275(32):24255–24263

    Article  CAS  PubMed  Google Scholar 

  • Liu Z, Li X, Qiu L, Zhang X, Chen L, Cao S, Wang F, Meng S (2009) Treg suppress CTL responses upon immunization with HSP gp96. Eur J Immunol 39(11):3110–3120

    Article  CAS  PubMed  Google Scholar 

  • Locke M, Noble EG (1995) Stress proteins: the exercise response. Can J Appl Physiol 20(2):155–167

    Article  CAS  PubMed  Google Scholar 

  • Luo X, Tao L, Lin P, Mo X, Chen H (2012) Extracellular heat shock protein 72 protects schwann cells from hydrogen peroxide-induced apoptosis. J Neurosci Res 90:1261–1269

    Article  CAS  PubMed  Google Scholar 

  • Madden LA, Sandstrom ME, Lovell RJ, McNaughton L (2008) Inducible heat shock protein 70 and its role in preconditioning and exercise. Amino Acids 34:511–516

    Article  CAS  PubMed  Google Scholar 

  • Marshall HC, Ferguson RA, Nimmo MA (2006) Human resting extracellular heat shock protein 72 concentration decreases during the initial adaptation to exercise in a hot, humid environment. Cell Stress Chaperones 11:129–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mathur S, Walley KR, Wang Y, Indrambarya T, Boyd JH (2011) Extracellular heat shock protein 70 induces cardiomyocyte inflammation and contractile dysfunction via TLR2. Circ J 75(10):2445–2452

    Article  CAS  PubMed  Google Scholar 

  • Matzinger P, Fuchs EJ (1996) Beyond self and non-self: immunity is a conversation, not a war. J NIH Res 8:35–39

    Google Scholar 

  • Mehrholz J, Kugler J, Storch A, Pohl M, Elsner B, Hirsch K (2015) Treadmill training for patients with Parkinson’s disease. Cochrane Database Syst Rev 22(8):CD007830

    Google Scholar 

  • Mizzen LA, Welch WJ (1988) Characterization of the thermotolerant cell. I. Effects on protein synthesis activity and the regulation of heat-shock protein 70 expression. J Cell Biol 106:1105–1116

    Article  CAS  PubMed  Google Scholar 

  • Moehler MH, Zeidler M, Wilsberg V, Cornelis JJ, Woelfel T, Rommelaere J, Galle PR, Heike M (2005) Parvovirus H-1-induced tumor cell death enhances human immune response in vitro via increased phagocytosis, maturation, and cross-presentation by dendritic cells. Hum Gene Ther 16:996–1005

    Article  CAS  PubMed  Google Scholar 

  • Molanouri Shamsi M, Hassan ZH, Gharakhanlou R, Quinn LS, Azadmanesh K, Baghersad L, Isanejad A, Mahdavi M (2014) Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training. Endocrine 46(1):60–69

    Article  CAS  PubMed  Google Scholar 

  • Molanouri Shamsi M, Hassan ZM, Quinn LS, Gharakhanlou R, Baghersad L, Mahdavi M (2015) Time course of IL-15 expression after acute resistance exercise in trained rats: effect of diabetes and skeletal muscle phenotype. Endocrine 49(2):396–403

    Article  CAS  PubMed  Google Scholar 

  • Molanouri Shamsi M, Mahdavi M, Quinn LS, Gharakhanlou R, Isanegad A (2016) Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats. Cell Stress Chaperones 21(5):783–791

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Molanouri Shamsi M, Chekachak S, Soudi S, Quinn LS, Ranjbar K, Chenari J, Yazdi MH, Mahdavi M (2017a) Combined effect of aerobic interval training and selenium nanoparticles on expression of IL-15 and IL-10/TNF-α ratio in skeletal muscle of 4T1 breast cancer mice with cachexia. Cytokine 90:100–108

    Article  CAS  PubMed  Google Scholar 

  • Molanouri Shamsi M, Najedi S, Hassan ZM, Isanejad A, Mahdavi M (2017b) Short term exercise training enhances cell-mediated responses to HSV-1 vaccine in mice. Microb Pathog 110:457–463

    Article  CAS  PubMed  Google Scholar 

  • Monninkhof EM, Elias SG, Vlems FA, van der Tweel I, Schuit AJ, Voskuil DW, van Leeuwen FE (2007) Physical activity and breast cancer: a systematic review. Epidemiology 18:137–157

    Article  PubMed  Google Scholar 

  • Moseley P (2000) Stress proteins and the immune response. Immunopharmacology 48(3):299–302

    Article  CAS  PubMed  Google Scholar 

  • Motta A, Schmitz C, Rodrigues L, Ribeiro F, Teixeira C, Detanico T, Bonan C, Zwickey H, Bonorino C (2007) Mycobacterium tuberculosis heat-shock protein 70 impairs maturation of dendritic cells from bone marrow precursors, induces interleukin-10 production and inhibits T-cell proliferation in vitro. Immunology 121:462–472

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Multhoff G, Botzler C, Wiesnet M, Müller E, Meier T, Wilmanns W, Issels RD (1995) A stress-inducible 72-kDa heat-shock protein (HSP72) is expressed on the surface of human tumor cells, but not on normal cells. Int J Cancer 61(2):272–279

    Article  CAS  PubMed  Google Scholar 

  • Murase Y, Shimizu K, Tanimura Y, Hanaoka Y, Watanabe K, Kono I, Miyakawa S (2016) Salivary extracellular heat shock protein 70 (eHSP70) levels increase after 59 min of intense exercise and correlate with resting salivary secretory immunoglobulin A (SIgA) levels at rest. Cell Stress Chaperones 21(2):261–269

    Article  CAS  PubMed  Google Scholar 

  • Nakata N, Kato H, Kogure K (1993) Inhibition of ischaemic tolerance in the gerbil hippocampus by quercetin and anti-heat shock protein-70 antibody. Neuroreport 4:695–698

    Article  CAS  PubMed  Google Scholar 

  • Nieman DC (1994) Exercise, infection and immunity. Int J Sports Med 15:S131–S141

    Article  PubMed  Google Scholar 

  • Noble EG, Milne KJ, Melling CW (2008) Heat shock proteins and exercise: a primer. Appl Physiol Nutr Metab 33:1050–1065

    Article  CAS  PubMed  Google Scholar 

  • Nocon M, Hiemann T, Muller-Riemenschneider F, Thalau F, Roll S, Willich SN (2008) Association of physical activity with all-cause and cardiovascular mortality: a systematic review and meta-analysis. Eur J Cardiovasc Prev Rehabil 15:239–246

    Article  PubMed  Google Scholar 

  • Ogura Y, Naito H, Akin S, Ichinoseki-Sekine N, Kurosaka M, Kakigi R, Sugiura T, Powers SK, Katamoto S, Demirel HA (2008) Elevation of body temperature is an essential factor for exercise-increased extracellular heat shock protein 72 level in rat plasma. Am J Physiol Regul Integr Comp Physiol 294(5):R1600–R1607

    Article  CAS  PubMed  Google Scholar 

  • Ortega E (2016) The “bioregulatory effect of exercise” on the innate/inflammatory responses. J Physiol Biochem 72(2):361–369

    Article  CAS  PubMed  Google Scholar 

  • Ortega E, Giraldo E, Hinchado MD, Martínez M, Ibáñez S, Cidoncha A, Collazos ME, García JJ (2006) Role of Hsp72 and norepinephrine in the moderate exercise-induced stimulation of neutrophils’ microbicide capacity. Eur J Appl Physiol 98(3):250–255

    Article  CAS  PubMed  Google Scholar 

  • Panjwani NN, Popova L, Srivastava PK (2002) Heat shock proteins gp96 and hsp70 activate the release of nitric oxide by APCs. J Immunol 168(6):2997–3003

    Article  CAS  PubMed  Google Scholar 

  • Park SW, Goodpaster BH, Lee JS, Kuller LH, Boudreau R, de Rekeneire N, Harris TB, Kritchevsky S, Tylavsky FA, Nevitt M, Cho YW, Newman AB, Health, Aging, and Body Composition Study (2009) Excessive loss of skeletal muscle mass in older adults with type 2 diabetes. Diabetes Care 32(11):1993–1997

    Article  PubMed  PubMed Central  Google Scholar 

  • Peake JM, Neubauer O, Walsh NP, Simpson RJ (2017) Recovery of the immune system after exercise. J Appl Physiol 122(5):1077–1087

    Article  CAS  PubMed  Google Scholar 

  • Peart DJ, McNaughton LR, Midgley AW, Taylor L, Towlson C, Madden LA, Vince RV (2011) Pre-exercise alkalosis attenuates the heat shock protein 72 response to a single-bout of anaerobic exercise. J Sci Med Sport 14(5):435–440

    Article  PubMed  Google Scholar 

  • Pedersen BK (2011) Exercise-induced myokines and their role in chronic diseases. Brain Behav Immun 25(5):811–816

    Article  CAS  PubMed  Google Scholar 

  • Pedersen BK, Bruunsgaard H (1995) How physical exercise influences the establishment of infections. Sports 19:393–400

    CAS  Google Scholar 

  • Pedersen BK, Steensberg A, Fischer C, Keller C, Ostrowski K, Schjerling P (2001) Exercise and cytokines with particular focus on musclederived IL-6. Exerc Immunol Rev 7:18–31

    CAS  PubMed  Google Scholar 

  • Périard JD, Ruell P, Caillaud C, Thompson MW (2012) Plasma Hsp72 (HSPA1A) and Hsp27 (HSPB1) expression under heat stress: influence of exercise intensity. Cell Stress Chaperones 17(3):375–383

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Peters EM, Goetzsche JM, Grobbelaar B, Noakes TD (1993) Vitamin C supplementation reduces the incidence of post-race symptoms of upper respiratory tract infection in ultramarathonrunners. Am J Clin Nutr 57:170–174

    Article  CAS  PubMed  Google Scholar 

  • Pilegaard H, Keller C, Steensberg A, Helge JW, Pedersen BK, Saltin B, Neufer PD (2002) Influence of pre-exercise muscle glycogen content on exercise-induced transcriptional regulation of metabolic genes. J Physiol 541:261–271

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pillon NJ, Bilan PJ, Fink LN, Klip A (2013) Cross-talk between skeletal muscle and immune cells: muscle-derived mediators and metabolic implications. Am J Physiol Endocrinol Metab 304(5):E453–E465

    Article  CAS  PubMed  Google Scholar 

  • Radford NB, Fina M, Benjamin IJ, Moreadith RW, Graves KH, Zhao P, Gavva S, Wiethoff A, Sherry AD, Malloy CR, Williams RS (1996) Cardioprotective effects of 70-kDa heat shock protein in transgenic mice. Proc Natl Acad Sci 93:2339–2342

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rodrigues-Krause J, Krause M, O’Hagan C, De Vito G, Boreham C, Murphy C, Newsholme P, Colleran G (2012) Divergence of intracellular and extracellular HSP72 in type 2 diabetes: does fat matter? Cell Stress Chaperones 17(3):293–302

    Article  PubMed  PubMed Central  Google Scholar 

  • Ronsen O, Pedersen BK, Oritsland TR, Bahr R, Kjeldsen-Kragh J (2001) Leukocyte counts and lymphocyte responsiveness associated with repeated bouts of strenuous endurance exercise. J Appl Physiol 91:425–434

    Article  CAS  PubMed  Google Scholar 

  • Rubio E, Valenciano AI, Segundo C, Sanchez N, de Pablo F, de la Rosa EJ (2002) Programmed cell death in the neurulating embryo is prevented by the chaperone heat shock cognate 70. Eur J Neurosci 15:1646–1654

    Article  PubMed  Google Scholar 

  • Ruell PA, Thompson MW, Hoffman KM, Brotherhood JR, Richards DA (2006) Plasma Hsp72 is higher in runners with more serious symptoms of exertional heat illness. Eur J Appl Physiol 97:732–736

    Article  CAS  PubMed  Google Scholar 

  • Salo DC, Donovan CM, Davies KJ (1991) HSP70 and other possible heat shock or oxidative stress proteins are induced in skeletal muscle, heart, and liver during exercise. Free Radic Biol Med 11(3):239–246

    Article  CAS  PubMed  Google Scholar 

  • Scharhag J, George K, Shave R, Urhausen A, Kindermann W (2008) Exercise-associated increases in cardiac biomarkers. Med Sci Sports Exerc 40(8):1408–1415

    Article  PubMed  Google Scholar 

  • Shave R, Baggish A, George K, Wood M, Scharhag J, Whyte G, Gaze D, Thompson PD (2010) Exercise-induced cardiac troponin elevation: evidence, mechanisms, and implications. J Am Coll Cardiol 56(3):169–176

    Article  CAS  PubMed  Google Scholar 

  • Smolka MB, Zoppi CC, Alves AA, Silveira LR, Marangoni S, Pereira-Da-Silva L, Novello JC, Macedo DV (2000) HSP72 as a complementary protection against oxidative stress induced by exercise in the soleus muscle of rats. Am J Physiol Regul Integr Comp Physiol 279(5):R1539–R1545

    Article  CAS  PubMed  Google Scholar 

  • Sondermann H, Becker T, Mayhew M, Wieland F, Hartl FU (2000) Characterization of a receptor for heat shock protein 70 on macrophages and monocytes. Biol Chem 381(12):1165–1174

    Article  CAS  PubMed  Google Scholar 

  • Starkie R, Ostrowski SR, Jauffred S, Febbraio M, Pedersen BK (2003) Exercise and IL-6 infusion inhibit endotoxin-induced TNF-alpha production in humans. FASEB J 17(8):884–886

    Article  CAS  PubMed  Google Scholar 

  • Suzuki K, Peake J, Nosaka K, Okutsu M, Abbiss CR, Surriano R, Bishop D, Quod MJ, Lee H, Martin DT, Laursen PB (2006) Changes in markers of muscle damage, inflammation and HSP70 after an Ironman triathlon race. Eur J Appl Physiol 98:525–534

    Article  CAS  PubMed  Google Scholar 

  • Theriault JR, Adachi H, Calderwood SK (2006) Role of scavenger receptors in the binding and internalization of heat shock protein 70. J Immunol 177:8604–8611

    Article  CAS  PubMed  Google Scholar 

  • 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(Pt 4):636–639

    Article  CAS  PubMed  Google Scholar 

  • Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalainen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, Uusitupa M (2001) Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344:1343–1350

    Article  CAS  PubMed  Google Scholar 

  • Udono H, Srivastava PK (1993) Heat shock protein 70-associated peptides elicit specific cancer immunity. J Exp Med 178:1391–1396

    Article  CAS  PubMed  Google Scholar 

  • van Eden W, van der Zee R, Prakken B (2005) Heat-shock proteins induce T-cell regulation of chronic inflammation. Nat Rev Immunol 5(4):318–330

    Article  PubMed  CAS  Google Scholar 

  • van Hall G (2015) The physiological regulation of skeletal muscle fatty acid supply and oxidation during moderate-intensity exercise. Sports Med 1:S23–S32

    Article  Google Scholar 

  • 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 180:4299–4307

    Article  CAS  PubMed  Google Scholar 

  • Walsh RC, Koukoulas I, Garnham A, Moseley PL, Hargreaves M, Febbraio MA (2001) Exercise increases serum Hsp72 in humans. Cell Stress Chaperones 6:386–393

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Walters TJ, Ryan KL, Tehrany MR, Jones MB, Paulus LA, Mason PA (1998) HSP70 expression in the CNS in response to exercise and heat stress in rats. J Appl Physiol 84(4):1269–1277

    Article  CAS  PubMed  Google Scholar 

  • Wang Y, Whittall T, McGowan E, Younson J, Kelly C, Bergmeier LA, Singh M, Lehner T (2005) Identification of stimulating and inhibitory epitopes within the heat shock protein 70 molecule that modulate cytokine production and maturation of dendritic cells. J Immunol 174:3306–3316

    Article  CAS  PubMed  Google Scholar 

  • Welc SS, Clanton TL (2013) The regulation of interleukin-6 implicates skeletal muscle as an integrative stress sensor and endocrine organ. Exp Physiol 98(2):359–371

    Article  CAS  PubMed  Google Scholar 

  • Weng D, Song B, Koido S, Calderwood SK, Gong J (2013) Immunotherapy of radioresistant mammary tumors with early metastasis using molecular chaperone vaccines combined with ionizing radiation. J Immunol 191:755–763

    Article  CAS  PubMed  Google Scholar 

  • Whitham M, Fortes MB (2008) Heat shock protein 72: release and biological significance during exercise. Front Biosci 13:1328–1339

    Article  CAS  PubMed  Google Scholar 

  • Yu X, Guo C, Yi H, Qian J, Fisher PB, Subjeck JR, Wang XY (2013) A multifunctional chimeric chaperone serves as a novel immune modulator inducing therapeutic antitumor immunity. Cancer Res 73(7):2093–2103

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhen L, He M, Long M, Blomgran R, Stendahl O (2004) Pathogen-induced apoptotic neutrophils express heat shock proteins and elicit activation of human macrophages. J Immunol 173:6319–6326

    Article  Google Scholar 

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Acknowledgments

This work was supported by the Research Center of Tarbiat Modarres University (TMU), Tehran, Iran. We wish to thank Professor Yaghob Fathoallahy for his kind help and sincere cooperation.

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Authors and Affiliations

  1. Department of Physical Education & Sport Sciences, Faculty of Humanities, Tarbiat Modares University, Tehran, Iran

    Mahdieh Molanouri Shamsi & Reza Gharakhanlou

  2. Department of Immunology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran

    Zuhair Mohammad Hassan

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  1. Mahdieh Molanouri Shamsi
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  2. Zuhair Mohammad Hassan
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  3. Reza Gharakhanlou
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Correspondence to Mahdieh Molanouri Shamsi .

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Editors and Affiliations

  1. Department of Medicine and Director, 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 Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, TX, USA

    Punit Kaur

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Molanouri Shamsi, M., Hassan, Z.M., Gharakhanlou, R. (2019). Exercise-Induced Chaperokine Activity of Hsp70: Possible Role in Chronic Diseases. In: Asea, A., Kaur, P. (eds) Chaperokine Activity of Heat Shock Proteins . Heat Shock Proteins, vol 16. Springer, Cham. https://doi.org/10.1007/978-3-030-02254-9_10

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