Abstract
Heat shock proteins (Hsp) form a large family of proteins that are ubiquitously present in all organisms. In the absence of destabilising stimuli, Hsp are expressed at low levels, but their expression can be highly induced by various noxious conditions such as heat, oxygen stress and infection. Hsp have been reported to interfere with inflammatory processes and their induction is well known to decrease with aging. In the present study we have investigated Hsp70 serum concentrations using an optimised ELISA in elderly patients, recruited from a geriatric University Hospital ward. Our resultsportray positive correlations between the serum levels of Hsp 70 and various markers of inflammation (monocyte count, serum concentration of TNF-α, plasma concentrations of C-reactive protein, and fibrinogen), explaining the difference in Hsp70 serum concentrations in these subjects with various degrees of inflammation. We conclude that Hsp 70 is involved in inflammatory diseases and that the serum level of Hsp 70 is directly linked to the inflammatory status of the subject. However, the nature of this relationship remains to be elucidated.
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Barrios C, Tougne C, Polla BS, Lambert PH and Del Giudice G (1994) Specificity of antibodies induced after immunization of mice with the mycobacterial heat shock protein of 65 kD. Clin Exp Immunol 98: 224-228
Blake MJ, Fargnoli J, Gershon D and Holbrook NJ (1991a) Concomitant decline in heat-induced hyperthermia and HSP70 mRNA expression in aged rats. Am J Physiol 260: 663-667
Blake MJ, Udelsman R, Feulner GJ, Norton DD and Holbrook NJ (1991b) Stress-induced heat shock protein 70 expression in adrenal cortex: an adrenocorticotropic hormone-sensitive, agedependent response. Proc Natl Acad Sci USA 88: 9873-9877
Bonelli MA, Alfieri RR, Petronini PG, Brigotti M, Campanini C and Borghetti AF (1999) Attenuated expression of 70-kDa heat shock protein in WI-38 human fibroblasts during aging in vitro. Exp Cell Res 252: 20-32
Buchman TG, Cabin DE, Vickers S, Deutschman CS, Delgado E, Sussman MM and Bulkley GB (1990) Molecular biology of circulatory shock. Part II. Expression of four groups of hepatic genes is enhanced after resuscitation from cardiogenic shock. Surgery 108: 559-566
Chen HC, Guh JY, Tsai JH and Lai YH (1999) Induction of heat shock protein 70 protects mesangial cells against oxidative injury. Kidney Int 56: 1270-1273
Collins PL and Hightower LE (1982) Newcastle disease virus stimulates the cellular accumulation of stress (heat shock) mRNAs and proteins. J Virol 44: 703-707
Craig EA and Gross CA (1991) Is hsp70 the cellular thermometer? Trends Biochem Sci 16: 135-140
Currie RW (1987) Effects of ischemia and perfusion temperature on the synthesis of stress-induced (heat shock) proteins in isolated and perfused rat hearts. J Mol Cell Cardiol 19: 795-808
Deguchi Y and Kishimoto S (1990) Enhanced expression of the heat shock protein gene in peripheral blood mononuclear cells of patients with active systemic lupus erythematosus. Ann Rheum Dis 49: 893-895
Deguchi Y, Negoro S and Kishimoto S (1987) Heat-shock protein synthesis by human peripheral mononuclear cells from SLE patients. Biochem Biophys Res Commun 148: 1063-1068
Delogu G, Lo Bosco L, Marandola M, Famularo G, Lenti L, Ippoliti F and Signore L (1997) Heat shock protein (HSP70) expression in septic patients. J Crit Care 12: 188-192
Di Cesare S, Poccia F, Mastino A and Colizzi V (1992) Surface expressed heat-shock proteins by stressed or human immunodeficiency virus (HIV)-infected lymphoid cells represent the target for antibody-dependent cellular cytotoxicity. Immunology 76: 341-343
Effros RB, Zhu X and Walford RL (1994) Stress response of senescent T lymphocytes: reduced hsp70 is independent of the proliferative block. J Gerontol 49: 65-70
Emami A, Schwartz JH and Borkan SC (1991) Transient ischemia or heat stress induces a cytoprotectant protein in rat kidney. Am J Physiol 260: 479-485
Faassen AE, O'Leary JJ, Rodysill KJ, Bergh N and Hallgren HM (1989) Diminished heat-shock protein synthesis following mitogen stimulation of lymphocytes from aged donors. Exp Cell Res 183: 326-334
Fargnoli J, Kunisada T, Fornace AJ Jr, Schneider EL and Holbrook NJ (1990) Decreased expression of heat shock protein 70 mRNA and protein after heat treatment in cells of aged rats. Proc Natl Acad Sci USA 87: 846-850
Fincato G, Polentarutti N, Sica A, Mantovani A and Colotta F (1991) Expression of a heat-inducible gene of the HSP70 family in human myelomonocytic cells: regulation by bacterial products and cytokines. Blood 77: 579-586
Forsdyke DR (1985) Heat shock proteins defend against intracellular pathogens: a non-immunological basis for self/non-self discrimination? J Theor Biol 115: 471-473
Gabay C and Kushner I (1999) Acute-phase proteins and other systemic responses to inflammation. N Engl JMed 340: 448-454
Gingalewski C, Theodorakis NG, Yang J, Beck SC and De Maio A (1996) Distinct expression of heat shock and acute phase genes during regional hepatic ischemia-reperfusion. Am J Physiol 271: 634-640
Harrison PJ, Procter AW, Exworthy T, Roberts GW, Najlerahim A, Barton AJ and Pearson RC (1993) Heat shock protein (hsx70) mRNA expression in human brain: effects of neurodegenerative disease and agonal state. Neuropathol Appl Neurobiol 19: 10-21
Heydari AR, Wu B, Takahashi R, Strong R and Richardson A (1993) Expression of heat shock protein 70 is altered by age and diet at the level of transcription. Mol Cell Biol 13: 2909-2918
Heydari AR, Takahashi R, Gutsmann A, You S and Richardson A (1994) Hsp70 and aging. Experientia 50: 1092-1908
Jurivich DA, Pachetti C, Qiu L and Welk JF (1995) Salicylate triggers heat shock factor differently than heat. J Biol Chem 270: 24489-24495
Kantengwa S and Polla BS (1993) Phagocytosis of Staphylococcus aureus induces a selective stress response in human monocytesmacrophages (M phi): modulation by M phi differentiation and by iron. Infect Immun 61: 1281-1287
Kiang JG and Tsokos GC (1998) Heat shock protein 70 kDa: molecular biology, biochemistry, and physiology. Pharmacol Ther 80: 183-201
Kilgore JL, Musch TI and Ross CR (1998) Physical activity, muscle, and the HSP70 response. Can J Appl Physiol 23: 245-260
Knowlton AA, Brecher P and Apstein CS (1991) Rapid expression of heat shock protein in the rabbit after brief cardiac ischemia. J Clin Invest 87: 139-147
Kume M, Yamamoto Y, Saad S, Gomi T, Kimoto S, Shimabukuro T, Yagi T, Nakagami M, Takada Y, Morimoto T and Yamaoka Y (1996) Ischemic preconditioning of the liver in rats: implications of heat shock protein induction to increase tolerance of ischemiareperfusion injury. J Lab Clin Med 128: 251-258
La Thangue NB and Latchman DS (1988) A cellular protein related to heat-shock protein 90 accumulates during herpes simplex virus infection and is overexpressed in transformed cells. Exp Cell Res 178: 169-179
Lamb JR, Bal V, Rothbard JB, Mehlert A, Mendez-Samperio P and Young DB (1989) The mycobacterial GroEL stress protein: a common target of T-cell recognition in infection and autoimmunity. J Autoimmun 2(Suppl): 93-100
Lee BS, Chen J, Angelidis C, Jurivich DA and Morimoto RI (1995) Pharmacological modulation of heat shock factor 1 by antiinflammatory drugs results in protection against stress-induced cellular damage. Proc Natl Acad Sci USA 92: 7207-7211
Li Z (1997) Priming of T cells by heat shock protein-peptide complexes as the basis of tumor vaccines. Semin Immunol 9: 315-322
Lindquist S and Craig EA (1988) The heat-shock proteins. Annu Rev Genet 22: 631-677
Locke M and Tanguay RM (1996) Diminished heat shock response in the aged myocardium. Cell Stress Chaperones 1: 251-260
Mayer MP and Bukau B (1998) Hsp70 chaperone systems: diversity of cellular functions and mechanism of action. Biol Chem 379: 261-268
Mehta HB, Popovich BK and Dillmann WH (1988) Ischemia induces changes in the level of mRNAs coding for stress protein 71 and creatine kinase M. Circ Res 63: 512-517
Mistry Y, Young DB and Mukherjee R (1992) hsp70 synthesis in Schwann cells in response to heat shock and infection with Mycobacterium leprae. Infect Immun 60: 3105-3110
Moore SA, Lopez A, Richardson A and Pahlavani MA (1998) Effect of age and dietary restriction on expression of heat shock protein 70 in rat alveolar macrophages. Mech Ageing Dev 104: 59-73
Moseley PL (1998) Heat shock proteins and the inflammatory response. Ann N Y Acad Sci 856: 206-213
Munoz MG, Jeremias J and Witkin SS (1996) The 60 kDa heat shock protein in human semen: relationship with antibodies to spermatozoa and Chlamydia trachomatis. Hum Reprod 11: 2600-2603
Nakano M, Knowlton AA, Yokoyama T, Lesslauer W and Mann DL (1996) Tumor necrosis factor-alpha-induced expression of heat shock protein 72 in adult feline cardiac myocytes. Am J Physiol 270: 1231-239
Niedzwiecki A, Kongpachith AM and Fleming JE (1991) Aging affects expression of 70-kDa heat shock proteins in Drosophila. J Biol Chem 266: 9332-9338
Njemini R, Vanden Abeele M, Demanet C, Lambert M, Vandebosch S and Mets T (2002) Age-related decrease in the inducibility of heat-shock protein 70 in human peripheral blood mononuclear cells. J Clin Immunol 22: 195-205
Njemini R, Lambert M, Demanet C, Vanden Abeele M, Vandebosch S and Mets T (2003a) The induction of heat shock protein 70 in peripheral mononuclear blood cells in elderly patients: a role for inflammatory markers. Human Immunol 64: 575-585
Njemini R, Lambert M, Demanet C and Mets T (2003b) Elevated serum heat-shock protein 70 levels in patients with acute infection: use of an optimized enzyme-linked immunosorbent assay. Scand J Immunol 58: 664-669
Nowak TS Jr, Bond U and Schlesinger MJ (1990) Heat shock RNA levels in brain and other tissues after hyperthermia and transient ischemia. J Neurochem 54: 451-458
Pahlavani MA, Harris MD, Moore SA, Weindruch R and Richardson A (1995) The expression of heat shock protein 70 decreases with age in lymphocytes from rats and rhesus monkeys. Exp Cell Res 218: 310-318
Phillips B, Abravaya K and Morimoto RI (1991) Analysis of the specificity and mechanism of transcriptional activation of the human hsp70 gene during infection by DNA viruses. J Virol 65: 5680-5692
Pockley AG, Shepherd J and Corton JM (1998) Detection of heat shock protein 70 (Hsp70) and anti-Hsp70 antibodies in the serum of normal individuals. Immunol Invest 27: 367-377
Rao DV, Watson K and Jones GL (1999) Age-related attenuation in the expression of the major heat shock proteins in human peripheral lymphocytes. Mech Aging Dev 107: 105-118
Rea IM, McNerlan S and Pockley AG (2001) Serum heat shock protein and anti-heat shock protein antibody levels in aging. Exp Gerontol 36: 341-352
Salotra P, Chauhan D, Ralhan R and Bhatnagar R (1995) Tumour necrosis factor-alpha induces preferential expression of stress proteins in virulent promastigotes of Leishmania donovani. Immunol Lett 44: 1-5
Schett G, Redlich K, Xu Q, Bizan P, Groger M, Tohidast-Akrad M, Kiener H, Smolen J and Steiner G (1998) Enhanced expression of heat shock protein 70 (hsp70) and heat shock factor 1 (HSF1) activation in rheumatoid arthritis synovial tissue. Differential regulation of hsp70 expression and hsf1 activation in synovial fibroblasts by proinflammatory cytokines, shear stress, and anti-inflammatory drugs. J Clin Invest 102: 302-311
Schiaffonati L, Rappocciolo E, Tacchini L, Cairo G and Bernelli-Zazzera A (1990) Reprogramming of gene expression in postischemic rat liver: induction of proto-oncogenes and hsp 70 gene family. J Cell Physiol 143: 79-87
Schoeniger LO, Reilly PM, Bulkley GB and Buchman TG (1992) Heat-shock gene expression excludes hepatic acute-phase gene expression after resuscitation from hemorrhagic shock. Surgery 112: 355-362
Shinnick TM (1991) Heat shock proteins as antigens of bacterial and parasitic pathogens. Curr Top Microbiol Immunol 167: 145-160
Simon RP, Cho H, Gwinn R and Lowenstein DH (1991) The temporal profile of 72-kDa heat-shock protein expression following global ischemia. J Neurosci 11: 881-889
Stephanou A, Isenberg DA, Akira S, Kishimoto T and Latchman DS (1998) The nuclear factor interleukin-6 (NF-IL6) and signal transducer and activator of transcription-3 (STAT-3) signalling pathways co-operate to mediate the activation of the hsp90beta gene by interleukin-6 but have opposite effects on its inducibility by heat shock. Biochem J 330: 189-195
Tamura Y, Peng P, Liu K, Daou M and Srivastava PK (1997) Immunotherapy of tumors with autologous tumor-derived heat shock protein preparations. Science 278: 117-120
Tavaria M, Gabriele T, Kola I and Anderson RL (1996) A hitchhiker's guide to the human Hsp70 family. Cell Stress Chaperones 1: 23-28
Wu B, Gu MJ, Heydari AR and Richardson A (1993) The effect of age on the synthesis of two heat shock proteins in the hsp70 family. J Gerontol 48: 50-56
Xu Q, Li DG, Holbrook NJ and Udelsman R (1995) Acute hypertension induces heat-shock protein 70 gene expression in rat aorta. Circulation 92: 1223-1229
Zugel U, Schoel B, Yamamoto S, Hengel H, Morein B and Kaufmann SH (1995) Crossrecognition by CD8 T cell receptor alpha beta cytotoxic T lymphocytes of peptides in the self and the mycobacterial hsp60 which share intermediate sequence homology. Eur J Immunol 25: 451-458
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Njemini, R., Demanet, C. & Mets, T. Inflammatory status as an important determinant of heat shock protein 70 serum concentrations during aging. Biogerontology 5, 31–38 (2004). https://doi.org/10.1023/B:BGEN.0000017684.15626.29
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DOI: https://doi.org/10.1023/B:BGEN.0000017684.15626.29