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Published in: Immunity & Ageing 1/2018

Open Access 01-12-2018 | Research

NK cells of the oldest seniors represent constant and resistant to stimulation high expression of cellular protective proteins SIRT1 and HSP70

Authors: Lucyna Kaszubowska, Jerzy Foerster, Jan Jacek Kaczor, Daria Schetz, Tomasz Jerzy Ślebioda, Zbigniew Kmieć

Published in: Immunity & Ageing | Issue 1/2018

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Abstract

Background

Natural killer cells (NK cells) are cytotoxic lymphocytes of innate immunity that reveal some immunoregulatory properties, however, their role in the process of ageing is not completely understood. The study aimed to analyze the expression of proteins involved in cellular stress response: sirtuin 1 (SIRT1), heat shock protein 70 (HSP70) and manganese superoxide dismutase (SOD2) in human NK cells with reference to the process of ageing. Non-stimulated and stimulated with IL-2, LPS or PMA with ionomycin cells originated from peripheral blood samples of: seniors aged over 85 (‘the oldest’; n = 25; 88.5 ± 0.5 years, mean ± SEM), seniors aged under 85 (‘the old’; n = 30; 75.6 ± 0.9 years) and the young (n = 31; 20.9 ± 0.3 years). The relationships between the levels of expression of cellular protective proteins in the studied population were also analyzed. The concentrations of carbonyl groups and 8-isoprostanes, markers of oxidative stress, in both stimulated and non-stimulated cultured NK cells were measured to assess the level of the oxidative stress in the cells.

Results

The oldest seniors varied from the other age groups by significantly higher expression of SIRT1 and HSP70 both in non-stimulated and stimulated NK cells. These cells also appeared to be resistant to further stimulations with IL-2, LPS or PMA with ionomycin. Highly positive correlations between SIRT1 and intracellular HSP70 in both stimulated and non-stimulated NK cells were observed. SOD2 presented low expression in non-stimulated cells, whereas its sensitivity to stimulation increased with age of donors. High positive correlations between SOD2 and surface HSP70 were observed. We found that the markers of oxidative stress in NK cells did not change with ageing.

Conclusions

The oldest seniors revealed well developed adaptive stress response in NK cells with increased, constant levels of SIRT1 and intracellular HSP70. They presented also very high positive correlations between expression of these cellular protective proteins both in stimulated and non-stimulated cells. These phenomena may contribute to the long lifespan of this group of elderly. Interestingly, in NK cells SOD2 revealed a distinct role in cellular stress response since it showed sensitivity to stimulation increasing with age of participants. These observations provide novel data concerning the role of NK cells in the process of ageing.
Literature
2.
go back to reference Cording S, Medvedovic J, Aychek T, Eberl G. Innate lymphoid cells in defense, immunopathology and immunotherapy. Nat Immunol. 2016;17:755–7.CrossRefPubMed Cording S, Medvedovic J, Aychek T, Eberl G. Innate lymphoid cells in defense, immunopathology and immunotherapy. Nat Immunol. 2016;17:755–7.CrossRefPubMed
3.
go back to reference Bryceson YT, Chiang SCC, Darmanin S, Fauriat C, Schlums H, Theorell J, Wood SM. Molecular mechanisms of natural killer cell activation. J Innate Immun. 2011;3:216–26.CrossRefPubMed Bryceson YT, Chiang SCC, Darmanin S, Fauriat C, Schlums H, Theorell J, Wood SM. Molecular mechanisms of natural killer cell activation. J Innate Immun. 2011;3:216–26.CrossRefPubMed
4.
go back to reference Hazeldine J, Lord JM. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013;12:1069–78.CrossRefPubMedPubMedCentral Hazeldine J, Lord JM. The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev. 2013;12:1069–78.CrossRefPubMedPubMedCentral
5.
6.
go back to reference Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331:44–9.CrossRefPubMedPubMedCentral Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S. Innate or adaptive immunity? The example of natural killer cells. Science. 2011;331:44–9.CrossRefPubMedPubMedCentral
7.
go back to reference De Maria A, Bozzano F, Cantoni C, Moretta L. Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proc Natl Acad Sci U S A. 2011;108:728–32.CrossRefPubMed De Maria A, Bozzano F, Cantoni C, Moretta L. Revisiting human natural killer cell subset function revealed cytolytic CD56(dim)CD16+ NK cells as rapid producers of abundant IFN-gamma on activation. Proc Natl Acad Sci U S A. 2011;108:728–32.CrossRefPubMed
8.
go back to reference Fauriat C, Long EO, Ljunggren HG, Bryceson YT. Regulation of human NK-cell cytokine and chemokine production by target cell recognition. Blood. 2010;115:2167–76.CrossRefPubMedPubMedCentral Fauriat C, Long EO, Ljunggren HG, Bryceson YT. Regulation of human NK-cell cytokine and chemokine production by target cell recognition. Blood. 2010;115:2167–76.CrossRefPubMedPubMedCentral
9.
go back to reference Mariani E, Meneghetti A, Neri S, Ravaglia G, Forti P, Cattini L, Facchini A. Chemokine production by natural killer cells from nonagenarians. Eur J Immunol. 2002;32:1524–9.CrossRefPubMed Mariani E, Meneghetti A, Neri S, Ravaglia G, Forti P, Cattini L, Facchini A. Chemokine production by natural killer cells from nonagenarians. Eur J Immunol. 2002;32:1524–9.CrossRefPubMed
10.
go back to reference Yu TK, Caudell EG, Smid C, Grimm EA. IL-2 activation of NK cells: involvement of MKK1/2/ERK but not p38 kinase pathway. J Immunol. 2000;164:6244–51.CrossRefPubMed Yu TK, Caudell EG, Smid C, Grimm EA. IL-2 activation of NK cells: involvement of MKK1/2/ERK but not p38 kinase pathway. J Immunol. 2000;164:6244–51.CrossRefPubMed
11.
go back to reference Goodier MR, Londei M. Lipopolysaccharide stimulates the proliferation of human CD56+CD3- NK cells: a regulatory role of monocytes and IL-10. J Immunol. 2000;165:139–47.CrossRefPubMed Goodier MR, Londei M. Lipopolysaccharide stimulates the proliferation of human CD56+CD3- NK cells: a regulatory role of monocytes and IL-10. J Immunol. 2000;165:139–47.CrossRefPubMed
12.
go back to reference Varma TK, Lin CY, Toliver-Kinsky TE, Sherwood ER. Endotoxin-induced gamma interferon production: contributing cell types and key regulatory factors. Clin Diagn Lab Immunol. 2002;9:530–43.PubMedPubMedCentral Varma TK, Lin CY, Toliver-Kinsky TE, Sherwood ER. Endotoxin-induced gamma interferon production: contributing cell types and key regulatory factors. Clin Diagn Lab Immunol. 2002;9:530–43.PubMedPubMedCentral
13.
go back to reference Mian MF, Lauzon NM, Andrews DW, Lichty BD, Ashkar AA. FimH can directly activate human and murine natural killer cells via TLR4. Mol Ther. 2010;18:1379–88.CrossRefPubMedPubMedCentral Mian MF, Lauzon NM, Andrews DW, Lichty BD, Ashkar AA. FimH can directly activate human and murine natural killer cells via TLR4. Mol Ther. 2010;18:1379–88.CrossRefPubMedPubMedCentral
15.
go back to reference Bonizzi G, Karin M. The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25:280–8.CrossRefPubMed Bonizzi G, Karin M. The two NF-κB activation pathways and their role in innate and adaptive immunity. Trends Immunol. 2004;25:280–8.CrossRefPubMed
16.
go back to reference Tamai R, Asai Y, Hashimoto M, Fukase K, Kusumoto S, Ishida H, Kiso M, Ogawa T. Cell activation by monosaccharide lipid a analogues utilizing toll-like receptor 4. Immunology. 2003;110:66–72.CrossRefPubMedPubMedCentral Tamai R, Asai Y, Hashimoto M, Fukase K, Kusumoto S, Ishida H, Kiso M, Ogawa T. Cell activation by monosaccharide lipid a analogues utilizing toll-like receptor 4. Immunology. 2003;110:66–72.CrossRefPubMedPubMedCentral
17.
go back to reference Chopra RK, Nagel JE, Chrest FJ, Adler WH. Impaired phorbol ester and calcium ionophore induced proliferation of T cells from old humans. Clin Exp Immunol. 1987;70:456–62.PubMedPubMedCentral Chopra RK, Nagel JE, Chrest FJ, Adler WH. Impaired phorbol ester and calcium ionophore induced proliferation of T cells from old humans. Clin Exp Immunol. 1987;70:456–62.PubMedPubMedCentral
18.
go back to reference Good SR, Thieu VT, Mathur AN, Yu Q, Stritesky GL, Yeh N, O'Malley JT, Perumal NB, Kaplan MH. Temporal induction pattern of STAT4 target genes defines potential for Th1 lineage-specific programming. J Immunol. 2009;183:3839–47.CrossRefPubMedPubMedCentral Good SR, Thieu VT, Mathur AN, Yu Q, Stritesky GL, Yeh N, O'Malley JT, Perumal NB, Kaplan MH. Temporal induction pattern of STAT4 target genes defines potential for Th1 lineage-specific programming. J Immunol. 2009;183:3839–47.CrossRefPubMedPubMedCentral
19.
go back to reference Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 2014;25:138–45.CrossRefPubMed Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab. 2014;25:138–45.CrossRefPubMed
20.
go back to reference Elpek KG, Rubinstein MP, Bellemare-Pelletier A, Goldrath AW, Turley SJ. Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes. Proc Natl Acad Sci U S A. 2010;107:21647–52.CrossRefPubMedPubMedCentral Elpek KG, Rubinstein MP, Bellemare-Pelletier A, Goldrath AW, Turley SJ. Mature natural killer cells with phenotypic and functional alterations accumulate upon sustained stimulation with IL-15/IL-15Ralpha complexes. Proc Natl Acad Sci U S A. 2010;107:21647–52.CrossRefPubMedPubMedCentral
21.
go back to reference Kaszubowska L, Dettlaff-Pokora A, Hak L, Szarynska M, Ryba M, Mysliwska J, Mysliwski A. Successful ageing of nonagenarians is related to the sensitivity of NK cells to activation. J Physiol Pharmacol. 2008;59(Suppl 9):187–99.PubMed Kaszubowska L, Dettlaff-Pokora A, Hak L, Szarynska M, Ryba M, Mysliwska J, Mysliwski A. Successful ageing of nonagenarians is related to the sensitivity of NK cells to activation. J Physiol Pharmacol. 2008;59(Suppl 9):187–99.PubMed
22.
go back to reference Liu Z, Kharmate G, Patterson E, Khan MM. Role of H1 receptors in histamine-mediated up- regulation of STAT4 phosphorylation. Int Immunopharmacol. 2006;6:485–93.CrossRefPubMed Liu Z, Kharmate G, Patterson E, Khan MM. Role of H1 receptors in histamine-mediated up- regulation of STAT4 phosphorylation. Int Immunopharmacol. 2006;6:485–93.CrossRefPubMed
23.
go back to reference Wendt K, Wilk E, Buyny S, Buer J, Schmidt RE, Jacobs R. Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells. J Leukoc Biol. 2006;80:1529–41.CrossRefPubMed Wendt K, Wilk E, Buyny S, Buer J, Schmidt RE, Jacobs R. Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells. J Leukoc Biol. 2006;80:1529–41.CrossRefPubMed
24.
go back to reference Bueno V, Sant’Anna OA, Lord JM. Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease. Age (Dordr). 2014;36:9729.CrossRef Bueno V, Sant’Anna OA, Lord JM. Ageing and myeloid-derived suppressor cells: possible involvement in immunosenescence and age-related disease. Age (Dordr). 2014;36:9729.CrossRef
25.
go back to reference Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.CrossRefPubMed Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244–54.CrossRefPubMed
27.
go back to reference De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 2009;15:3003–26.CrossRefPubMed De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 2009;15:3003–26.CrossRefPubMed
29.
go back to reference Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizzarelli E, Calabrese EJ. Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochim Biophys Acta. 2012;1822:753–83. Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizzarelli E, Calabrese EJ. Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochim Biophys Acta. 2012;1822:753–83.
30.
go back to reference Hwang JW, Yao H, Caito S, Sundar IK, Rahman I. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med. 2013;61:95–110.CrossRefPubMed Hwang JW, Yao H, Caito S, Sundar IK, Rahman I. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med. 2013;61:95–110.CrossRefPubMed
32.
go back to reference Hensen SM, Heldens L, Van Genesen ST, Pruijn GJ, Lubsen NH. A delayed antioxidant response in heat-stressed cells expressing a non-DNA binding HSF1 mutant. Cell Stress Chaperones. 2013;18:455–73.CrossRefPubMedPubMedCentral Hensen SM, Heldens L, Van Genesen ST, Pruijn GJ, Lubsen NH. A delayed antioxidant response in heat-stressed cells expressing a non-DNA binding HSF1 mutant. Cell Stress Chaperones. 2013;18:455–73.CrossRefPubMedPubMedCentral
33.
go back to reference Östling P, Björk JK, Roos-Mattjus P, Mezger V, Sistonen L. Heat shock factor 2 (HSF2) contributes to inducible expression of hsp genes through interplay with HSF1. J Biol Chem. 2007;282:7077–86.CrossRefPubMed Östling P, Björk JK, Roos-Mattjus P, Mezger V, Sistonen L. Heat shock factor 2 (HSF2) contributes to inducible expression of hsp genes through interplay with HSF1. J Biol Chem. 2007;282:7077–86.CrossRefPubMed
34.
go back to reference Rossi A, Trotta E, Brandi R, Arisi I, Coccia M, Santoro MG. AIRAP, a new human heat shock gene regulated by heat shock factor 1. J Biol Chem. 2010;285:13607–15.CrossRefPubMedPubMedCentral Rossi A, Trotta E, Brandi R, Arisi I, Coccia M, Santoro MG. AIRAP, a new human heat shock gene regulated by heat shock factor 1. J Biol Chem. 2010;285:13607–15.CrossRefPubMedPubMedCentral
35.
go back to reference Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science. 2009;323:1063–6.CrossRefPubMedPubMedCentral Westerheide SD, Anckar J, Stevens SM Jr, Sistonen L, Morimoto RI. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science. 2009;323:1063–6.CrossRefPubMedPubMedCentral
37.
go back to reference Morgan MJ, Liu Z. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2011;21:103–15.CrossRefPubMed Morgan MJ, Liu Z. Crosstalk of reactive oxygen species and NF-κB signaling. Cell Res. 2011;21:103–15.CrossRefPubMed
38.
go back to reference Owczarz M, Budzinska M, Domaszewska-Szostek A, Borkowska J, Polosak J, Gewartowska M, Slusarczyk P, Puzianowska-Kuznicka M. miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans. Exp Biol Med. 2017;242:1453–61.CrossRef Owczarz M, Budzinska M, Domaszewska-Szostek A, Borkowska J, Polosak J, Gewartowska M, Slusarczyk P, Puzianowska-Kuznicka M. miR-34a and miR-9 are overexpressed and SIRT genes are downregulated in peripheral blood mononuclear cells of aging humans. Exp Biol Med. 2017;242:1453–61.CrossRef
39.
go back to reference Kovalenko EI, Boyko AA, Semenkov VF, Lutsenko GV, Grechikhina MV, Kanevskiy LM, Azhikina TL, Telford WG, Sapozhnikov AM. ROS production, intracellular HSP70 levels and their relationship in human neutrophils: effects of age. Oncotarget. 2014;5:11800–12.CrossRefPubMedPubMedCentral Kovalenko EI, Boyko AA, Semenkov VF, Lutsenko GV, Grechikhina MV, Kanevskiy LM, Azhikina TL, Telford WG, Sapozhnikov AM. ROS production, intracellular HSP70 levels and their relationship in human neutrophils: effects of age. Oncotarget. 2014;5:11800–12.CrossRefPubMedPubMedCentral
40.
go back to reference Njemini R, Bautmans I, Lambert M, Demanet C, Mets T. Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation. Mech Ageing Dev. 2007;128:450–4.CrossRefPubMed Njemini R, Bautmans I, Lambert M, Demanet C, Mets T. Heat shock proteins and chemokine/cytokine secretion profile in ageing and inflammation. Mech Ageing Dev. 2007;128:450–4.CrossRefPubMed
41.
go back to reference Singh T, Newman AB. Inflammatory markers in population studies of ageing. Ageing Res Rev. 2011;10:319–29.CrossRefPubMed Singh T, Newman AB. Inflammatory markers in population studies of ageing. Ageing Res Rev. 2011;10:319–29.CrossRefPubMed
42.
go back to reference Gayoso I, Sanchez-Correa B, Campos C, Alonso C, Pera A, Casado JG, Morgado S, Tarazona R, Solana R. Immunosenescence of human natural killer cells. J Innate Immun. 2011;3:337–43.CrossRefPubMed Gayoso I, Sanchez-Correa B, Campos C, Alonso C, Pera A, Casado JG, Morgado S, Tarazona R, Solana R. Immunosenescence of human natural killer cells. J Innate Immun. 2011;3:337–43.CrossRefPubMed
43.
go back to reference Le Garff-Tavernier M, Beziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debré P, Merle-Beral H, Vieillard V. Human NK cells display major phenotypic and functional changes over the lifespan. Aging Cell. 2010;9:527–35.CrossRefPubMed Le Garff-Tavernier M, Beziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debré P, Merle-Beral H, Vieillard V. Human NK cells display major phenotypic and functional changes over the lifespan. Aging Cell. 2010;9:527–35.CrossRefPubMed
44.
go back to reference Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189–98.CrossRefPubMed
45.
go back to reference Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA. 1963;185:914–9.CrossRefPubMed Katz S, Ford AB, Moskowitz RW, Jackson BA, Jaffe MW. Studies of illness in the aged. The index of ADL: a standardized measure of biological and psychosocial function. JAMA. 1963;185:914–9.CrossRefPubMed
46.
go back to reference Kaszubowska L, Foerster J, Kaczor JJ, Schetz D, Ślebioda TJ, Kmieć Z. Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK cells of the oldest seniors. Immun Ageing. 2017;14:3.CrossRefPubMedPubMedCentral Kaszubowska L, Foerster J, Kaczor JJ, Schetz D, Ślebioda TJ, Kmieć Z. Expression of cellular protective proteins SIRT1, HSP70 and SOD2 correlates with age and is significantly higher in NK cells of the oldest seniors. Immun Ageing. 2017;14:3.CrossRefPubMedPubMedCentral
47.
go back to reference Hajek A, König HH. The longitudinal association between informal caregiving and body mass index in the second half of life: findings of the German ageing survey. Public Health. 2017;151:81–6.CrossRefPubMed Hajek A, König HH. The longitudinal association between informal caregiving and body mass index in the second half of life: findings of the German ageing survey. Public Health. 2017;151:81–6.CrossRefPubMed
50.
go back to reference Halliwell B. Oxidative stress in cell culture: an under-appreciated problem? FEBS Lett. 2003;540:3–6.CrossRefPubMed Halliwell B. Oxidative stress in cell culture: an under-appreciated problem? FEBS Lett. 2003;540:3–6.CrossRefPubMed
51.
go back to reference Chen X, Lu Y, Zhang Z, Wang J, Yang H, Liu G. Intercellular interplay between Sirt1 signalling and cell metabolism in immune cell biology. Immunology. 2015;145:455–67.CrossRefPubMedPubMedCentral Chen X, Lu Y, Zhang Z, Wang J, Yang H, Liu G. Intercellular interplay between Sirt1 signalling and cell metabolism in immune cell biology. Immunology. 2015;145:455–67.CrossRefPubMedPubMedCentral
52.
go back to reference Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF- kB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal. 2013;25:1939–48.CrossRefPubMed Kauppinen A, Suuronen T, Ojala J, Kaarniranta K, Salminen A. Antagonistic crosstalk between NF- kB and SIRT1 in the regulation of inflammation and metabolic disorders. Cell Signal. 2013;25:1939–48.CrossRefPubMed
53.
go back to reference Wang YQ, Cao Q, Wang F, Huang LY, Sang TT, Liu F, Chen SY. SIRT1 protects against oxidative stress-induced endothelial progenitor cells apoptosis by inhibiting FOXO3a via FOXO3a ubiquitination and degradation. J Cell Physiol. 2015;230:2098–107.CrossRefPubMed Wang YQ, Cao Q, Wang F, Huang LY, Sang TT, Liu F, Chen SY. SIRT1 protects against oxidative stress-induced endothelial progenitor cells apoptosis by inhibiting FOXO3a via FOXO3a ubiquitination and degradation. J Cell Physiol. 2015;230:2098–107.CrossRefPubMed
54.
go back to reference Belloni L, Pollicino T, De Nicola F, Guerrieri F, Raffa G, Fanciulli M, Raimondo G, Levrero M. Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc Natl Acad Sci U S A. 2009;106:19975–9.CrossRefPubMedPubMedCentral Belloni L, Pollicino T, De Nicola F, Guerrieri F, Raffa G, Fanciulli M, Raimondo G, Levrero M. Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function. Proc Natl Acad Sci U S A. 2009;106:19975–9.CrossRefPubMedPubMedCentral
55.
go back to reference Yun JM, Chien A, Jialal I, Devaraj S. Resveratrol up-regulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights. J Nutr Biochem. 2012;23:699–705.CrossRefPubMed Yun JM, Chien A, Jialal I, Devaraj S. Resveratrol up-regulates SIRT1 and inhibits cellular oxidative stress in the diabetic milieu: mechanistic insights. J Nutr Biochem. 2012;23:699–705.CrossRefPubMed
56.
57.
go back to reference Kamiński MM, Röth D, Sass S, Sauer SW, Krammer PH, Gülow K. Manganese superoxide dismutase: a regulator of T cell activation-induced oxidative signaling and cell death. Biochim Biophys Acta. 1823;2012:1041–52. Kamiński MM, Röth D, Sass S, Sauer SW, Krammer PH, Gülow K. Manganese superoxide dismutase: a regulator of T cell activation-induced oxidative signaling and cell death. Biochim Biophys Acta. 1823;2012:1041–52.
58.
go back to reference Kaszubowska L, Wierzbicki PM, Karsznia S, Damska M, Ślebioda TJ, Foerster J, Kmieć Z. Optimal reference genes for qPCR in resting and activated human NK cells--flow cytometric data correspond to qPCR gene expression analysis. J Immunol Methods. 2015;422:125–9.CrossRefPubMed Kaszubowska L, Wierzbicki PM, Karsznia S, Damska M, Ślebioda TJ, Foerster J, Kmieć Z. Optimal reference genes for qPCR in resting and activated human NK cells--flow cytometric data correspond to qPCR gene expression analysis. J Immunol Methods. 2015;422:125–9.CrossRefPubMed
59.
go back to reference Multhoff G, Hightower LE. Distinguishing integral and receptor-bound heat shock protein 70 (Hsp70) on the cell surface by Hsp70-specific antibodies. Cell Stress Chaperones. 2011;16:251–5.CrossRefPubMed Multhoff G, Hightower LE. Distinguishing integral and receptor-bound heat shock protein 70 (Hsp70) on the cell surface by Hsp70-specific antibodies. Cell Stress Chaperones. 2011;16:251–5.CrossRefPubMed
60.
go back to reference Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R. Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol. 1993;23:2375–8.CrossRefPubMed Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R. Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol. 1993;23:2375–8.CrossRefPubMed
61.
go back to reference Hayhoe RP, Henson SM, Akbar AN, Palmer DB. Variation of human natural killer cell phenotypes with age: identification of a unique KLRG1-negative subset. Hum Immunol. 2010;71:676–81.CrossRefPubMed Hayhoe RP, Henson SM, Akbar AN, Palmer DB. Variation of human natural killer cell phenotypes with age: identification of a unique KLRG1-negative subset. Hum Immunol. 2010;71:676–81.CrossRefPubMed
62.
go back to reference Krishnaraj R. Senescence and cytokines modulate the NK cell expression. Mech Ageing Dev. 1997;96:89–101.CrossRefPubMed Krishnaraj R. Senescence and cytokines modulate the NK cell expression. Mech Ageing Dev. 1997;96:89–101.CrossRefPubMed
64.
go back to reference Sitte N, Merker K, Grune T. Proteasome-dependent degradation of oxidized proteins in MRC-5 fibroblasts. FEBS Lett. 1998;440:399–402.CrossRefPubMed Sitte N, Merker K, Grune T. Proteasome-dependent degradation of oxidized proteins in MRC-5 fibroblasts. FEBS Lett. 1998;440:399–402.CrossRefPubMed
65.
go back to reference Adams S, Green P, Claxton R, Simcox S, Williams MV, Walsh K, Leeuwenburgh C. Reactive carbonyl formation by oxidative and non-oxidative pathways. Front Biosci. 2001;6:A17–24.CrossRefPubMed Adams S, Green P, Claxton R, Simcox S, Williams MV, Walsh K, Leeuwenburgh C. Reactive carbonyl formation by oxidative and non-oxidative pathways. Front Biosci. 2001;6:A17–24.CrossRefPubMed
66.
go back to reference Van ‘t Erve TJ, Kadiiska MB, London SJ, Mason RP. Classifying oxidative stress by F2-isoprostane levels across human diseases: a meta-analysis. Redox Biol. 2017;12:582–99.CrossRefPubMedPubMedCentral Van ‘t Erve TJ, Kadiiska MB, London SJ, Mason RP. Classifying oxidative stress by F2-isoprostane levels across human diseases: a meta-analysis. Redox Biol. 2017;12:582–99.CrossRefPubMedPubMedCentral
67.
go back to reference Hagen TM. Oxidative stress, redox imbalance, and the aging process. Antioxid Redox Signal. 2003;5:503–6.CrossRefPubMed Hagen TM. Oxidative stress, redox imbalance, and the aging process. Antioxid Redox Signal. 2003;5:503–6.CrossRefPubMed
68.
go back to reference Ristow M, Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol. 2010;45:410–8.CrossRefPubMed Ristow M, Zarse K. How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol. 2010;45:410–8.CrossRefPubMed
69.
go back to reference Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med. 2011;51:327–36.CrossRefPubMed Ristow M, Schmeisser S. Extending life span by increasing oxidative stress. Free Radic Biol Med. 2011;51:327–36.CrossRefPubMed
70.
go back to reference Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303:2011–5.CrossRefPubMed Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. Science. 2004;303:2011–5.CrossRefPubMed
71.
go back to reference Katto J, Engel N, Abbas W, Herbein G, Mahlknecht U. Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1. Clin Epigenetics. 2013;5:11.CrossRefPubMedPubMedCentral Katto J, Engel N, Abbas W, Herbein G, Mahlknecht U. Transcription factor NFκB regulates the expression of the histone deacetylase SIRT1. Clin Epigenetics. 2013;5:11.CrossRefPubMedPubMedCentral
72.
go back to reference Yang H, Zhang W, Pan H, Feldser HG, Lainez E, Miller C, Leung S, Zhong Z, Zhao H, Sweitzer S, Considine T, Riera T, Suri V, White B, Ellis JL, Vlasuk GP, Loh C. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-κB activity. PLoS One. 2012;7:e46364.CrossRefPubMedPubMedCentral Yang H, Zhang W, Pan H, Feldser HG, Lainez E, Miller C, Leung S, Zhong Z, Zhao H, Sweitzer S, Considine T, Riera T, Suri V, White B, Ellis JL, Vlasuk GP, Loh C. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-κB activity. PLoS One. 2012;7:e46364.CrossRefPubMedPubMedCentral
73.
go back to reference Nakayama A, Kawasaki H, Jin C, Munekata E, Taira K, Yokoyama KK. Transcriptional regulation of interferon gamma gene by p300 co-activator. Nucleic Acids Res Suppl. 2001;1:89–90.CrossRef Nakayama A, Kawasaki H, Jin C, Munekata E, Taira K, Yokoyama KK. Transcriptional regulation of interferon gamma gene by p300 co-activator. Nucleic Acids Res Suppl. 2001;1:89–90.CrossRef
74.
go back to reference Kilic U, Gok O, Erenberk U, Dundaroz MR, Torun E, Kucukardali Y, Elibol-Can B, Uysal O, Dundar T. A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PLoS One. 2015;10:e0117954.CrossRefPubMedPubMedCentral Kilic U, Gok O, Erenberk U, Dundaroz MR, Torun E, Kucukardali Y, Elibol-Can B, Uysal O, Dundar T. A remarkable age-related increase in SIRT1 protein expression against oxidative stress in elderly: SIRT1 gene variants and longevity in human. PLoS One. 2015;10:e0117954.CrossRefPubMedPubMedCentral
75.
go back to reference Kaszubowska L, Kaczor JJ, Hak L, Dettlaff-Pokora A, Szarynska M, Kmiec Z. Sensitivity of natural killer cells to activation in the process of ageing is related to the oxidative and inflammatory status of the elderly. J Physiol Pharmacol. 2011;62:101–9.PubMed Kaszubowska L, Kaczor JJ, Hak L, Dettlaff-Pokora A, Szarynska M, Kmiec Z. Sensitivity of natural killer cells to activation in the process of ageing is related to the oxidative and inflammatory status of the elderly. J Physiol Pharmacol. 2011;62:101–9.PubMed
76.
go back to reference Liu DJ, Hammer D, Komlos D, Chen KY, Firestein BL, Liu AY. SIRT1 knockdown promotes neural differentiation and attenuates the heat shock response. J Cell Physiol. 2014;229:1224–35.CrossRefPubMed Liu DJ, Hammer D, Komlos D, Chen KY, Firestein BL, Liu AY. SIRT1 knockdown promotes neural differentiation and attenuates the heat shock response. J Cell Physiol. 2014;229:1224–35.CrossRefPubMed
Metadata
Title
NK cells of the oldest seniors represent constant and resistant to stimulation high expression of cellular protective proteins SIRT1 and HSP70
Authors
Lucyna Kaszubowska
Jerzy Foerster
Jan Jacek Kaczor
Daria Schetz
Tomasz Jerzy Ślebioda
Zbigniew Kmieć
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Immunity & Ageing / Issue 1/2018
Electronic ISSN: 1742-4933
DOI
https://doi.org/10.1186/s12979-018-0115-x

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