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COPD and levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes among coal workers: a case-control study

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Cell Stress and Chaperones Aims and scope

A Letter to the Editor to this article was published on 04 August 2015

A Letter to the Editor to this article was published on 21 July 2015

Abstract

This case-control study aimed to investigate whether the levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes were associated with the risk of chronic obstructive pulmonary disease (COPD) among coal workers. A total of 76 COPD cases and 48 age-matched healthy controls from a group of coal workers were included. The case group consisted of 35 COPD patients whose condition was complicated with coal workers’ pneumoconiosis (CWP) and 41 COPD patients without CWP. Heat shock proteins (Hsps) in plasma and lymphocytes were detected by ELISA and flow cytometry, respectively. Multiple logistic regression models were applied to estimate the association between Hsp levels and COPD risk. Our results showed that plasma Hsp70 and lymphocyte Hsp27 levels were significantly higher and plasma Hsp27 levels were significantly lower in COPD cases than in controls (p < 0.01). No significant differences in lymphocyte Hsp70 levels were found between COPD cases and the matched subjects. Higher plasma Hsp70 levels (odds ratio (OR) = 13.8, 95 % confidence interval (CI) = 5.7–33.5) and lower plasma Hsp27 levels (OR = 4.6, 95 % CI = 2.0–10.5) were significantly associated with an increased risk of COPD after adjusting for confounders. Higher lymphocyte Hsp27 levels were only associated with an increased risk of COPD with CWP (OR = 6.6, 95 % CI = 2.0–22.1) but not with an increased risk of COPD without CWP (OR = 3.0, 95 % CI = 0.9–8.9). Additionally, there were strong joint effects of different Hsps on COPD risk. These results showed that higher levels of plasma Hsp70 and lower levels of plasma Hsp27 might be associated with an increased risk of COPD among coal workers. They may have the potential to serve as monitoring markers for COPD in coal workers.

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References

  • Abboud R, Vimalanathan S (2008) Pathogenesis of COPD. Part I. The role of protease-antiprotease imbalance in emphysema [State of the Art Series. Chronic obstructive pulmonary disease in high-and low-income countries. Edited by G. Marks and M. Chan-Yeung. Number 3 in the series]. Int J Tuberc Lung Dis 12(4):361–367

    CAS  PubMed  Google Scholar 

  • Agustı A, Noguera A, Sauleda J, Sala E, Pons J, Busquets X (2003) Systemic effects of chronic obstructive pulmonary disease. Eur Respir J 21(2):347–360

    Article  PubMed  Google Scholar 

  • Arrigo AP (2007) The cellular "networking" of mammalian Hsp27 and its functions in the control of protein folding, redox state and apoptosis. Adv Exp Med Biol 594:14–26. doi:10.1007/978-0-387-39975-1_2

    Article  PubMed  Google Scholar 

  • Asea A, Kraeft S-K, 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(4):435–442

    Article  CAS  PubMed  Google Scholar 

  • Asea A, Rehli M, Kabingu E, Boch JA, Baré 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(17):15028–15034

    Article  CAS  PubMed  Google Scholar 

  • Bachelet M, Mariéthoz E, Banzet N, Souil E, Pinot F, Pollal CZ, Durand P, Bouchaert I, Polla BS (1998) Flow cytometry is a rapid and reliable method for evaluating heat shock protein 70 expression in human monocytes. Cell Stress Chaperones 3(3):168

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bøyum A (1976) Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol 5(s5):9–15

    Article  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

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Castranova V, Vallyathan V (2000) Silicosis and coal workers' pneumoconiosis. Environ Health Perspect 108(Suppl 4):675

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen W, Zhuang Z, Attfield M, Chen B, Gao P, Harrison J, Fu C, Chen J, Wallace W (2001) Exposure to silica and silicosis among tin miners in China: exposure-response analyses and risk assessment. Occup Environ Med 58(1):31–37

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen W, Liu Y, Wang H, Hnizdo E, Sun Y, Su L, Zhang X, Weng S, Bochmann F, Hearl FJ (2012) Long-term exposure to silica dust and risk of total and cause-specific mortality in Chinese workers: a cohort study. PLoS Med 9(4):e1001206

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chung K, Adcock I (2008) Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J 31(6):1334–1356

    Article  CAS  PubMed  Google Scholar 

  • De AK, Kodys KM, Yeh BS, Miller-Graziano C (2000) Exaggerated human monocyte IL-10 concomitant to minimal TNF-α induction by heat-shock protein 27 (Hsp27) suggests Hsp27 is primarily an antiinflammatory stimulus. J Immunol 165(7):3951–3958

    Article  CAS  PubMed  Google Scholar 

  • Dong J, Guo L, Liao Z, Zhang M, Zhang M, Wang T, Chen L, Xu D, Feng Y, Wen F (2013) Increased expression of heat shock protein 70 in chronic obstructive pulmonary disease. Int Immunopharmacol 17(3):885–893

    Article  CAS  PubMed  Google Scholar 

  • Gan W, Man S, Senthilselvan A, Sin D (2004) Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis. Thorax 59(7):574–580

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Gómez FP, Rodriguez-Roisin R (2002) Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for chronic obstructive pulmonary disease. Curr Opin Pulm Med 8(2):81–86

    Article  PubMed  Google Scholar 

  • Gosset P, Lassalle P, Vanhee D, Wallaert B, Aerts C, Voisin C, Tonnel AB (1991) Production of tumor necrosis factor-alpha and interleukin-6 by human alveolar macrophages exposed in vitro to coal mine dust. Am J Respir Cell Mol Biol 5(5):431–436. doi:10.1165/ajrcmb/5.5.431

    Article  CAS  PubMed  Google Scholar 

  • Gruden G, Barutta F, Catto I, Bosco G, Caprioli MG, Pinach S, Fornengo P, Cavallo-Perin P, Davini O, Cerrato P (2013) Serum levels of heat shock protein 27 in patients with acute ischemic stroke. Cell Stress Chaperones 18(4):531–533

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hacker S, Lambers C, Hoetzenecker K, Pollreisz A, Aigner C, Lichtenauer M, Mangold A, Niederpold T, Zimmermann M, Taghavi S (2009) Elevated HSP27, HSP70 and HSP90 alpha in chronic obstructive pulmonary disease: markers for immune activation and tissue destruction. Clin Lab 55(1–2):31–40

    CAS  PubMed  Google Scholar 

  • Hendrick JP, Hartl F (1993) Molecular chaperone functions of heat-shock proteins. Annu Rev Biochem 62(1):349–384

    Article  CAS  PubMed  Google Scholar 

  • Hino M, Kurogi K, Okubo MA, Murata-Hori M, Hosoya H (2000) Small heat shock protein 27 (HSP27) associates with tubulin/microtubules in HeLa cells. Biochem Biophys Res Commun 271(1):164–169. doi:10.1006/bbrc.2000.2553

    Article  CAS  PubMed  Google Scholar 

  • Jan Ankersmit H, Nickl S, Hoeltl E, Toepker M, Lambers C, Mitterbauer A, Kortuem B, Zimmermann M, Moser B, Bekos C, Steinlechner B, Hofbauer H, Klepetko W, Schenk P, Dome B (2012) Increased serum levels of HSP27 as a marker for incipient chronic obstructive pulmonary disease in young smokers. Respiration 83(5):391–399. doi:10.1159/000336557

    PubMed  Google Scholar 

  • Júnior SÁ, Possamai F, Budni P, Backes P, Parisotto E, Rizelio V, Torres M, Colepicolo P, Wilhelm Filho D (2009) Occupational airborne contamination in south Brazil: 1. Oxidative stress detected in the blood of coal miners. Ecotoxicology 18(8):1150–1157

    Article  Google Scholar 

  • Kuempel ED, Stayner LT, Attfield MD, Buncher CR (1995) Exposure‐response analysis of mortality among coal miners in the United States. Am J Ind Med 28(2):167–184

    Article  CAS  PubMed  Google Scholar 

  • Kuempel ED, Wheeler MW, Smith RJ, Vallyathan V, Green FH (2009) Contributions of dust exposure and cigarette smoking to emphysema severity in coal miners in the United States. Am J Respir Crit Care Med 180(3):257–264

    Article  PubMed  Google Scholar 

  • Lancaster G, Møller K, Nielsen B, Secher NH, Febbraio MA, Nybo L (2004) Exercise induces the release of heat shock protein 72 from the human brain in vivo. Cell Stress Chaperones 9(3):276

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lindquist S, Craig E (1988) The heat-shock proteins. Annu Rev Genet 22(1):631–677

    Article  CAS  PubMed  Google Scholar 

  • MacNee W, Rahman I (2001) Is oxidative stress central to the pathogenesis of chronic obstructive pulmonary disease? Trends Mol Med 7(2):55–62

    Article  CAS  PubMed  Google Scholar 

  • Mannino DM, Buist AS (2007) Global burden of COPD: risk factors, prevalence, and future trends. Lancet 370(9589):765–773

    Article  PubMed  Google Scholar 

  • Martin-Ventura JL, Nicolas V, Houard X, Blanco-Colio LM, Leclercq A, Egido J, Vranckx R, Michel J-B, Meilhac O (2006) Biological significance of decreased HSP27 in human atherosclerosis. Arterioscler Thromb Vasc Biol 26(6):1337–1343

    Article  CAS  PubMed  Google Scholar 

  • Meijers J, Swaen G, Slangen J (1997) Mortality of Dutch coal miners in relation to pneumoconiosis, chronic obstructive pulmonary disease, and lung function. Occup Environ Med 54(10):708–713

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Miller B, Jacobsen M (1985) Dust exposure, pneumoconiosis, and mortality of coalminers. Br J Ind Med 42(11):723–733

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R, Viegi G, Wanger J (2005) Standardisation of spirometry. Eur Respir J 26(2):319–338. doi:10.1183/09031936.05.00034805

    Article  CAS  PubMed  Google Scholar 

  • Morfeld PB, Schins RPF, Lenaerts H, Witte B, Derwall R, Piekarski C (2001) Cross sectional study on cytokine production (TNF-α, IL-8) in German coalminers with progressive massive fibrosis and in control miners using a rapid wholeblood assay. Biomarkers 6(6):428–439

    Article  CAS  Google Scholar 

  • Morteza A, Nakhjavani M, Larry M, Nargesi AA, Esteghamati A (2013) Heat shock protein 70 and albuminuria in patients with type 2 diabetes: a matched case control study. Cell Stress Chaperones 18(6):815–819

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Nicks ME, O'Brien MM, Bowler RP (2011) Plasma antioxidants are associated with impaired lung function and COPD exacerbations in smokers. COPD 8(4):264–269. doi:10.3109/15412555.2011.579202

    Article  PubMed Central  PubMed  Google Scholar 

  • Njemini R, Lambert M, Demanet C, Mets T (2006) The effect of aging and inflammation on heat shock protein 27 in human monocytes and lymphocytes. Exp Gerontol 41(3):312–319

    Article  CAS  PubMed  Google Scholar 

  • Oudijk ED, Lammers JJ, Koenderman L (2003) Systemic inflammation in chronic obstructive pulmonary disease. Eur Respir J 22(46 suppl):5s–13s

    Article  CAS  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 

  • Pockley AG (2003) Heat shock proteins as regulators of the immune response. Lancet 362(9382):469–476

    Article  CAS  PubMed  Google Scholar 

  • Rahman I, Morrison D, Donaldson K, MacNee W (1996) Systemic oxidative stress in asthma, COPD, and smokers. Am J Respir Crit Care Med 154(4):1055–1060

    Article  CAS  PubMed  Google Scholar 

  • Rogalla T, Ehrnsperger M, Preville X, Kotlyarov A, Lutsch G, Ducasse C, Paul C, Wieske M, Arrigo A-P, Buchner J (1999) Regulation of Hsp27 oligomerization, chaperone function, and protective activity against oxidative stress/tumor necrosis factor α by phosphorylation. J Biol Chem 274(27):18947–18956

    Article  CAS  PubMed  Google Scholar 

  • Saetta M, Di Stefano A, Maestrelli P, Ferraresso A, Drigo R, Potena A, Ciaccia A, Fabbri LM (1993) Activated T-lymphocytes and macrophages in bronchial mucosa of subjects with chronic bronchitis. Am Rev Respir Dis 147(2):301–306

    Article  CAS  PubMed  Google Scholar 

  • Salari S, Seibert T, Chen Y-X, Hu T, Shi C, Zhao X, Cuerrier CM, Raizman JE, O’Brien ER (2013) Extracellular HSP27 acts as a signaling molecule to activate NF-κB in macrophages. Cell Stress Chaperones 18(1):53–63

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Seibert TA, Hibbert B, Chen YX, Rayner K, Simard T, Hu T, Cuerrier CM, Zhao X, de Belleroche J, Chow BJ, Hawken S, Wilson KR, O'Brien ER (2013) Serum heat shock protein 27 levels represent a potential therapeutic target for atherosclerosis: observations from a human cohort and treatment of female mice. J Am Coll Cardiol 62(16):1446–1454. doi:10.1016/j.jacc.2013.05.041

    Article  CAS  PubMed  Google Scholar 

  • Serneri G, Abbate R, Gori A, Attanasio M, Martini F, Giusti B, Dabizzi P, Poggesi L, Modesti P, Trotta F (1992) Transient intermittent lymphocyte activation is responsible for the instability of angina. Circulation 86(3):790–797

    Article  CAS  PubMed  Google Scholar 

  • Srivastava P (2002) Interaction of heat shock proteins with peptides and antigen presenting cells: chaperoning of the innate and adaptive immune responses. Annu Rev Immunol 20(1):395–425

    Article  CAS  PubMed  Google Scholar 

  • Vega VL, Rodríguez-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(6):4299–4307

    Article  CAS  PubMed  Google Scholar 

  • Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, Barnes PJ, Fabbri LM, Martinez FJ, Nishimura M, Stockley RA, Sin DD, Rodriguez-Roisin R (2013) Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med 187(4):347–365. doi:10.1164/rccm.201204-0596PP

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Feng M, Xu P, Xiao H, Niu P, Yang X, Bai Y, Peng Y, Yao P, Tan H (2009) The level of Hsp27 in lymphocytes is negatively associated with a higher risk of lung cancer. Cell Stress Chaperones 14(3):245–251

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang H, Xing J, Wang F, Han W, Ren H, Wu T, Chen W (2010) Expression of Hsp27 and Hsp70 in lymphocytes and plasma in healthy workers and coal miners with lung cancer. Huazhong Univ Science and Technolog Med Sci 30:415–420

    Article  CAS  Google Scholar 

  • Xiao C, Wu T, Ren A, Pan Q, Chen S, Wu F, Li X, Wang R, Hightower LE, Tanguay RM (2003) Basal and inducible levels of Hsp70 in patients with acute heat illness induced during training. Cell Stress Chaperones 8(1):86–92

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang X, Xu Z, Zhou L, Chen Y, He M, Cheng L, Hu FB, Tanguay RM, Wu T (2010) Plasma levels of Hsp70 and anti-Hsp70 antibody predict risk of acute coronary syndrome. Cell Stress Chaperones 15(5):675–686

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

We are particularly grateful to all individuals who voluntarily participated in the study and to the doctors in the Central Hospital of Xishan Coal & Power Company for their generous help in the health examination and sampling of subjects. This study was supported by research funds from the National Basic Research Program of China (2011CB503804) and the National Natural Science Foundation of China (81372967).

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Authors and Affiliations

  1. Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xiuqing Cui, Yuewei Liu, Yun Zhou, Xin Luo, Zhihong Zhang, Tangchun Wu & Weihong Chen

  2. Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

    Xiuqing Cui, Jingcai Xing, Yuewei Liu, Yun Zhou, Xin Luo, Zhihong Zhang, Tangchun Wu & Weihong Chen

  3. Department of Respiratory Diseases of the General Hospital of Xishan Coal & Power Group, Co. Ltd., Shanxi, 030053, China

    Jingcai Xing & Wenhui Han

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  1. Xiuqing Cui
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Cui, X., Xing, J., Liu, Y. et al. COPD and levels of Hsp70 (HSPA1A) and Hsp27 (HSPB1) in plasma and lymphocytes among coal workers: a case-control study. Cell Stress and Chaperones 20, 473–481 (2015). https://doi.org/10.1007/s12192-015-0572-5

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