Skip to main content
SpringerLink
Log in

Heat shock protein 10 of Chlamydophila pneumoniae induces proinflammatory cytokines through Toll-like receptor (TLR) 2 and TLR4 in human monocytes THP-1

  • Published:
In Vitro Cellular & Developmental Biology - Animal Aims and scope Submit manuscript

Abstract

Inflammatory response is the first line of infection. Previous studies have suggested that Chlamydophila pneumoniae heat shock protein (CHSP) 60 is present in human atheromata, and it plays an important role on the chronic infection elicited by C. pneumoniae. Here, we demonstrated in vitro the impact of heat shock protein 10 (HSP10) of C. pneumoniae on THP-1 cells and the role of Toll-like receptors (TLRs) in the procedures of inflammatory response. The production of proinflammatory cytokines, including tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-6, and IL-1beta were induced by recombinant HSP10 dose-dependently, and the proinflammatory activity of HSP10 was greatly reduced by heating and deproteinization treatment. The expression of TLR4 and TLR2 on the cultured cells were determined by reverse transcriptase-polymerase chain reaction and immunofluorescence. Peritoneal macrophages isolated from wild-type (C3H/HeN) and TLR4-deficient mice (C3H/HeJ) were respectively stimulated with endotoxin-free proteins. Cytokine responses after stimulation were significantly different, depending on the presence of TLR4. The effect on cytokine expression was blocked by anti-TLR2 or anti-TLR4 MAb partially or dramatically. Thus, HSP10 of C. pneumoniae which could elicit inflammatory reactions in human monocytes may contribute to the inflammatory processes in Chlamydophila infection, and the effects were mediated by TLR4 and, to a lesser extent, TLR2.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1.
Figure 2.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
Figure 8.

Similar content being viewed by others

References

  • Blasi F.; Tarsia P.; Aliberti S. Chlamydophila pneumoniae. Clin. Microbiol. Infect. 15: 29–35; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Blessing E.; Lin T. M.; Campbell L. A.; Rosenfeld M. E.; Lloyd D.; Kuo C. Chlamydia pneumoniae induces inflammatory changes in the heart and aorta of normocholesterolemic C57BL/6 J mice. Infect. Immu. 68: 4765–4768; 2000.

    Article  CAS  Google Scholar 

  • Betsou F.; Sueur J. M.; Orfila J. Serological investigation of Chlamydia trachomatis heat shock protein 10. Infect. Immun. 67: 5243–5246; 1999.

    PubMed  CAS  Google Scholar 

  • Betsou F.; Sueur J. M.; Orfila J. Anti-Chlamydia pneumoniae heat shock protein 10 antibodies in asthmatic adults. FEMS. Immunol. Med. Microbiol. 35: 107–111; 2003.

    Google Scholar 

  • Bulut Y.; Faure E.; Thomas L.; Karahashi H.; Michelsen K. S.; Equils O.; Morrison S. G.; Morrison R. P.; Arditi M. Chlamydial heat shock protein 60 activates macrophages and endothelial cells through Toll-like receptor 4 and MD2 in a MyD88-dependent pathway. J. Immunol. 168: 1435–1440; 2002.

    PubMed  CAS  Google Scholar 

  • Cheng W.; Shivshankar P.; Zhong Y.; Chen D.; Li Z.; Zhong G. Intracellular interleukin-1alpha mediates interleukin-8 production induced by Chlamydia trachomatis infection via a mechanism independent of type I interleukin-1 receptor. Infect. Immun. 76: 942–951; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Cook P. J. Antimicrobial therapy for Chlamydia pneumoniae: its potential role in atherosclerosis and asthma. J. Antimicrob. Chemother. 44: 145–148; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Cosentini R.; Tarsia P.; Canetta C.; Graziadei G.; Brambilla A. M.; Aliberti S.; Pappalettera M.; Tantardini F.; Blasi F. Severe asthma exacerbation: role of acute Chlamydophila pneumoniae and Mycoplasma pneumoniae infection. Respir. Res. 9: 48; 2008.

    Article  PubMed  Google Scholar 

  • Davidson M.; Kuo C. C.; Middaugh J. P.; Campbell L. A.; Wang S. P.; Newman W. P.; Finley J. C.; Grayston J. T. Confirmed previous infection with Chlamydia pneumoniae (TWAR) and its presence in early coronary atherosclerosis. Circulation. 98: 628–633; 1998.

    PubMed  CAS  Google Scholar 

  • Didion S. P. Chlamydophila pneumoniae and endothelial activation: the smoke that precedes the fire of atherosclerosis? Circ. Res. 102: 861–863; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Fossati G.; Izzo G.; Rizzi E.; Gancia E.; Modena D.; Moras M. L.; Niccolai N.; Giannozzi E.; Spiga O.; Bono L.; Marone P.; Leone E.; Mangili F.; Harding S.; Errington N.; Walters C.; Henderson B.; Roberts M. M.; Coates A. R.; Casetta B.; Mascagni P. Mycobacterium tuberculosis chaperonin 10 is secreted in the macrophage phagosome: is secretion due to dissociation and adoption of a partially helical structure at the membrane? J. Bacteriol. 185: 4256–4267; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Faure E.; Equils O.; Sieling P. A.; Thomas L.; Zhang F. X.; Kirschning C. J.; Polentarutti N.; Muzio M.; Arditi M. Bacterial lipopolysaccharide activates NF-kappaB through toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells. Differential expression of TLR-4 and TLR-2 in endothelial cells. J. Biol. Chem. 275: 11058–11063; 2000.

    Google Scholar 

  • Gao B.; Wang Y.; Tsan M. F. The heat sensitivity of cytokine-inducing effect of lipopolysaccharide. J. Leukoc. Biol. 80: 359–366; 2006.

    Article  PubMed  CAS  Google Scholar 

  • Grayston J. T.; Aldous M. B.; Easton A.; Wang S. P.; Kuo C. C.; Campbell L. A.; Altman J. Evidence that Chlamydia pneumoniae causes pneumonia and bronchitis. J. Infect. Dis. 168: 1231–1235; 1993.

    Article  PubMed  CAS  Google Scholar 

  • Hahn D. L.; Bukstein D.; Luskin A.; Zeitz H. Evidence for Chlamydia pneumoniae infection in steroid-dependent asthma. Ann. Allergy. Asthma. Immunol. 80: 45–49; 1998.

    Article  PubMed  CAS  Google Scholar 

  • Henderson B.; Pockley A. G. Molecular chaperones and protein-folding catalysts as intercellular signaling regulators in immunity and inflammation. J. Leukoc. Biol. 88: 445–462; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Huang Q. Q.; Sobkoviak R.; Jockheck-Clark A. R.; Shi B.; Mandelin A. M.; Tak P. P.; Haines 3rd G. K.; Nicchitta C. V.; Pope R. M. Heat shock protein 96 is elevated in rheumatoid arthritis and activates macrophages primarily via TLR2 signaling. J. Immunol. 182: 4965–4973; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Jha H. C.; Srivastava P.; Divya A.; Prasad J.; Mittal A. Prevalence of Chlamydophila pneumoniae is higher in aorta and coronary artery than in carotid artery of coronary artery disease patients. APMIS. 117: 905–911; 2009.

    Article  PubMed  CAS  Google Scholar 

  • Jha R.; Vardhan H.; Bas S.; Salhan S.; Mittal A. Chlamydia trachomatis heat shock proteins 60 and 10 induce apoptosis in endocervical epithelial cells. Inflamm. Res. 60: 69–78; 2010.

    Article  PubMed  Google Scholar 

  • Jia H. B.; Halilou A. I.; Hu L.; Cai W. Q.; Liu J.; Huang B. Heat shock protein 10 (Hsp10) in immune-related diseases: one coin, two sides. Int. J. Biochem. Mol. Biol. 2: 47–57; 2011.

    CAS  Google Scholar 

  • Jiang S. J.; Kuo C. C.; Berry M. W.; Lee A. W.; Campbell L. A. Identification and characterization of Chlamydia pneumoniae-specific proteins that activate tumor necrosis factor alpha production in RAW 264.7 murine macrophages. Infect. Immun. 76: 1558–1564; 2008.

    Article  PubMed  CAS  Google Scholar 

  • Kol A. T.; Bourcier A. H.; Lichtman P.; Libby D. Chlamydial heat shock protein 60 localizes in human atheroma and regulates macrophage tumor necrosis factor-alpha and matrix metalloproteinase expression. Circulation 98: 300–307; 1998.

    PubMed  CAS  Google Scholar 

  • Kol A. T.; Bourcier A. H.; Lichtman P.; Libby D. Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J. Clin. Invest. 103: 571–577; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Kuo C.; Campbell L. A. Detection of Chlamydia pneumoniae in arterial tissues. J. Infect. Dis. 181(Suppl 3): S432–436; 2000.

    Article  PubMed  CAS  Google Scholar 

  • Kuo C. C.; Gown A. M.; Benditt E. P.; Grayston J. T. Detection of Chlamydia pneumoniae in aortic lesions of atherosclerosis by immunocytochemical stain. Arterioscler. Thromb. 13: 1501–1504; 1993.

    Article  PubMed  CAS  Google Scholar 

  • LaVerda D.; Albanese L. N.; Ruther P. E.; Morrison S. G.; Morrison R. P.; Ault K. A.; Byrne G. I. Seroreactivity to Chlamydia trachomatis Hsp10 correlates with severity of human genital tract disease. Infect. Immun. 68: 303–309; 2000.

    Article  PubMed  CAS  Google Scholar 

  • LaVerda D.; Kalayoglu M. V.; Byrne G. I. Chlamydial heat shock proteins and disease pathology: new paradigms for old problems? Infect. Dis. Obstet. Gynecol. 7: 64–71; 1999.

    Article  PubMed  CAS  Google Scholar 

  • Miyashita N.; Ouchi K.; Kawasaki K.; Komura H.; Kawai Y.; Obase Y.; Kobashi Y.; Oka M. Evaluation of enzyme-linked immunosorbent assay for Chlamydophila pneumoniae-specific immunoglobulin M in acute respiratory tract infection. Respirology 13: 299–302; 2008.

    Article  PubMed  Google Scholar 

  • Moreno C.; Merino J.; Ramírez N.; Echeverría A.; Pastor F.; Sánchez-Ibarrola A. Lipopolysaccharide needs soluble CD14 to interact with TLR4 in human monocytes depleted of membrane CD14. Microbes. Infect. 6: 990–995; 2004.

    Article  PubMed  CAS  Google Scholar 

  • Netea M. G.; Kullberg B. J.; Jacobs L. E.; Verver-Jansen T. J.; van der Ven-Jongekrijg J.; Galama J. M.; Stalenhoef A. F.; Dinarello C. A.; Van der Meer J. W. Chlamydia pneumoniae stimulates IFN-gamma synthesis through MyD88-dependent, TLR2- and TLR4-independent induction of IL-18 release. J. Immunol. 173: 1477–1482; 2004.

    PubMed  CAS  Google Scholar 

  • Ragno S.; Winrow V. R.; Mascagni P.; Lucietto P.; Di Pierro F.; Morris C. J.; Blake D. R. Asynthetic 10-kD heat shock protein (hsp10) from Mycobacterium tuberculosis modulates adjuvant arthritis. Clin. Exp. Immunol. 103: 384–390; 1996.

    Article  PubMed  CAS  Google Scholar 

  • Rodriguez N.; Dietrich H.; Mossbrugger I.; Weintz G.; Scheller J.; Hammer M. Increased inflammation and impaired resistance to Chlamydophila pneumoniae infection in Dusp1(−/−) mice: critical role of IL-6. J. Leukoc. Biol. 88: 579–587; 2010.

    Article  PubMed  CAS  Google Scholar 

  • Romano C. C.; Nuzzo I.; Cozzolino D.; Bentivoglio C.; Paolillo R.; Rizzo A. Relationship between Chlamydia pneumoniae infection, inflammatory markers, and coronary heart diseases. Int. Immunopharmacol. 6: 848–853; 2006.

    Article  Google Scholar 

  • Prebeck S.; Kirschning C.; Dürr S.; da Costa C.; Donath B.; Brand K.; Redecke V.; Wagner H.; Miethke T. Predominant role of Toll-like receptor 2 versus 4 in Chlamydia pneumoniae-induced activation of dendritic cells. J. Immunol. 167: 3316–3323; 2001.

    PubMed  CAS  Google Scholar 

  • Sasu S.; LaVerda D.; Qureshi N.; Golenbock D. T.; Beasley D. Chlamydia pneumoniae and chlamydial heat shock protein 60 stimulate proliferation of human vascular smooth muscle cells via toll-like receptor 4 and p44/p42 mitogen-activated protein kinase activation. Circ. Res. 89: 244–250; 2001.

    Article  PubMed  CAS  Google Scholar 

  • Tiran A.; Gruber H. J.; Graier W. F.; Wagner A. H.; Van Leeuwen E. B.; Tiran B. Aspirin inhibits Chlamydia pneumoniae-induced nuclear factor-kappa B activation, cytokine expression, and bacterial development in human endothelial cells. Arterioscler. Thromb. Vasc. Biol. 22: 1075–1080; 2002.

    Article  PubMed  CAS  Google Scholar 

  • Törmäkangas L.; Markkula E.; Lounatmaa K.; Puolakkainen M.; Puolakkainen. Chlamydia pneumoniae infection in polarized epithelial cell lines. Infect. Immun. 78: 2714–2722; 2010.

    Article  PubMed  Google Scholar 

  • Yamamoto H.; Watanabe T.; Miyazaki A.; Katagiri T.; Idei T.; Iguchi T.; Mimura M.; Kamijima K. High prevalence of Chlamydia pneumoniae antibodies and increased high-sensitive C-reactive protein in patients with vascular dementia. J. Am. Geriatr. Soc. 53: 583–589; 2005.

    Article  PubMed  Google Scholar 

  • Yang J.; Hooper W. C.; Phillips D. J.; Tondella M. L.; Talkington D. F. Induction of proinflammatory cytokines in human lung epithelial cells during Chlamydia pneumoniae infection. Infect. Immun. 71: 614–620; 2003.

    Article  PubMed  CAS  Google Scholar 

  • Youn J. H.; Oh Y. J.; Kim E. S.; Choi J. E.; Shin J. S. High mobility group box 1 protein binding to lipopolysaccharide facilitates transfer of lipopolysaccharide to CD14 and enhances lipopolysaccharide-mediated TNF-alpha production in human monocytes. J. Immunol. 180: 5067–5074; 2008.

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

We thank the National Natural Science Foundation of China (no. 30901352), Innovative Research Team in University of Hunan province (number: [2008] 51), Hunan Provincial Innovation Foundation For Postgraduate, and Hunan Provincial training and innovation base for post-graduate, for their financial support of this study.

Author information

Authors and Affiliations

  1. Pathogenic Biology Institute, University of South China, No. 28 Changsheng Western Road, Hengyang, 421001, People’s Republic of China

    Z. Zhou, Y. Wu, L. Chen, L. Liu, H. Chen, Z. Li & C. Chen

Authors
  1. Z. Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L. Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Z. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Wu.

Additional information

Editor: T. Okamoto

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhou, Z., Wu, Y., Chen, L. et al. Heat shock protein 10 of Chlamydophila pneumoniae induces proinflammatory cytokines through Toll-like receptor (TLR) 2 and TLR4 in human monocytes THP-1. In Vitro Cell.Dev.Biol.-Animal 47, 541–549 (2011). https://doi.org/10.1007/s11626-011-9441-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11626-011-9441-4

Keywords

Search

Navigation