International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Fusobacterium nucleatum GroEL signaling via Toll-like receptor 4 in human microvascular endothelial cells

  • Lee, Hae-Ri (Korea Centers for Disease Centers for Disease Control and Prevention) ;
  • Choi, Bong-Kyu (Department of Oral Microbiology and Immunology, School of Dentistry, Seoul National University)
  • Received : 2012.08.31
  • Accepted : 2012.09.11
  • Published : 2012.09.30
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Abstract

The GroEL heat-shock protein from Fusobacterium nucleatum, a periodontopathogen, activates risk factors for atherosclerosis in human microvascular endothelial cells (HMEC-1) and ApoE-/- mice. In this study, we analyzed the signaling pathways by which F. nucleatum GroEL induces the proinflammatory factors in HMEC-1 cells known to be risk factors associated with the development of atherosclerosis and identified the cellular receptor used by GroEL. The MAPK and NF-${\kappa}B$ signaling pathways were found to be activated by GroEL to induce the expression of interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, and tissue factor (TF). These effects were inhibited by a TLR4 knockdown. Our results thus indicate that TLR4 is a key receptor that mediates the interaction of F. nucleatum GroEL with HMEC-1 cells and subsequently induces an inflammatory response via the MAPK and NF-${\kappa}B$ pathways.

Keywords

References

  1. Bak EJ, Kim JH, Lee DE, Park BH, Ryu JH, Cha JH, Jeon RO, Yoo YJ. Inhibitory effect of SPA0355, a thiourea analogue, on inflammation and alveolar bone loss in rats with ligature-induced periodontitis. Int J Oral Biol. 2012;37:63-68.
  2. Choi HJ, Cho HK, Soh YJ. Protective Effect of HP08-0106 on Ligature-induced Periodontitis in Rats. Int J Oral Biol. 2011; 36:187-194.
  3. Ayada K, Yokota K, Kobayashi K, Shoenfeld Y, Matsuura E, Oguma K. Chronic infections and atherosclerosis. Clin Rev Allergy Immunol. 2009;37:44-748.
  4. Wick G, Perschinka H, Millonig G. Atherosclerosis as an autoimmune disease: an update. Trends Immunol. 2001;22:665-669.
  5. Tabeta K, Yamazaki K, Hotokezaka H, Yoshie H, Hara K. Elevated humoral immune response to heat shock protein 60 (hsp60) family in periodontitis patients. Clin Exp Immunol. 2000;120:285-293.
  6. Kolenbrander PE, Palmer RJ Jr, Periasamy S, Jakubovics, NS. Oral multispecies biofilm development and the key role of cell-cell distance. Nat Rev Microbiol. 2010;8:471-480.
  7. Ford PJ, Gemmell E, Chan A, Carter CL, Walker PJ, Bird PS, West MJ, Cullinan MP, Seymour GJ. Inflammation, heat shock proteins and periodontal pathogens in atherosclerosis: an immunohistologic study. Oral Microbiol Immunol. 2006; 21:206-211.
  8. Lee HR, Jun HK, Kim HD, Lee SH, Choi BK. Fusobacterium nucleatum GroEL induces risk factors of atherosclerosis in human microvascular endothelial cells and ApoE-/- mice. Mol Oral Microbiol. 201227:109-123.
  9. Wang W, Deng M, Liu X, Ai W, Tang Q, Hu J. TLR4 activation induces nontolerant inflammatory response in endothelial cells. Inflammation. 2011;34:509-518.
  10. Kol A, Bourcier T, Lichtman AH, Libby P. Chlamydial and human heat shock protein 60s activate human vascular endothelium, smooth muscle cells, and macrophages. J Clin Invest. 1999103:571-577.
  11. Graham GM, Farrar MD, Cruse-Sawyer JE, Holland KT, Ingham E. Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. Br J Dermatol. 2004;150:421-428.
  12. Baranova IN, Vishnyakova TG, Bocharov AV, Leelahavanichkul A, Kurlander R, Chen Z, Souza AC, Yuen PS, Star RA, Csako G, Patterson AP, Eggerman TL. Class B scavenger receptor types I and II and CD36 mediatebacterial recognition and proinflammatory signaling induced by Escherichia coli, lipopolysaccharide, and cytosolic chaperonin 60. J Immunol. 2012188:1371-1380.
  13. Vabulas RM, Ahmad-Nejad P, da Costa C, Miethke T, Kirschning CJ, Häcker H, Wagner H. Endocytosed HSP60s use Toll-like receptor 2 (TLR2) and TLR4 to activate the toll/interleukin-1 receptor signaling pathway in innate immune cells. J Biol Chem. 2001;276:31332-31339.
  14. Argueta JG, Shiota S, Yamaguchi N, Masuhiro Y, Hanazawa S. Induction of Porphyromonas gingivalis GroEL signaling via binding to Toll-like receptors 2 and 4. Oral Microbiol Immunol. 2006;21:245-251.
  15. Faure E, Equils O, Sieling PA, Thomas L, Zhang FX, Kirschning CJ, Polentarutti N, Muzio M, Arditi M. Bacterial lipopolysaccharide activates NF-$\kappa$B 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. 2000275:11058-11063.
  16. Han SH, Kim JH, Martin M, Michalek SM, Nahm MH. Pneumococcal lipoteichoic acid (LTA) is not as potent as staphylococcal LTA in stimulating Toll-like receptor 2. Infect Immun. 200371:5541-5548.