International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
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Mechanisms Underlying Enterococcus faecalis-Induced Tumor Necrosis Factor-$\alpha$ Production in Macrophages

  • Choi, Eun-Kyoung (Department of Oral Microbiology, Dental Science Research Institute, Chonnam National University Dental School) ;
  • Kim, Dae-Eob (Department of Conservative Dentistry, Dental Science Research Institute, Chonnam National University Dental School) ;
  • Oh, Won-Mann (Department of Conservative Dentistry, Dental Science Research Institute, Chonnam National University Dental School) ;
  • Paek, Yun-Woong (Department of Physical Therapy, Gwangju Health College University) ;
  • Kang, In-Chol (Department of Oral Microbiology, Dental Science Research Institute, Chonnam National University Dental School)
  • Received : 2010.04.09
  • Accepted : 2010.06.04
  • Published : 2010.06.30
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Abstract

Enterococcus faecalis, a gram-positive bacterium, has been implicated in endodontic infections, particularly in chronic apical periodontitis. Proinflammatory cytokines, including tumor necrosis factor-$\alpha$ (TNF-$\alpha$), are involved in the pathogenesis of these apical lesions. E. faecalis has been reported to stimulate macrophages to produce TNF-$\alpha$. The present study investigated the mechanisms involved in TNF-$\alpha$ production by a murine macrophage cell line, RAW 264.7 in response to exposure to E. faecalis. Both live and heat-killed E. faecalis induced high levels of gene expression and protein release of TNF-$\alpha$. Treatment of RAW 264.7 cells with cytochalasin D, an inhibitor of endocytosis, prevented the mRNA up-regulation of TNF-$\alpha$ by E. faecalis. In addition, antioxidant treatment reduced TNF-$\alpha$ production to baseline levels. Inhibition of extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein (MAP) kinase also significantly attenuated E. faecalis-induced TNF-$\alpha$ expression by RAW 264.7 cells. Furthermore, activation of NF-${\kappa}B$ and AP-1 in RAW 264.7 cells was also stimulated by E. faecalis. These results suggest that the phagocytic uptake of bacteria is necessary for the induction of TNF-$\alpha$ in E. faecalis-stimulated macrophages, and that the underlying intracellular signaling pathways involve reactive oxygen species, ERK, p38 MAP kinase, NF-${\kappa}B$, and AP-1.

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References

  1. Baeuerle PA, Henkel T. Function and activation of NF-$\kappa$B in the immune system. Annu Rev Immunol. 1994;12:141-179. https://doi.org/10.1146/annurev.iy.12.040194.001041
  2. Baik JE, Kum KY, Yun CH, Lee JK, Lee K, Kim KK, Han SH. Calcium hydroxide inactivates lipoteichoic acid from Enterococcus faecalis. J Endod. 2008;34:1355-1359. https://doi.org/10.1016/j.joen.2008.08.014
  3. Baik JE, Ryu YH, Han JY, Im J, Kum KY, Yun CH, Lee K, Han SH. Lipoteichoic acid partially contributes to the inflammatory responses to Enterococcus faecalis. J Endod. 2008;34:975-982. https://doi.org/10.1016/j.joen.2008.05.005
  4. Danin J, Linder LE, Lundqvist G, Andersson L. Tumor necrosis factor-$\alpha$and transforming growth factor-$\alpha$in chronic periapical lesions. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2000;90:514-517. https://doi.org/10.1067/moe.2000.108958
  5. Forman HJ, Torres M, Fukuto J. Redox signaling. Mol Cell Biochem. 2002;234-235:49-62.
  6. Hancock HH 3rd, Sigurdsson A, Trope M, Moiseiwitsch J. Bacteria isolated after unsuccessful endodontic treatment in a North American population. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2001;91:579-586. https://doi.org/10.1067/moe.2001.113587
  7. Kim JY, Jeong D, Roh S, Min BM. Changes in mitogenactivated protein kinase activities during acidification-induced apoptosis in CHO cells. Int J Oral Biol. 2005;30;85-90.
  8. Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 1997;9:180-186. https://doi.org/10.1016/S0955-0674(97)80061-0
  9. Stashenko P, Teles R, D'Souza R. Periapical inflammatory responses and their modulation. Crit Rev Oral Biol Med. 1998;9:498-521. https://doi.org/10.1177/10454411980090040701
  10. Stuart CH, Schwartz SA, Beeson TJ, Owatz CB. Enterococcus faecalis: its role in root canal treatment failure and current concepts in retreatment. J Endod. 2006;32:93-98.
  11. Sunde PT, Olsen I, Debelian GJ, Tronstad L. Microbiota of periapical lesions refractory to endodontic therapy. J Endod. 2002;28:304-310. https://doi.org/10.1097/00004770-200204000-00011