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Mechanisms of tissue factor induction by Porphyromonas gingivalis in human endothelial cells

  • Kim, So-Hee (Dental Science Research Institute, Chonnam National University) ;
  • Jung, Ji-Yeon (Dental Science Research Institute, Chonnam National University) ;
  • Kim, Won-Jae (Dental Science Research Institute, Chonnam National University) ;
  • Kim, Ok-Joon (Dental Science Research Institute, Chonnam National University) ;
  • Kim, Young (Dental Science Research Institute, Chonnam National University) ;
  • Kang, In-Chol (Dental Science Research Institute, Chonnam National University)
  • Received : 2021.06.26
  • Accepted : 2021.08.24
  • Published : 2021.09.30

Abstract

Associations between periodontal infection and cardiovascular disease have been documented. Porphyromonas gingivalis is a well-established periodontal pathogen, and tissue factor (TF) is a key initiator of the coagulation cascade. In this context, P. gingivalis has been reported to enhance TF expression in human endothelial cells. The present study investigated the underlying mechanisms of TF induction by P. gingivalis in human umbilical vein endothelial cells. P. gingivalis increased TF expression in a dose- and time-dependent manner. Not only live bacteria but also glutaraldehyde-fixed bacteria increased TF expression to the same extent. However, sonicates of P. gingivalis did not induce TF expression. Cytochalasin D and SMIFH2, which are inhibitors of actin polymerization and actin nucleation, respectively, inhibited the TF expression induced by P. gingivalis. Finally, TF production was decreased or increased in the presence of various signaling inhibitors, including mitogen-activated protein kinases. These results suggest that P. gingivalis induces endothelial TF expression by a bacterial internalization-dependent mechanism and through diverse signal transduction mechanisms.

Keywords

Acknowledgement

This study was financially supported by Chonnam National University (Grant number: 2018-3478).

References

  1. Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers 2017;3:17038. doi: 10.1038/nrdp.2017.38.
  2. Kononen E, Gursoy M, Gursoy UK. Periodontitis: a multifaceted disease of tooth-supporting tissues. J Clin Med 2019;8:1135. doi: 10.3390/jcm8081135.
  3. Bui FQ, Almeida-da-Silva CLC, Huynh B, Trinh A, Liu J, Woodward J, Asadi H, Ojcius DM. Association between periodontal pathogens and systemic disease. Biomed J 2019;42:27-35. doi: 10.1016/j.bj.2018.12.001.
  4. Hasturk H, Kantarci A. Activation and resolution of periodontal inflammation and its systemic impact. Periodontol 2000 2015;69:255-73. doi: 10.1111/prd.12105.
  5. Mulhall H, Huck O, Amar S. Porphyromonas gingivalis, a long-range pathogen: systemic impact and therapeutic implications. Microorganisms 2020;8:869. doi: 10.3390/microorganisms8060869.
  6. Xu W, Zhou W, Wang H, Liang S. Roles of Porphyromonas gingivalis and its virulence factors in periodontitis. Adv Protein Chem Struct Biol 2020;120:45-84. doi: 10.1016/bs.apcsb.2019.12.001.
  7. Haraszthy VI, Zambon JJ, Trevisan M, Zeid M, Genco RJ. Identification of periodontal pathogens in atheromatous plaques. J Periodontol 2000;71:1554-60. doi: 10.1902/jop.2000.71.10.1554.
  8. Kozarov EV, Dorn BR, Shelburne CE, Dunn WA Jr, Progulske-Fox A. Human atherosclerotic plaque contains viable invasive Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. Arterioscler Thromb Vasc Biol 2005;25:e17-8. doi: 10.1161/01.ATV.0000155018.67835.1a.
  9. Olsen I, Progulske-Fox A. Invasion of Porphyromonas gingivalis strains into vascular cells and tissue. J Oral Microbiol 2015;7:28788. doi: 10.3402/jom.v7.28788.
  10. Lalla E, Lamster IB, Hofmann MA, Bucciarelli L, Jerud AP, Tucker S, Lu Y, Papapanou PN, Schmidt AM. Oral infection with a periodontal pathogen accelerates early atherosclerosis in apolipoprotein E-null mice. Arterioscler Thromb Vasc Biol 2003;23:1405-11. doi: 10.1161/01.ATV.0000082462.26258.FE.
  11. Pussinen PJ, Mattila K. Periodontal infections and atherosclerosis: mere associations? Curr Opin Lipidol 2004;15:583-8. doi: 10.1097/00041433-200410000-00013.
  12. Grover SP, Mackman N. Tissue factor: an essential mediator of hemostasis and trigger of thrombosis. Arterioscler Thromb Vasc Biol 2018;38:709-25. doi: 10.1161/ATVBAHA.117.309846.
  13. Steffel J, Luscher TF, Tanner FC. Tissue factor in cardiovas-cular diseases: molecular mechanisms and clinical implications. Circulation 2006;113:722-31. doi: 10.1161/CIRCULATIONAHA.105.567297.
  14. Witkowski M, Landmesser U, Rauch U. Tissue factor as a link between inflammation and coagulation. Trends Cardiovasc Med 2016;26:297-303. doi: 10.1016/j.tcm.2015.12.001.
  15. Roth GA, Aumayr K, Giacona MB, Papapanou PN, Schmidt AM, Lalla E. Porphyromonas gingivalis infection and prothrombotic effects in human aortic smooth muscle cells. Thromb Res 2009;123:780-4. doi: 10.1016/j.thromres.2008.07.008.
  16. Roth GA, Moser B, Huang SJ, Brandt JS, Huang Y, Papapanou PN, Schmidt AM, Lalla E. Infection with a periodontal pathogen induces procoagulant effects in human aortic endothelial cells. J Thromb Haemost 2006;4:2256-61. doi: 10.1111/j.1538-7836.2006.02128.x.
  17. Gavrilin MA, Bouakl IJ, Knatz NL, Duncan MD, Hall MW, Gunn JS, Wewers MD. Internalization and phagosome escape required for Francisella to induce human monocyte IL-1beta processing and release. Proc Natl Acad Sci U S A 2006;103:141-6. doi: 10.1073/pnas.0504271103.
  18. Kang IC, Kuramitsu HK. Induction of monocyte chemoattractant protein-1 by Porphyromonas gingivalis in human endothelial cells. FEMS Immunol Med Microbiol 2002;34:311-7. doi: 10.1111/j.1574-695X.2002.tb00639.x.
  19. Shin OS, Isberg RR, Akira S, Uematsu S, Behera AK, Hu LT. Distinct roles for MyD88 and Toll-like receptors 2, 5, and 9 in phagocytosis of Borrelia burgdorferi and cytokine induction. Infect Immun 2008;76:2341-51. doi: 10.1128/IAI.01600-07.
  20. Markowicz C, Kubiak P, Grajek W, Schmidt MT. Inactivation of Lactobacillus rhamnosus GG by fixation modifies its probiotic properties. Can J Microbiol 2016;62:72-82. doi: 10.1139/cjm2015-0249.
  21. Barkman C, Martner A, Hessle C, Wold AE. Soluble bacterial constituents down-regulate secretion of IL-12 in response to intact Gram-positive bacteria. Microbes Infect 2008;10:1484-93. doi: 10.1016/j.micinf.2008.08.011.
  22. Jagger MP, Huo Z, Riches PG. Inflammatory cytokine (interleukin 6 and tumour necrosis factor alpha) release in a human whole blood system in response to Streptococcus pneumoniae serotype 14 and its capsular polysaccharide. Clin Exp Immunol 2002;130:467-74. https://doi.org/10.1046/j.1365-2249.2002.01946.x
  23. Amar S, Wu SC, Madan M. Is Porphyromonas gingivalis cell invasion required for atherogenesis? Pharmacotherapeutic implications. J Immunol 2009;182:1584-92. doi: 10.4049/jimmunol.182.3.1584.
  24. Choi EK, Park SA, Oh WM, Kang HC, Kuramitsu HK, Kim BG, Kang IC. Mechanisms of Porphyromonas gingivalis-induced monocyte chemoattractant protein-1 expression in endothelial cells. FEMS Immunol Med Microbiol 2005;44:51-8. doi: 10.1016/j.femsim.2004.12.003.
  25. Rengarajan M, Hayer A, Theriot JA. Endothelial cells use a formin-dependent phagocytosis-like process to internalize the bacterium Listeria monocytogenes. PLoS Pathog 2016;12:e1005603. doi: 10.1371/journal.ppat.1005603.