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Ursodeoxycholic Acid Inhibits Inflammatory Cytokine Expression in THP-1 Cells Infected with Aggregatibacter actinomycetemcomitans

  • Song, YuRi (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Kim, SeYeon (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Park, Mee Hee (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Na, Hee Sam (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Chung, Jin (Department of Oral Microbiology, School of Dentistry, Pusan National University)
  • Received : 2017.02.21
  • Accepted : 2017.03.10
  • Published : 2017.03.31

Abstract

Background: Periodontitis is an inflammatory disease characterized by the breakdown of tooth-supporting tissues, leading to tooth loss. Aggregatibacter actinomycetemcomitans are major etiologic bacterium causing aggressive periodontitis. Ursodeoxycholic acid (UDCA), a hydrophilic gall bladder acid, has been used as an effective drug for various diseases related to immunity. The aim of this study was to investigate the effect of UDCA on the inflammatory response induced by A. actinomycetemcomitans. Methods: A human acute monocytic leukemia cell line (THP-1) was differentiated to macrophage- like cells by treatment with phorbol 12-mystristate 13-acetate (PMA) and used for all experiments. The cytotoxic effect of UDCA was examined by MTT assay. THP-1 cells were pretreated with UDCA for 30 min before A. actinomycetemcomitans infection and the culture supernatant was analyzed for various cytokine production by ELISA. The effect of UDCA on bacterial growth was examined by measuring optical densities using a spectrophotometer. Results: UDCA showed no cytotoxic effect on THP-1 cells, up to $80{\mu}M$ Ed highlight: Please confirm technical meaning. UDCA pretreatment inhibited the A. actinomycetemcomitans-induced $IL-1{\beta}$, $TNF-{\alpha}$, and IL-17A secretion in a dose-dependent manner. UDCA also inhibited IL-21 production at $60{\mu}M$. The production of IL-12 and IL-4 was not influenced by A. actinomycetemcomitans infection. Conclusion: These findings indicate that UDCA inhibits the production of inflammatory cytokines involved in innate and Th17 immune responses in A. actinomycetemcomitans-infected THP-1- derived macrophages, which suggests its possible use for the control of aggressive periodontitis.

Keywords

References

  1. Prakasam, A., S.S. Elavarasu, and R.K. Natarajan, Antibiotics in the management of aggressive periodontitis. J Pharm Bioallied Sci, 2012;4:S252-5 doi:http://dx.doi.org/10.1902/jop.2005.76.2.289.
  2. Gajardo, M., et al., Prevalence of periodontopathic bacteria in aggressive periodontitis patients in a Chilean population. J Periodontol, 2005;76(2):289-94 doi:http://dx.doi.org/ 10.1902/jop.2005.76.2.289.
  3. Slots, J. and M. Ting, Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in human periodontal disease: occurrence and treatment. Periodontol 2000, 1999;20:82-121. https://doi.org/10.1111/j.1600-0757.1999.tb00159.x
  4. Johansson, A., Aggregatibacter actinomycetemcomitans leukotoxin: a powerful tool with capacity to cause imbalance in the host inflammatory response. Toxins (Basel), 2011;3(3): 242-59. doi:http://dx.doi.org/10.3390/toxins3030242.
  5. Gursoy, U.K., Periodontal bacteria and epithelial cell interactions: role of bacterial proteins. Eur J Dent, 2008;2(4):231-2.
  6. Tribble, G.D. and R.J. Lamont, Bacterial invasion of epithelial cells and spreading in periodontal tissue. Periodontol 2000, 2010;52(1):68-83. https://doi.org/10.1111/j.1600-0757.2009.00323.x
  7. Park, E., et al., Activation of NLRP3 and AIM2 inflammasomes by Porphyromonas gingivalis infection. Infect Immun, 2014;82(1):112-23. https://doi.org/10.1128/IAI.00862-13
  8. Li, Y., et al., D(-)-Salicin inhibits the LPS-induced inflammation in RAW264.7 cells and mouse models. Int Immunopharmacol, 2015;26(2):286-94. doi:http://dx.doi.org/10.1016/j.intimp.2015.04.016
  9. Joo, S.S., et al., Ursodeoxycholic acid inhibits pro-inflammatory repertoires, IL-1 beta and nitric oxide in rat microglia. Arch Pharm Res, 2006;26(12):1067-73. https://doi.org/10.1007/BF02994760
  10. Tint, G.S., et al., Ursodeoxycholic acid: a safe and effective agent for dissolving cholesterol gallstones. Ann Intern Med, 1982;97(3):351-6. https://doi.org/10.7326/0003-4819-97-3-351
  11. Hajishengallis, G., Immune evasion strategies of Porphyromonas gingivalis. J Oral Biosci, 2011;53(3)233-240.
  12. Kononen, E. and H.P. Muller, Microbiology of aggressive periodontitis. Periodontol 2000, 2014;65(1):46-78. https://doi.org/10.1111/prd.12016
  13. Kelk, P., et al., Abundant secretion of bioactive interleukin-1beta by human macrophages induced by Actinobacillus actinomycetemcomitans leukotoxin. Infect Immun, 2005;73(1):453-8. https://doi.org/10.1128/IAI.73.1.453-458.2005
  14. Shenker, B.J., et al., Aggregatibacter actinomycetemcomitans cytolethal distending toxin activates the NLRP3 inflammasome in human macrophages, leading to the release of proinflammatory cytokines. Infect Immun, 2015;83(4): 1487-96. doi:http://dx.doi.org/ 10.1128/IAI.03132-14.
  15. Cekici, A., et al., Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000, 2014;64(1):57-80. doi:http://dx.doi.org/10.1111/prd.12002.
  16. Nguyen, L., et al., Interleukin-1 beta stimulates bone resorption and inhibits bone formation in vivo. Lymphokine Cytokine Res, 1991;10(1-2):15-21.
  17. Arun, K.V., A. Talwar, and T.S. Kumar, T-helper cells in the etiopathogenesis of periodontal disease: A mini review. J Indian Soc Periodontol, 2011;15(1):4-10. doi:http://dx.doi.org/10.4103/0972-124x.82255
  18. Zacarias, J.M., et al., The Influence of Interleukin 17A and IL17F Polymorphisms on Chronic Periodontitis Disease in Brazilian Patients. Mediators Inflamm, 2015;2015:147056.
  19. Takahashi, K., et al., The potential role of interleukin-17 in the immunopathology of periodontal disease. J Clin Periodontol, 2005;32(4):369-74. https://doi.org/10.1111/j.1600-051X.2005.00676.x
  20. Dutzan, N., et al., Interleukin-21 expression and its association with proinflammatory cytokines in untreated chronic periodontitis patients. J Periodontol, 2012;83(7):948-54. https://doi.org/10.1902/jop.2011.110482
  21. Park, S.-H., A Short-Term Study of the Effects of UDCA on Gingival Inflammation in the Beagle Dog. J Korean Acad Periodontol, 1999;1-14.
  22. Sombetzki, M., et al., 24-nor-ursodeoxycholic acid ameliorates inflammatory response and liver fibrosis in a murine model of hepatic schistosomiasis. J Hepatol, 2015; 62(4):871-8. doi: http://dx.doi.org/10.1016/j.jhep.2014.11.020.
  23. Pang, L., et al., Anticancer Effect of Ursodeoxycholic Acid in Human Oral Squamous Carcinoma HSC-3 Cells through the Caspases. Nutrients, 2015;7(5):3200-18. doi:http://dx.doi.org/10.3390/nu7053200.