International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
권호 표지
DOI QR코드

DOI QR Code

Xylitol Mitigate Neutrophil Inflammatory Response Against Porphyromonas gingivalis Infection

  • Na, Hee Sam (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Song, YuRi (Department of Oral Microbiology, School of Dentistry, Pusan National University) ;
  • Choi, Yoon Hee (Department of Hematology-Oncology, Dongnam Institute of Radiological and Medical Sciences) ;
  • Chung, Jin (Department of Oral Microbiology, School of Dentistry, Pusan National University)
  • Received : 2018.08.20
  • Accepted : 2018.09.17
  • Published : 2018.09.30
Download PDF
⟨ Previous Next ⟩

Abstract

Periodontitis is generally a chronic disorder characterized by breakdown of tooth-supporting tissues, producing dentition loss. Porphyromonas gingivalis (P. gingivalis), a Gramnegative anaerobic rod, is one of the major pathogens associated with periodontitis. Neutrophils are first line defense cells in the oral cavity that play a significant role in inflammatory response. Xylitol is a known anti-caries agent and has anti-inflammatory effects. In this study, we conducted experiments to evaluate anti-inflammatory effects of xylitol on P. gingivalis infected neutrophils for possible usage in prevention and treatment of periodontal infections. P. gingivalis was intraperitoneally injected and peritoneal lavage was collected for cytokine determination. For in vitro study, neutrophils were collected from mouse peritoneal cells after zymosan injection or bone marrow cells. Neutrophils were stimulated with live P. gingivalis and ELISA was used to determine the effect of xylitol on P. gingivalis induced cytokine production. $IL-1{\beta}$, IL-6, $TNF-{\alpha}$ concentration and neutrophil population in the peritoneal lavage was increased in P. gingivalis-infected mouse. Peritoneal cells infected with live P. gingivalis revealed significantly increased production of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$ at multiplicity of infection of 10. Neutrophils from bone marrow and peritoneal lavage revealed increased production of $IL-1{\beta}$, IL-6 and $TNF-{\alpha}$. Xylitol significantly mitigated P. gingivalis induced cytokine production in neutrophils. Findings indicate that xylitol is an anti-inflammatory agent in neutrophils infected with live P. gingivalis, that suggests its use in periodontitis management.

Keywords

References

  1. Medzhitov R. Origin and physiological roles of inflammation. Nature. 2008;454:428-35. doi: 10.1038/nature07201.
  2. Socransky SS, Haffajee AD. The bacterial etiology of destructive periodontal disease: current concepts. J Periodontol. 1992;63:322-31. doi: 10.1902/jop.1992.63.4s.322.
  3. Byrne SJ, Dashper SG, Darby IB, Adams GG, Hoffmann B, Reynolds EC. Progression of chronic periodontitis can be predicted by the levels of Porphyromonas gingivalis and Treponema denticola in subgingival plaque. Oral Microbiol Immunol. 2009;24:469-77. doi: 10.1111/j.1399-302X.2009.00544.x.
  4. Chen GY, Nunez G. Sterile inflammation: sensing and reacting to damage. Nat Rev Immunol. 2010;10:826-37. doi: 10.1038/nri2873.
  5. Delima AJ, Van Dyke TE. Origin and function of the cellular components in gingival crevice fluid. Periodontol 2000. 2003;31:55-76. https://doi.org/10.1034/j.1600-0757.2003.03105.x
  6. Ryder MI. Comparison of neutrophil functions in aggressive and chronic periodontitis. Periodontol 2000. 2010;53:124-37. doi: 10.1111/j.1600-0757.2009.00327.x.
  7. Wang J, Arase H. Regulation of immune responses by neutrophils. Ann N Y Acad Sci. 2014;1319:66-81. doi: 10.1111/nyas.12445.
  8. Landzberg M, Doering H, Aboodi GM, Tenenbaum HC, Glogauer M. Quantifying oral inflammatory load: oral neutrophil counts in periodontal health and disease. J Periodontal Res. 2015;50:330-6. doi: 10.1111/jre.12211.
  9. Aboodi GM, Goldberg MB, Glogauer M. Refractory periodontitis population characterized by a hyperactive oral neutrophil phenotype. J Periodontol. 2011;82:726-33. doi: 10.1902/jop.2010.100508.
  10. Gabay C, Lamacchia C, Palmer G. IL-1 pathways in inflammation and human diseases. Nat Rev Rheumatol. 2010;6:232-41. doi: 10.1038/nrrheum.2010.4.
  11. Assuma R, Oates T, Cochran D, Amar S, Graves DT. IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. J Immunol. 1998;160: 403-9.
  12. Han SJ, Jeong SY, Nam YJ, Yang KH, Lim HS, Chung J. Xylitol inhibits inflammatory cytokine expression induced by lipopolysaccharide from Porphyromonas gingivalis. Clin Diagng Lab Immunol. 2005;12:1285-91. doi: 10.1128/cdli.12.11.1285-1291.2005.
  13. Lamont RJ, Jenkinson HF. Life below the gum line: pathogenic mechanisms of Porphyromonas gingivalis. Microbiol Mol Biol Rev. 1998;62:1244-63.
  14. Craig RG, Yip JK, So MK, Boylan RJ, Socransky SS, Haffajee AD. Relationship of destructive periodontal disease to the acute-phase response. J Periodontol. 2003;74:1007-16. doi: 10.1902/jop.2003.74.7.1007.
  15. Dinarello CA. Immunological and inflammatory functions of the interleukin-1 family. Annu Rev Immunol. 2009;27: 519-50. doi: 10.1146/annurev.immunol.021908.132612.
  16. Chervenick PA, Boggs DR, Marsh JC, Cartwright GE, Wintrobe MM. Quantitative studies of blood and bone marrow neutrophils in normal mice. Am J Physiol. 1968; 215:353-60. doi: 10.1152/ajplegacy.1968.215.2.353.
  17. Tecchio C, Micheletti A, Cassatella MA. Neutrophil-derived cytokines: facts beyond expression. Front Immunol. 2014; 5:508. doi: 10.3389/fimmu.2014.00508.
  18. Damgaard C, Kantarci A, Holmstrup P, Hasturk H, Nielsen CH, Van Dyke TE. Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-alpha, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1. J Periodontal Res. 2017;52:246-54. doi: 10.1111/jre.12388.
  19. Dewas C, Dang PM, Gougerot-Pocidalo MA, El-Benna J. TNF-alpha induces phosphorylation of p47(phox) in human neutrophils: partial phosphorylation of p47phox is a common event of priming of human neutrophils by TNF-alpha and granulocyte-macrophage colony-stimulating factor. J Immunol. 2003;171:4392-8. https://doi.org/10.4049/jimmunol.171.8.4392
  20. Fujishima S, Hoffman AR, Vu T, Kim KJ, Zheng H, Daniel D, Kim Y, Wallace EF, Larrick JW, Raffin TA. Regulation of neutrophil interleukin 8 gene expression and protein secretion by LPS, TNF-alpha, and IL-1 beta. J Cell Physiol. 1993;154:478-85. doi: 10.1002/jcp.1041540305.
  21. Ferrante A. Activation of neutrophils by interleukins-1 and -2 and tumor necrosis factors. Immunol Ser. 1992;57:417-36.
  22. Akira S, Hirano T, Taga T, Kishimoto T. Biology of multifunctional cytokines: IL 6 and related molecules (IL 1 and TNF). FASEB J. 1990;4:2860-7. https://doi.org/10.1096/fasebj.4.11.2199284
  23. Chung Y, Chang SH, Martinez GJ, Yang XO, Nurieva R, Kang HS, Ma L, Watowich SS, Jetten AM, Tian Q, Dong C. Critical regulation of early Th17 cell differentiation by interleukin-1 signaling. Immunity. 2009;30:576-87. doi: 10.1016/j.immuni.2009.02.007.
  24. Gallin JI. Human neutrophil heterogeneity exists, but is it meaningful? Blood. 1984;63:977-83.
  25. Nourshargh S, Marelli-Berg FM. Transmigration through venular walls: a key regulator of leukocyte phenotype and function. Trends Immunol. 2005;26:157-65. doi: 10.1016/ j.it.2005.01.006.
  26. Lynch H, Milgrom P. Xylitol and dental caries: an overview for clinicians. J Calif Dent Assoc. 2003;31:205-9.
  27. Park E, Na HS, Kim SM, Wallet S, Cha S, Chung J. Xylitol, an anticaries agent, exhibits potent inhibition of inflammatory responses in human THP-1-derived macrophages infected with Porphyromonas gingivalis. J Periodontol. 2014; 85:e212-23. doi: 10.1902/jop.2014.130455.