The Journal of Microbiology

, Volume 50, Issue 2, pp 311–319

Porphyromonas gingivalis-derived lipopolysaccharide-mediated activation of MAPK signaling regulates inflammatory response and differentiation in human periodontal ligament fibroblasts

  • Taegun Seo
  • Seho Cha
  • Tae-Il Kim
  • Jeong-Soon Lee
  • Kyung Mi Woo
Articles

Abstract

Porphyromonas gingivalis (P.g.), which is a potential pathogen for periodontal diseases, contains lipopolysaccharide (LPS), and this endotoxin stimulates a variety of cellular responses. At present, P.g.-derived LPS-induced cellular responses in human periodontal ligament fibroblasts (PDLFs) are not well characterized. Here, we demonstrate that P.g-derived LPS regulates inflammatory responses, apoptosis and differentiation in PDLFs. Interleukin-6 (IL-6) and -8 (IL-8) were effectively upregulated by treatment of P.g.-derived LPS, and we confirmed apoptosis markers including elevated cytochrome c levels, active caspase-3 and morphological change in the presence of P.g.-derived LPS. Moreover, when PDLFs were cultured with differentiation media, P.g.-derived LPS reduced the expression of differentiation marker genes, as well as reducing alkaline phosphatase (ALP) activity and mineralization. P.g.-derived LPS-mediated these cellular responses were effectively abolished by treatment of mitogen-activated protein kinase (MAPK) inhibitors. Taken together, our results suggest that P.g.-derived LPS regulates several cellular responses via activation of MAPK signaling pathways in PDLFs.

Keywords

apoptosis cell differentiation lipopolysaccharide mitogen-activated protein kinase periodontal ligament Porphyromonas gingivalis 

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References

  1. Aly, H.A.A., Lightfoot, D.A., and El-Shemy, H.A. 2010. Bacterial lipopolysaccharide-induced oxidative stress in adult rat Sertoli cells in vitro. Toxicol. In Vitro 24, 1266–1272.PubMedCrossRefGoogle Scholar
  2. Angrisano, T., Pero, R., Peluso, S., Keller, S., Sacchetti, S., Bruni, C.B., Chiariotti, L., and Lembo, F. 2010. LPS-induced IL-8 activation in human intestinal epithelial cells is accompanied by specific histone H3 acetylation and methylation changes. BMC Microbiol. 10, 172.PubMedCrossRefGoogle Scholar
  3. Basdra, E.K. and Komposch, G. 1997. Osteoblast-like properties of human periodontal ligament cells: an in vitro analysis. Eur. J. Orthodont. 19, 615–621.CrossRefGoogle Scholar
  4. Beertsen, W., McCulloch, C.A., and Sodek, J. 1997. The periodontal ligament: a unique, multifunctional connective tissue. Periodontol. 2000 13, 20–40.CrossRefGoogle Scholar
  5. Bullon, P., Cordero, M.D., Quiles, J.L., Morillo, J.M., Ramirez-Tortosa, M.D., and Battino, M. 2011. Mitochondrial dysfunction promoted by Porphyromonas gingivalislipopolysaccharide as a possible link between cardiovascular disease and periodontitis. Free Radic. Biol. Med. 50, 1336–1343.PubMedCrossRefGoogle Scholar
  6. Darongsuwan, T. and Pavasant, P. 2001. Collagen I upregulates osteopontin expression in cultured periodontal ligament fibroblasts. J. Dent. Res. 80, 1384–1384.Google Scholar
  7. Gillette, J.M. and Nielsen-Preiss, S.M. 2004. The role of annexin 2 in osteoblastic mineralization. J. Cell Sci. 117, 441–449.PubMedCrossRefGoogle Scholar
  8. Gorina, R., Font-Nieves, M., Marquez-Kisinousky, L., Santalucia, T., and Planas, A.M. 2011. Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NFkappaB signaling, MAPK, and Jak1/Stat1 pathways. Glia 59, 242–255.PubMedCrossRefGoogle Scholar
  9. Gutierrez-Venegas, G., Kawasaki-Cardenas, P., Cruz-Arroyo, S.R., Perez-Garzon, M., and Maldonado-Frias, S. 2006. Actinobacillus actinomycetemcomitans lipopolysaccharide stimulates the phosphorylation of p44 and p42 MAP kinases through CD14 and TLR-4 receptor activation in human gingival fibroblasts. Life Sci. 78, 2577–2583.PubMedCrossRefGoogle Scholar
  10. Hagewald, S., Zimmermann, B., Mertens, P., and Bernimoulin, J.P. 1998. In vitro mineralization of human periodontal ligament cells. J. Dent. Res. 77, 1248–1248.Google Scholar
  11. Hashizume, T., Kurita-Ochiai, T., and Yamamoto, M. 2011. Porphyromonas gingivalis stimulates monocyte adhesion to human umbilical vein endothelial cells. FEMS Immunol. Med. Microbiol. 62, 57–65.PubMedCrossRefGoogle Scholar
  12. Isaka, J., Ohazama, A., Kobayashi, M., Nagashima, C., Takiguchi, T., Kawasaki, H., Tachikawa, T., and Hasegawa, K. 2001. Participation of periodontal ligament cells with regeneration of alveolar bone. J. Periodontol. 72, 314–323.PubMedCrossRefGoogle Scholar
  13. Kadono, H., Kido, J., Kataoka, M., Yamauchi, N., and Nagata, T. 1999. Inhibition of osteoblastic cell differentiation by lipopolysaccharide extract from Porphyromonas gingivalis. Infect. Immun. 67, 2841–2846.PubMedGoogle Scholar
  14. Kasamatsu, A., Uzawa, K., Shimada, K., Shiiba, M., Otsuka, Y., Seki, N., Abiko, Y., and Tanzawa, H. 2005. Elevation of galectin-9 as an inflammatory response in the periodontal ligament cells exposed to Porphylomonas gingivalis lipopolysaccharide in vitro and in vivo. Int. J. Biochem. Cell. B 37, 397–408.CrossRefGoogle Scholar
  15. Kawase, T., Sato, S., Miake, K., and Saito, S. 1988. Alkaline phosphatase of human periodontal ligament fibroblast-like cells. Adv. Dent. Res. 2, 234–239.PubMedGoogle Scholar
  16. Krajewski, A.C., Biessei, J., Kunze, M., Maersch, S., Perabo, L., and Noack, M.J. 2009. Influence of lipopolysaccharide and interleukin-6 on RANKL and OPG expression and release in human periodontal ligament cells. APMIS 117, 746–754.PubMedCrossRefGoogle Scholar
  17. Lee, Y.S., Bak, E.J., Kim, M.Y., Park, W., Seo, J.T., and Yoo, Y.J. 2008. Induction of IL-8 in periodontal ligament cells by H2O2. J. Microbiol. 46, 579–584.PubMedCrossRefGoogle Scholar
  18. Lee, S.K., Choi, H.I., Yang, Y.S., Jeong, G.S., Hwang, J.H., Lee, S.I., Kang, K.H., Cho, J.H., Chae, J.M., Lee, S.K., Kim, Y.C., and Kim, E.C. 2009. Nitric oxide modulates osteoblastic differentiation with heme oxygenase-1 via the mitogen activated protein kinase and nuclear factor-kappaB pathways in human periodontal ligament cells. Biol. Pharm. Bull. 32, 1328–1334.PubMedCrossRefGoogle Scholar
  19. Liew, C.Y., Lam, K.W., Kim, M.K., Harith, H.H., Tham, C.L., Cheah, Y.K., Sulaiman, M.R., Lajis, N.H., and Israf, D.A. 2011. Effects of 3-(2-Hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone (HMP) upon signalling pathways of lipopolysaccharide-induced iNOS synthesis in RAW 264.7 cells. Int. Immunopharmacol. 11, 85–95.PubMedCrossRefGoogle Scholar
  20. Manolagas, S.C. 2000. Birth and death of bone cells: basic regulatory mechanisms and implications for the pathogenesis and treatment of osteoporosis. Endocr. Rev. 21, 115–137.PubMedCrossRefGoogle Scholar
  21. Munshi, N., Fernandis, A.Z., Cherla, R.P., Park, I.W., and Ganju, R.K. 2002. Lipopolysaccharide-induced apoptosis of endothelial cells and its inhibition by vascular endothelial growth factor. J. Immunol. 168, 5860–5866.PubMedGoogle Scholar
  22. Nociti, F.H.Jr., Foster, B.L., Barros, S.P., Darveau, R.P., and Somerman, M.J. 2004. Cementoblast gene expression is regulated by Porphyromonas gingivalis lipopolysaccharide partially via toll-like receptor-4/MD-2. J. Dent. Res. 83, 602–607.PubMedCrossRefGoogle Scholar
  23. Olney, R.C. 2003. Regulation of bone mass by growth hormone. Med. Pediatr. Oncol. 41, 228–234.PubMedCrossRefGoogle Scholar
  24. Patil, C., Rossa, C., and Kirkwood, K.L. 2006. Actinobacillus actinomycetemcomitans lipopolysaccharide induces interleukin-6 expression through multiple mitogen-activated protein kinase pathways in periodontal ligament fibroblasts. Oral Microbiol. Immunol. 21, 392–398.PubMedCrossRefGoogle Scholar
  25. Rossa, C.Jr., Liu, M., and Kirkwood, K.L. 2008. A dominant function of p38 mitogen-activated protein kinase signaling in receptor activator of nuclear factor-kappaB ligand expression and osteoclastogenesis induction by Aggregatibacter actinomycetemcomitans and Escherichia coli lipopolysaccharide. J. Periodontal Res. 43, 201–211.PubMedCrossRefGoogle Scholar
  26. Seo, T., Cha, S., Woo, K.M., Park, Y.S., Cho, Y.M., Lee, J.S., and Kim, T.I. 2011. Synergic induction of human periodontal ligament fibroblast cell death by nitric oxide and N-methyl-D-aspartic acid receptor antagonist. J. Periodontal Implant Sci. 41, 17–22.PubMedCrossRefGoogle Scholar
  27. Seo, B.M., Miura, M., Gronthos, S., Bartold, P.M., Batouli, S., Brahim, J., Young, M., Robey, P.G., Wang, C.Y., and Shi, S.T. 2004. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364, 149–155.PubMedCrossRefGoogle Scholar
  28. Sun, W.B., Chu, C.L., Wang, J., and Zhao, H.T. 2007. Comparison of periodontal ligament cells responses to dense and nanophase hydroxyapatite. J. Mater Sci. Mater Med. 18, 677–683.PubMedCrossRefGoogle Scholar
  29. Suzuki, T., Kobayashi, M., Isatsu, K., Nishihara, T., Aiuchi, T., Nakaya, K., and Hasegawa, K. 2004. Mechanisms involved in apoptosis of human macrophages induced by lipopolysaccharide from Actinobacillus actinomycetemcomitans in the presence of cycloheximide. Infect. Immun. 72, 1856–1865.PubMedCrossRefGoogle Scholar
  30. Wada, N., Maeda, H., Yoshimine, Y., and Akamine, A. 2004. Lipopolysaccharide stimulates expression of osteoprotegerin and receptor activator of NF-kappa B ligand in periodontal ligament fibroblasts through the induction of interleukin-1 beta and tumor necrosis factor-alpha. Bone 35, 629–635.PubMedCrossRefGoogle Scholar
  31. Wang, M.J., Huang, H.Y., Chen, W.F., Chang, H.F., and Kuo, J.S. 2010. Glycogen synthase kinase-3 beta inactivation inhibits tumor necrosis factor-alpha production in microglia by modulating nuclear factor kappa B and MLK3/JNK signaling cascades. J. Neuroinflamm. 7, 99.CrossRefGoogle Scholar
  32. Yamamoto, T., Kita, M., Oseko, F., Nakamura, T., Imanishi, J., and Kanamura, N. 2006. Cytokine production in human periodontal ligament cells stimulated with Porphyromonas gingivalis. J. Periodontal Res. 41, 554–559.PubMedCrossRefGoogle Scholar
  33. Yang, H., Zhu, Y.T., Cheng, R., Shao, M.Y., Fu, Z.S., Cheng, L., Wang, F.M., and Hu, T. 2010. Lipopolysaccharide-induced dental pulp cell apoptosis and the expression of Bax and Bcl-2 in vitro. Braz. J. Med. Biol. Res. 43, 1027–1033.PubMedCrossRefGoogle Scholar
  34. Yu, J.H., Lee, S.P., Kim, T.I., and Jang, J.H. 2009. Identification of N-methyl-D-aspartate receptor subunit in human periodontal ligament fibroblasts: Potential role in regulating differentiation. J. Periodontol. 80, 338–346.PubMedCrossRefGoogle Scholar

Copyright information

© The Microbiological Society of Korea and Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Taegun Seo
    • 1
  • Seho Cha
    • 1
  • Tae-Il Kim
    • 2
  • Jeong-Soon Lee
    • 2
  • Kyung Mi Woo
    • 3
  1. 1.Department of Life ScienceDongguk University-SeoulSeoulRepublic of Korea
  2. 2.Department of Periodontology, Dental Research InstituteSeoul National University School of DentistrySeoulRepublic of Korea
  3. 3.Department of Cell and Developmental BiologySeoul National University School of DentistrySeoulRepublic of Korea

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