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

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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.

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References

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • Beertsen, W., McCulloch, C.A., and Sodek, J. 1997. The periodontal ligament: a unique, multifunctional connective tissue. Periodontol. 2000 13, 20–40.

    Article  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Darongsuwan, T. and Pavasant, P. 2001. Collagen I upregulates osteopontin expression in cultured periodontal ligament fibroblasts. J. Dent. Res. 80, 1384–1384.

    Google Scholar 

  • Gillette, J.M. and Nielsen-Preiss, S.M. 2004. The role of annexin 2 in osteoblastic mineralization. J. Cell Sci. 117, 441–449.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • Olney, R.C. 2003. Regulation of bone mass by growth hormone. Med. Pediatr. Oncol. 41, 228–234.

    Article  PubMed  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

  • 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.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Life Science, Dongguk University-Seoul, Seoul, 100-715, Republic of Korea

    Taegun Seo & Seho Cha

  2. Department of Periodontology, Dental Research Institute, Seoul National University School of Dentistry, Seoul, 110-749, Republic of Korea

    Tae-Il Kim & Jeong-Soon Lee

  3. Department of Cell and Developmental Biology, Seoul National University School of Dentistry, Seoul, 110-749, Republic of Korea

    Kyung Mi Woo

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  1. Taegun Seo
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  2. Seho Cha
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  3. Tae-Il Kim
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  4. Jeong-Soon Lee
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  5. Kyung Mi Woo
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Correspondence to Tae-Il Kim.

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Seo, T., Cha, S., Kim, TI. et al. Porphyromonas gingivalis-derived lipopolysaccharide-mediated activation of MAPK signaling regulates inflammatory response and differentiation in human periodontal ligament fibroblasts. J Microbiol. 50, 311–319 (2012). https://doi.org/10.1007/s12275-012-2146-x

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