Intragingival injection of Porphyromonas gingivalis-derived lipopolysaccharide induces a transient increase in gingival tumour necrosis factor-α, but not interleukin-6, in anaesthetised rats

Abstract

A rat model offers insights into the bacterially-induced inflammatory response that contributes to the tissue damage in periodontal disease. Several studies have demonstrated that lipopolysaccharide (LPS), a component of the bacterial cell wall, can promote tissue damage in the gums. However, these experiments typically used LPS from bacteria not associated with periodontal disease. Researchers led by Tadashi Saigusa from Nihon University School of Dentistry in Matsudo, Japan, studied the effect of LPS from Porphyromonoas gingivalis, which is linked to periodontal disease, on rats. They identified a specific inflammatory signal that was activated by P.gingivalis, but not by LPS from another bacterial species that typically resides in the gut. These data highlight the importance of using appropriate bacterial species to model periodontal disease, and reveal molecular pathways that might contribute to this pathology.

Keywords

Porphyromonas gingivalis / lipopolysaccharide / gingiva / tumour necrosis factor-α / microdialysis

References

[1] Page RC. The role of inflammatory mediators in the pathogenesis of periodontal disease. J Periodontal Res, 1991, 26: 230-242.

[2] Slots J. Periodontology: past, present, perspectives. Periodontol 2000, 2013, 62(1): 7-19.

[3] Wilson M. Biological activities of lipopolysaccharides from oral bacteria and their relevance to the pathogenesis of chronic periodontitis. Sci Prog, 1995, 78: 19-34.

[4] Nakai K, Kawato T, Morita T. Angiotensin II induces the production of MMP-3 and MMP-13 through the MAPK signaling pathways via the AT(1) receptor in osteoblasts. Biochimie, 2013, 95(4): 922-933.

[5] de Aquino SG, Guimaraes MR, Stach-Machado DR. Differential regulation of MMP-13 expression in two models of experimentally induced periodontal disease in rats. Arch Oral Biol, 2009, 54(7): 609-617.

[6] Dumitrescu AL, Abd-El-Aleem S, Morales-Aza B. A model of periodontitis in the rat: effect of lipopolysaccharide on bone resorption, osteoclast activity, and local peptidergic innervation. J Clin Periodontol, 2004, 31(8): 596-603.

[7] Fentoglu O, Koroglu BK, Hicyilmaz H. Pro-inflammatory cytokine levels in association between periodontal disease and hyperlipidaemia. J Clin Periodontol, 2011, 38(1): 8-16.

[8] Noh MK, Jung M, Kim SH. Assessment of IL-6, IL-8 and TNF-alpha levels in the gingival tissue of patients with periodontitis. Exp Ther Med, 2013, 6(3): 847-851.

[9] Maeno M, Tanaka H, Zhang F. Direct and indirect effects of IL-17A on RANKL-induced osteoclastogenesis. J Hard Tissue Biol, 2013, 22(3): 287-292.

[10] Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res, 2010, 89(12): 1349-1363.

[11] Graves D. Cytokines that promote periodontal tissue destruction. J Periodontol, 2008, 79(8 Suppl): 1585-1591.

[12] Fonseca JE, Santos MJ, Canhao H. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev, 2009, 8(7): 538-542.

[13] Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol, 2003, 74(3): 391-401.

[14] Okada N, Kobayashi M, Mugikura K. Interleukin-6 production in human fibroblasts derived from periodontal tissues is differentially regulated by cytokines and a glucocorticoid. J Periodontal Res, 1997, 32(7): 559-569.

[15] Garlet GP, Cardoso CR, Campanelli AP. The dual role of p55 tumour necrosis factor-alpha receptor in Actinobacillus actinomycetemcomitans-induced experimental periodontitis: host protection and tissue destruction. Clin Exp Immunol, 2007, 147(1): 128-138.

[16] Musacchio E, Valvason C, Botsios C. The tumor necrosis factor-α-blocking agent infliximab inhibits interleukin 1beta (IL-1beta) and IL-6 gene expression in human osteoblastic cells. J Rheumatol, 2009, 36(8): 1575-1579.

[17] Jones KJ, Ekhlassi S, Montufar-Solis D. Differential cytokine patterns in mouse macrophages and gingival fibroblasts after stimulation with Porphyromonas gingivalis or Escherichia coli lipopolysaccharide. J Periodontol, 2010, 81(12): 1850-1857.

[18] Andrukhov O, Ertlschweiger S, Moritz A. Different effects of P. gingivalis LPS and E. coli LPS on the expression of interleukin-6 in human gingival fibroblasts. Acta Odontol Scand, 2014, 72(5): 337-345.

[19] Plock N, Kloft C. Microdialysis–theoretical background and recent implementation in applied life-sciences. Eur J Pharm Sci, 2005, 25(1): 1-24.

[20] de la Pena A, Liu P, Derendorf H. Microdialysis in peripheral tissues. Adv Drug Deliv Rev, 2000, 45(2/3): 189-216.

[21] Sugiyama A, Uehara A, Iki K. Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1. J Med Microbiol, 2002, 51(1): 27-33.

[22] Nebel D, Arvidsson J, Lillqvist J. Differential effects of LPS from Escherichia coli and Porphyromonas gingivalis on IL-6 production in human periodontal ligament cells. Acta Odontol Scand, 2013, 71(3/4): 892-898.

[23] Burns E, Eliyahu T, Uematsu S. TLR2-dependent inflammatory response to Porphyromonas gingivalis is MyD88 independent, whereas MyD88 is required to clear infection. J Immunol, 2010, 184(3): 1455-1462.

[24] Hajishengallis G, Lambris JD. Complement and dysbiosis in periodontal disease. Immunobiology, 2012, 217(11): 1111-1116.

[25] Koyama S, Sato E, Nomura H. The potential of various lipopolysaccharides to release monocyte chemotactic activity from lung epithelial cells and fibroblasts. Eur Respir J, 1999, 14(3): 545-552.

[26] Saigusa T, Aono Y, Sekino R. Contribution of vesicular and cytosolic dopamine to the increased striatal dopamine efflux elicited by intrastriatal injection of SKF38393. Eur J Pharmacol, 2009, 624(1/2/3): 10-15.

[27] Selleri S, Arnaboldi F, Palazzo M. Toll-like receptor agonists regulate beta-defensin 2 release in hair follicle. Br J Dermatol, 2007, 156(6): 1172-1177.

[28] Bette M, Schlimme S, Mutters R. Influence of different anaesthetics on pro-inflammatory cytokine expression in rat spleen. Lab Anim, 2004, 38(3): 272-279.

[29] Dornelles FN, Santos DS, Van Dyke TE. In vivo up-regulation of kinin B1 receptors after treatment with Porphyromonas gingivalis lipopolysaccharide in rat paw. J Pharmacol Exp Ther, 2009, 330(3): 756-763.

[30] Darveau RP, Pham TT, Lemley K. Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both toll-like receptors 2 and 4. Infect Immun, 2004, 72(9): 5041-5051.

[31] Costalonga M, Batas L, Reich BJ. Effects of Toll-like receptor 4 on Porphyromonas gingivalis-induced bone loss in mice. J Periodontal Res, 2009, 44(4): 537-542.

[32] Zhang D, Chen L, Li S. Lipopolysaccharide (LPS) of Porphyromonas gingivalis induces IL-1beta, TNF-alpha and IL-6 production by THP-1 cells in a way different from that of Escherichia coli LPS. Innate Immun, 2008, 14(2): 99-107.

[33] Ekhlassi S, Scruggs LY, Garza T. Porphyromonas gingivalis lipopolysaccharide induces tumor necrosis factor-α and interleukin-6 secretion, and CCL25 gene expression, in mouse primary gingival cell lines: interleukin-6-driven activation of CCL2. J Periodontal Res, 2008, 43(4): 431-439.

[34] Andrian E, Grenier D, Rouabhia M. Porphyromonas gingivalis lipopolysaccharide induces shedding of syndecan-1 expressed by gingival epithelial cells. J Cell Physiol, 2005, 204(1): 178-183.

[35] Beklen A, Sorsa T, Konttinen YT. Toll-like receptors 2 and 5 in human gingival epithelial cells co-operate with T-cell cytokine interleukin-17. Oral Microbiol Immunol, 2009, 24(1): 38-42.

[36] Matsushita K, Tajima T, Tomita K. Inflammatory cytokine production and specific antibody responses to lipopolysaccharide from endodontopathic black-pigmented bacteria in patients with multilesional periapical periodontitis. J Endod, 1999, 25(12): 795-799.

[37] Chen LL, Yan J. Porphyromonas gingivalis lipopolysaccharide activated bone resorption of osteoclasts by inducing IL-1, TNF, and PGE. Acta Pharmacol Sin, 2001, 22(7): 614-618.