Suppressive effect of the antimicrobial peptide LL-37 on expression of IL-6, IL-8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts

European Journal of Oral Sciences

Volumn 118, Issue 6, 2010, Pages 574-581

  Inomata, Megumi ^a   Into, Takeshi ^a   Murakami, Yukitaka ^a  

^a ASAHI UNIVERSITY   (Japan)

Author keywords

Human gingival fibroblast; Lipopolysaccharide; LL 37; Porphyromonas gingivalis

Indexed keywords

ANTIMICROBIAL CATIONIC PEPTIDE; AUTACOID; CAP18 LIPOPOLYSACCHARIDE BINDING PROTEIN; CAP18 LIPOPOLYSACCHARIDE-BINDING PROTEIN; CXCL10 PROTEIN, HUMAN; GAMMA INTERFERON INDUCIBLE PROTEIN 10; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 6; INTERLEUKIN 8; LIPID A; LIPOPOLYSACCHARIDE; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE P38;

ARTICLE; CELL CULTURE; CELL SURVIVAL; CYTOLOGY; DRUG EFFECT; EPITHELIUM CELL; FIBROBLAST; FIMBRIA; GINGIVA; HUMAN; IMMUNOLOGY; MOUTH MUCOSA; PARACRINE SIGNALING; PHOSPHORYLATION; PORPHYROMONAS GINGIVALIS;

ANTIMICROBIAL CATIONIC PEPTIDES; CELL SURVIVAL; CELLS, CULTURED; CHEMOKINE CXCL10; EPITHELIAL CELLS; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FIBROBLASTS; FIMBRIAE, BACTERIAL; GINGIVA; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATION MEDIATORS; INTERLEUKIN-6; INTERLEUKIN-8; LIPID A; LIPOPOLYSACCHARIDES; MOUTH MUCOSA; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PARACRINE COMMUNICATION; PHOSPHORYLATION; PORPHYROMONAS GINGIVALIS;

EID: 78649605533     PISSN: 09098836     EISSN: 16000722     Source Type: Journal    
DOI: 10.1111/j.1600-0722.2010.00775.x     Document Type: Article

References (62)

1. Petersen PE, Bourgeois D, Ogawa H, Estupinan-Day S, Ndiaye C. The global burden of oral diseases and risks to oral health. Bull World Health Organ 2005; 83: 661-669.
2. Haffajee AD, Cugini MA, Tanner A, Pollack RP, Smith C, Kent RL Jr, Socransky SS. Subgingival microbiota in healthy, well-maintained elder and periodontitis subjects. J Clin Periodontol 1998; 25: 346-353.
3. Holt SC, Bramanti TE. Factors in virulence expression and their role in periodontal disease pathogenesis. Crit Rev Oral Biol Med 1991; 2: 177-281.
4. Cutler CW, Kalmar JR, Genco CA. Pathogenic strategies of the oral anaerobe, Porphyromonas gingivalis. Trends Microbiol 1995; 3: 45-51.
5. Gibson FC, Genco CA. Porphyromonas gingivalis mediated periodontal disease and atherosclerosis: disparate diseases with commonalities in pathogenesis through TLRs. Curr Pharm Des 2007; 13: 3665-3675.
6. Bainbridge BW, Darveau RP. Porphyromonas gingivalis lipopolysaccharide: an unusual pattern recognition receptor ligand for the innate host defense system. Acta Odontol Scand 2001; 59: 131-138.
7. Darveau RP, Pham TT, Lemley K, Reife RA, Bainbridge BW, Coats SR, Howald WN, Way SS, Hajjar AM. Porphyromonas gingivalis lipopolysaccharide contains multiple lipid A species that functionally interact with both Toll-like receptors 2 and 4. Infect Immun 2004; 72: 5041-5051.
8. Hajishengallis G, Martin M, Schifferle RE, Genco RJ. Counteracting interactions between lipopolysaccharide molecules with differential activation of Toll-like receptors. Infect Immun 2002; 70: 6658-6664.
9. Sawada N, Ogawa T, Asai Y, Makimura Y, Sugiyama A. Toll-like receptor 4-dependent recognition of structurally different forms of chemically synthesized lipid As of Porphyromonas gingivalis. Clin Exp Immunol 2007; 148: 529-536.
10. Asai Y, Ohyama Y, Gen K, Ogawa T. Bacterial fimbriae and their peptides activate human gingival epithelial cells through Toll-like receptor 2. Infect Immun 2001; 69: 7387-7395.
11. Asai Y, Hashimoto M, Fletcher HM, Miyake K, Akira S, Ogawa T. Lipopolysaccharide preparation extracted from Porphyromonas gingivalis lipoprotein-deficient mutant shows a marked decrease in Toll-like receptor 2-mediated signaling. Infect Immun 2005; 73: 2157-2163.
12. Wang PL, Oido-Mori M, Fujii T, Kowashi Y, Kikuchi M, Suetsugu Y, Tanaka J, Azuma Y, Shinohara M, Ohura K. Effect of anti-CD14 antibody on experimental periodontitis induced by Porphyromonas gingivalis lipopolysaccharide. Jpn J Pharmacol 2002; 89: 176-183.
13. Hajishengallis G, Sharma A, Russell MW, Genco RJ. Interactions of oral pathogens with Toll-like receptors: possible role in atherosclerosis. Ann Periodontol 2002; 7: 72-78.
14. De Smet K, Contreras R. Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnol Lett 2005; 27: 1337-1347.
15. Durr UH, Sudheendra US, Ramamoorthy A. LL-37, the only human member of the cathelicidin family of antimicrobial peptides. Biochim Biophys Acta 2006; 1758: 1408-1425.
16. Rosenfeld Y, Papo N, Shai Y. Endotoxin (lipopolysaccharide) neutralization by innate immunity host-defense peptides: peptide properties and plausible modes of action. J Biol Chem 2006; 281: 1636-1643.
17. Mookherjee N, Brown KL, Bowdish DM, Doria S, Falsafi R, Hokamp K, Roche FM, Mu R, Doho GH, Pistolic J, Powers JP, Bryan J, Brinkman FS, Hancock RE. Modulation of the TLR-mediated inflammatory response by the endogenous human host defense peptide LL-37. J Immunol 2006; 176: 2455-2464.
18. Nijnik A, Pistolic J, Wyatt A, Tam S, Hancock RE. Human cathelicidin peptide LL-37 modulates the effects of IFN-γ on APCs. J Immunol 2009; 183: 5788-5798.
19. Lande R, Gregorio J, Facchinetti V, Chatterjee B, Wang YH, Homey B, Cao W, Su B, Nestle FO, Zal T, Mellman I, Schroder JM, Liu YJ, Gilliet M. Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide. Nature 2007; 449: 564-569.
20. Puklo M, Guentsch A, Hiemstra PS, Eick S, Potempa J. Analysis of neutrophil-derived antimicrobial peptides in gingival crevicular fluid suggests importance of cathelicidin LL-37 in the innate immune response against periodontogenic bacteria. Oral Microbiol Immunol 2008; 23: 328-335.
21. Putsep K, Carlsson G, Boman HG, Andersson M. Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet 2002; 360: 1144-1149.
22. Turkoglu O, Emingil G, Kutukculer N, Atilla G. Gingival crevicular fluid levels of cathelicidin LL-37 and interleukin-18 in patients with chronic periodontitis. J Periodontol 2009; 80: 969-976.
23. Shi Y, Kong W, Nakayama K. Human lactoferrin binds and removes the hemoglobin receptor protein of the periodontopathogen Porphyromonas gingivalis. J Biol Chem 2000; 275: 30002-30008.
24. Miles K, Clarke DJ, Lu W, Sibinska Z, Beaumont PE, Davidson DJ, Barr TA, Campopiano DJ, Gray M. Dying and necrotic neutrophils are anti-inflammatory secondary to the release of α-defensins. J Immunol 2009; 183: 2122-2132.
25. Pingel LC, Kohlgraf KG, Hansen CJ, Eastman CG, Dietrich DE, Burnell KK, Srikantha RN, Xiao X, Belanger M, Progulske-Fox A, Cavanaugh JE, Guthmiller JM, Johnson GK, Joly S, Kurago ZB, Dawson DV, Brogden KA. Human β-defensin 3 binds to hemagglutinin B (rHagB), a non-fimbrial adhesin from Porphyromonas gingivalis, and attenuates a pro-inflammatory cytokine response. Immunol Cell Biol 2008; 86: 643-649.
26. Kohlgraf KG, Ackermann A, Lu X, Burnell K, Belanger M, Cavanaugh JE, Xie H, Progulske-Fox A, Brogden KA. Defensins attenuate cytokine responses yet enhance antibody responses to Porphyromonas gingivalis adhesins in mice. Future Microbiol 2010; 5: 115-125.
27. Semple F, Webb S, Li HN, Patel HB, Perretti M, Jackson IJ, Gray M, Davidson DJ, Dorin JR. Human β-defensin 3 has immunosuppressive activity in vitro and in vivo. Eur J Immunol 2010; 40: 1073-1078.
28. Imatani T, Kato T, Minaguchi K, Okuda K. Histatin 5 inhibits inflammatory cytokine induction from human gingival fibroblasts by Porphyromonas gingivalis. Oral Microbiol Immunol 2000; 15: 378-382.
29. Westphal O, Jann K. Bacterial lipopolysaccharides: extraction with phenol-water and further applications to the procedure. Methods Carbohydr Chem 1965; 5: 83.
30. Hashimoto M, Asai Y, Ogawa T. Separation and structural analysis of lipoprotein in a lipopolysaccharide preparation from Porphyromonas gingivalis. Int Immunol 2004; 16: 1431-1437.
31. Ogawa T, Shimauchi H, Hamada S. Mucosal and systemic immune responses in BALB/c mice to Bacteroides gingivalis fimbriae administered orally. Infect Immun 1989; 57: 3466-3471.
32. Momose F, Araida T, Negishi A, Ichijo H, Shioda S, Sasaki S. Variant sublines with different metastatic potentials selected in nude mice from human oral squamous cell carcinomas. J Oral Pathol Med 1989; 18: 391-395.
33. Miyauchi T, Moroyama T, Sakamoto T, Okamoto K, Takada T. Establishment of human tumor cell line (Ueda-1) derived from squamous cell carcinoma of the floor of the mouth. Jpn J Oral Maxillofac Surg 1985; 31: 1347-1351.
34. Into T, Inomata M, Shibata K, Murakami Y. Effect of the antimicrobial peptide LL-37 on Toll-like receptors 2-, 3- and 4-triggered expression of IL-6, IL-8 and CXCL10 in human gingival fibroblasts. Cell Immunol 2010; 264: 104-109.
35. Inomata M, Into T, Nakashima M, Noguchi T, Matsushita K. IL-4 alters expression patterns of storage components of vascular endothelial cell-specific granules through STAT6- and SOCS-1-dependent mechanisms. Mol Immunol 2009; 46: 2080-2089.
36. Bowdish DM, Davidson DJ, Lee K, Scott MG, Hancock RE. Impact of LL-37 on anti-infective immunity. J Leukoc Biol 2005; 77: 451-459.
37. Lee SH, Jun HK, Lee HR, Chung CP, Choi BK. Antibacterial and lipopolysaccharide (LPS)-neutralising activity of human cationic antimicrobial peptides against periodontopathogens. Int J Antimicrob Agents 2010; 35: 138-145.
38. Mikolajczyk-Pawlinska J, Travis J, Potempa J. Modulation of interleukin-8 activity by gingipains from Porphyromonas gingivalis: implications for pathogenicity of periodontal disease. FEBS Lett 1998; 440: 282-286.
39. Wang PL, Sato K, Oido M, Fujii T, Kowashi Y, Shinohara M, Ohura K, Tani H, Kuboki Y. Involvement of CD14 on human gingival fibroblasts in Porphyromonas gingivalis lipopolysaccharide-mediated interleukin-6 secretion. Arch Oral Biol 1998; 43: 687-694.
40. Kinane DF, Shiba H, Stathopoulou PG, Zhao H, Lappin DF, Singh A, Eskan MA, Beckers S, Waigel S, Alpert B, Knudsen TB. Gingival epithelial cells heterozygous for Toll-like receptor 4 polymorphisms Asp299Gly and Thr399Ile are hypo-responsive to Porphyromonas gingivalis. Genes Immun 2006; 7: 190-200.
41. Wang PL, Ohura K. Porphyromonas gingivalis lipopolysaccharide signaling in gingival fibroblasts-CD14 and Toll-like receptors. Crit Rev Oral Biol Med 2002; 13: 132-142.
42. Bowdish DM, Davidson DJ, Speert DP, Hancock RE. The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes. J Immunol 2004; 172: 3758-3765.
43. Kadowaki T, Baba A, Abe N, Takii R, Hashimoto M, Tsukuba T, Okazaki S, Suda Y, Asao T, Yamamoto K. Suppression of pathogenicity of Porphyromonas gingivalis by newly developed gingipain inhibitors. Mol Pharmacol 2004; 66: 1599-1606.
44. Lamont RJ, Chan A, Belton CM, Izutsu KT, Vasel D, Weinberg A. Porphyromonas gingivalis invasion of gingival epithelial cells. Infect Immun 1995; 63: 3878-3885.
45. Madianos PN, Papapanou PN, Nannmark U, Dahlen G, Sandros J. Porphyromonas gingivalis FDC381 multiplies and persists within human oral epithelial cells in vitro. Infect Immun 1996; 64: 660-664.
46. Darveau RP, Belton CM, Reife RA, Lamont RJ. Local chemokine paralysis, a novel pathogenic mechanism for Porphyromonas gingivalis. Infect Immun 1998; 66: 1660-1665.
47. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006; 124: 783-801.
48. Erridge C, Pridmore A, Eley A, Stewart J, Poxton IR. Lipopolysaccharides of Bacteroides fragilis, Chlamydia trachomatis and Pseudomonas aeruginosa signal via Toll-like receptor 2. J Med Microbiol 2004; 53: 735-740.
49. Girard R, Pedron T, Uematsu S, Balloy V, Chignard M, Akira S, Chaby R. Lipopolysaccharides from Legionella and Rhizobium stimulate mouse bone marrow granulocytes via Toll-like receptor 2. J Cell Sci 2003; 116: 293-302.
50. Zhang Y, Gaekwad J, Wolfert MA, Boons GJ. Synthetic tetra-acylated derivatives of lipid A from Porphyromonas gingivalis are antagonists of human TLR4. Org Biomol Chem 2008; 6: 3371-3381.
51. Ogawa T, Asai Y, Makimura Y, Tamai R. Chemical structure and immunobiological activity of Porphyromonas gingivalis lipid A. Front Biosci 2007; 12: 3795-3812.
52. Jerala R. Structural biology of the LPS recognition. Int J Med Microbiol 2007; 297: 353-363.
53. Hiraoka T, Izumi Y, Sueda T. Immunochemical detection of CD14 on human gingival fibroblasts in vitro. Oral Microbiol Immunol 1998; 13: 246-252.
54. Ogawa T, Asai Y, Hashimoto M, Uchida H. Bacterial fimbriae activate human peripheral blood monocytes utilizing TLR2, CD14 and CD11a/CD18 as cellular receptors. Eur J Immunol 2002; 32: 2543-2550.
55. Ji S, Hyun J, Park E, Lee BL, Kim KK, Choi Y. Susceptibility of various oral bacteria to antimicrobial peptides and to phagocytosis by neutrophils. J Periodontal Res 2007; 42: 410-419.
56. Altman H, Steinberg D, Porat Y, Mor A, Fridman D, Friedman M, Bachrach G. In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria. J Antimicrob Chemother 2006; 58: 198-201.
57. Bachrach G, Altman H, Kolenbrander PE, Chalmers NI, Gabai-Gutner M, Mor A, Friedman M, Steinberg D. Resistance of Porphyromonas gingivalis ATCC 33277 to direct killing by antimicrobial peptides is protease independent. Antimicrob Agents Chemother 2008; 52: 638-642.
58. Gutner M, Chaushu S, Balter D, Bachrach G. Saliva enables the antimicrobial activity of LL-37 in the presence of proteases of Porphyromonas gingivalis. Infect Immun 2009; 77: 5558-5563.
59. Duncan L, Yoshioka M, Chandad F, Grenier D. Loss of lipopolysaccharide receptor CD14 from the surface of human macrophage-like cells mediated by Porphyromonas gingivalis outer membrane vesicles. Microb Pathog 2004; 36: 319-325.
60. Tada H, Sugawara S, Nemoto E, Takahashi N, Imamura T, Potempa J, Travis J, Shimauchi H, Takada H. Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production. Infect Immun 2002; 70: 3304-3307.
61. Wakabayashi H, Yamauchi K, Kobayashi T, Yaeshima T, Iwatsuki K, Yoshie H. Inhibitory effects of lactoferrin on growth and biofilm formation of Porphyromonas gingivalis and Prevotella intermedia. Antimicrob Agents Chemother 2009; 53: 3308-3316.
62. Ara T, Kurata K, Hirai K, Uchihashi T, Uematsu T, Imamura Y, Furusawa K, Kurihara S, Wang PL. Human gingival fibroblasts are critical in sustaining inflammation in periodontal disease. J Periodontal Res 2009; 44: 21-27n.