Role of Fusobacterium nucleatum in periodontal health and disease

Current Issues in Molecular Biology

Volumn 13, Issue 2, 2011, Pages 25-36

  Signat, Benoit ^a   Roques, Christine ^a   Poulet, Pierre ^a   Duffaut, Danielle ^a  

^a UNIVERSITÉ PAUL SABATIER   (France)

Author keywords

[No Author keywords available]

Indexed keywords

BETA DEFENSIN; BETA DEFENSIN 2; BETA DEFENSIN 3; CATHELICIDIN ANTIMICROBIAL PEPTIDE LL 37; DEFENSIN; INTERLEUKIN 8; ANTIMICROBIAL CATIONIC PEPTIDE;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC SENSITIVITY; ARTICLE; BACTERIAL VIRULENCE; BIOLOGICAL ACTIVITY; COMMENSALISM; CONCENTRATION RESPONSE; CYTOKINE PRODUCTION; CYTOKINE RELEASE; DISEASE PREDISPOSITION; DRUG EFFICACY; DRUG POTENCY; FUSOBACTERIUM INFECTION; FUSOBACTERIUM NUCLEATUM; HOST CELL; HUMAN; IMMUNOMODULATION; IMMUNOREACTIVITY; INNATE IMMUNITY; MOUTH CAVITY; MOUTH FLORA; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PERIODONTAL DISEASE; PROTEIN EXPRESSION; PROTEIN FUNCTION; DRUG EFFECT; HEALTH; HOST PATHOGEN INTERACTION; IMMUNOLOGY; MICROBIOLOGY; PATHOLOGY; PERIODONTIUM; PHYSIOLOGY; REVIEW;

FUSOBACTERIUM NUCLEATUM; NEGIBACTERIA;

ANTIMICROBIAL CATIONIC PEPTIDES; FUSOBACTERIUM NUCLEATUM; HEALTH; HOST-PATHOGEN INTERACTIONS; HUMANS; PERIODONTAL DISEASES; PERIODONTIUM;

EID: 79851496489     PISSN: 14673037     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (145)

1. Acheson DW, Luccioli S. Microbial-gut interactions in health and disease (2004). Mucosal immune responses. Best Pract Res Clin Gastroenterol. 18: 387-404.
2. Ali RS, Falconer A, Ikram M, Bissett CE, Cerio R, Quinn AG. (2001). Expression of the peptide antibiotics human beta defensin-1 and human beta defensin-2 in normal human skin. J Invest Dermatol. 117: 106-11.
3. Bachrach G, Rosen G, Bellalou M, Naor R, Sela MN. (2004). Identification of a Fusobacterium nucleatum 65 kDa serine protease. Oral Microbiol Immunol. 19: 155-9.
4. Birkedal-Hansen H. (1993). Role of cytokines and inflammatory mediators in tissue destruction. J Periodontal Res. 28(6 Pt 2): 500-10.
5. Bissell J, Joly S, Johnson GK, Organ CC, Dawson D, McCray PB Jr, Guthmiller JM. (2004). Expression of betadefensins in gingival health and in periodontal disease. J Oral Pathol Med. 2004 May;33: 278- 85.
6. Bolstad AI, Jensen HB, Bakken V. (1996). Taxonomy, biology, and periodontal aspects of Fusobacterium nucleatum. Clin Microbiol Rev. 9: 55-71.
7. Boman HG. (2000). Innate immunity and the normal microflora. Immunol Rev. 173: 5-16.
8. Boniotto M, Jordan WJ, Eskdale J, Tossi A, Antcheva N, Crovella S, Connell ND, Gallagher G. (2006). Human beta-defensin 2 induces a vigorous cytokine response in peripheral blood mononuclear cells. Antimicrob Agents Chemother. 50: 1433-41.
9. Brissette CA, Lukehart SA. (2002). Treponema denticola is resistant to human beta- defensins. Infect Immun. 70: 3982-4.
10. Brissette CA, Lukehart SA. (2007). Mechanisms of decreased susceptibility to beta- defensins by Treponema denticola. Infect Immun. 75: 2307-15.
11. Chung WO, Dommisch H, Yin L, Dale BA. (2007). Expression of defensins in gingiva and their role in periodontal health and disease. Curr Pharm Des. 13: 3073-83.
12. Chung WO, Dale BA. (2004). Innate immune response of oral and foreskin keratinocytes: utilization of different signaling pathways by various bacterial species. Infect Immun. 72: 352-8.
13. Chung WO, Hansen SR, Rao D, Dale BA. (2004). Protease-activated receptor signaling increases epithelial antimicrobial peptide expression. J Immunol. 2004 15;173: 5165-70.
14. Curtis MA, Aduse-Opoku J, Rangarajan M. (2001). Cysteine proteases of Porphyromonas gingivalis. Crit Rev Oral Biol Med. 12: 192-216.
15. D'Aiuto F, Parkar M, Andreou G, Suvan J, Brett PM, Ready D, Tonetti MS. (2004). Periodontitis and systemic inflammation: control of the local infection is associated with a reduction in serum inflammatory markers. J Dent Res. 83: 156-60.
16. Dale BA, Fredericks LP. (2005). Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol. 7: 119-33.
17. Dale BA, Krisanaprakornkit S. (2001). Defensin antimicrobial peptides in the oral cavity. J Oral Pathol Med. 30: 321-7.
18. Dale BA, Kimball JR, Krisanaprakornkit S, Roberts F, Robinovitch M, O'Neal R, Valore EV, Ganz T, Anderson GM, Weinberg A. (2001). Localized antimicrobial peptide expression in human gingiva. J Periodontal Res. 36: 285-94.
19. Dale BA. (2002). Periodontal epithelium: a newly recognized role in health and disease. Periodontol 2000. 30: 70-8.
20. Darby IB, Mooney J, Kinane DF. (2001). Changes in subgingival microflora and humoral immune response following periodontal therapy. J Clin Periodontol. 28: 796-805.
21. Darveau RP, Tanner A, Page RC. (1997). The microbial challenge in periodontitis. Periodontol 2000. 14: 12-32.
22. De Smet K, Contreras R. (2005). Human antimicrobial peptides: defensins, cathelicidins and histatins. Biotechnol Lett. 27: 1337-47.
23. Delima AJ, Karatzas S, Amar S, Graves DT. (2002). Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists. J Infect Dis. 2002 Aug 15;186: 511-6.
24. Delima AJ, Oates T, Assuma R, Schwartz Z, Cochran D, Amar S, Graves DT. (2001). Soluble antagonists to interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibits loss of tissue attachment in experimental periodontitis. J Clin Periodontol. 28: 233-40.
25. Demuth DR, Savary R, Golub E, Shenker BJ. (1996). Identification and analysis of fipA, a Fusobacterium nucleatum immunosuppressive factor gene. Infect Immun. 64: 1335-41.
26. Diamond G, Bevins CL. (1998). beta-Defensins: endogenous antibiotics of the innate host defense response. Clin Immunol Immunopathol. 88: 221-5.
27. Diamond DL, Kimball JR, Krisanaprakornkit S, Ganz T, Dale BA. (2001). Detection of beta- defensins secreted by human oral epithelial cells. J Immunol Methods. 256(1- 2): 65-76.
28. Dinulos JG, Mentele L, Fredericks LP, Dale BA, Darmstadt GL. (2003). Keratinocyte expression of human beta defensin 2 following bacterial infection: role in cutaneous host defense. Clin Diagn Lab Immunol. 10: 161-6.
29. Dixon DR, Bainbridge BW, Darveau RP. (2004). Modulation of the innate immune response within the periodontium. Periodontol 2000. 35: 53-74.
30. Dommisch H, Açil Y, Dunsche A, Winter J, Jepsen S. (2005). Differential gene expression of human beta-defensins (hBD-1, -2, -3) in inflammatory gingival diseases. Oral Microbiol Immunol. 20: 186-90.
31. Dongari-Bagtzoglou AI, Ebersole JL. (1996). Production of inflammatory mediators and cytokines by human gingival fibroblasts following bacterial challenge. J Periodontal Res. 31: 90-8.
32. Dunsche A, Açil Y, Siebert R, Harder J, Schröder JM, Jepsen S. (2001). Expression profile of human defensins and antimicrobial proteins in oral tissues. J Oral Pathol Med. 30: 154-8.
33. Dürr M, Peschel A. (2002). Chemokines meet defensins: the merging concepts of chemoattractants and antimicrobial peptides in host defense. Infect Immun. 70: 6515-7.
34. Dye BA, Choudhary K, Shea S, Papapanou PN. (2005). Serum antibodies to periodontal pathogens and markers of systemic inflammation. J Clin Periodontol. 32: 1189-99.
35. Dzink JL, Socransky SS, Haffajee AD. (1988). The predominant cultivable microbiota of active and inactive lesions of destructive periodontal diseases. J Clin Periodontol. 15: 316-23.
36. Feng Z, Weinberg A. (2006). Role of bacteria in health and disease of periodontal tissues. Periodontol 2000. 40: 50-76.
37. Fenno JC, Lee SY, Bayer CH, Ning Y. (2001). The opdB locus encodes the trypsin- like peptidase activity of Treponema denticola. Infect Immun. 69: 6193-200.
38. Frohm M, Agerberth B, Ahangari G, Stâhle-Bäckdahl M, Lidén S, Wigzell H, Gudmundsson GH. (1997). The expression of the gene coding for the antibacterial peptide LL- 37 is induced in human keratinocytes during inflammatory disorders. J Biol Chem. 272: 15258-63.
39. Frye M, Bargon J, Gropp R. (2001). Expression of human beta-defensin-1 promotes differentiation of keratinocytes. J Mol Med. 79(5-6): 275-82.
40. Ganz T. (2003). Defensins: antimicrobial peptides of innate immunity. Nat Rev Immunol. 3: 710-20.
41. Ganz T, Lehrer RI. (1995). Defensins. Pharmacol Ther. 66: 191-205.
42. Gemmell E, Carter CL, Seymour GJ. (2001). Chemokines in human periodontal disease tissues. Clin Exp Immunol. 125: 134-41.
43. Gibbons RJ, van Houte J. (1971). Selective Bacterial Adherence to Oral Epithelial Surfaces and Its Role as an Ecological Determinant. Infect Immun. 3: 567-573.
44. Gursoy UK, Könönen E, Uitto VJ. (2008). Stimulation of epithelial cell matrix metalloproteinase (MMP-2, -9, -13) and interleukin-8 secretion by fusobacteria. Oral Microbiol Immunol. 23: 432-4.
45. Haffajee AD, Socransky SS, Patel MR, Song X. (2008). Microbial complexes in supragingival plaque. Oral Microbiol Immunol. 2008 Jun: 196-205.
46. Haffajee AD, Socransky SS. (1994). Microbial etiological agents of destructive periodontal diseases. Periodontol 2000. 5: 78-111.
47. Han YW, Shi W, Huang GT, Kinder Haake S, Park NH, Kuramitsu H, Genco RJ. (2000). Interactions between periodontal bacteria and human oral epithelial cells: Fusobacterium nucleatum adheres to and invades epithelial cells. Infect Immun. 68: 3140-6.
48. Hanazawa S, Kawata Y, Takeshita A, Kumada H, Okithu M, Tanaka S, Yamamoto Y, Masuda T, Umemoto T, Kitano S. (1993). Expression of monocyte chemoattractant protein 1 (MCP-1) in adult periodontal disease: increased monocyte chemotactic activity in crevicular fluids and induction of MCP-1 expression in gingival tissues. Infect Immun.61: 5219-24.
49. Hancock RE. (1997). Peptide antibiotics. Lancet.349: 418- 22.
50. Harder J, Bartels J, Christophers E, Schröder JM. (1997). A peptide antibiotic from human skin. Nature. 387(6636): 861.
51. Harder J, Bartels J, Christophers E, Schroder JM. (2001). Isolation and characterization of human beta -defensin-3, a novel human inducible peptide antibiotic. J Biol Chem. 276: 5707-13.
52. Harder J, Meyer-Hoffert U, Wehkamp K, Schwichtenberg L, Schröder JM. (2004). Differential gene induction of human beta-defensins (hBD-1, -2, -3, and -4) in keratinocytes is inhibited by retinoic acid. J Invest Dermatol. 123: 522-9.
53. Hasegawa Y, Mans JJ, Mao S, Lopez MC, Baker HV, Handfield M, Lamont RJ. (2007). Gingival epithelial cell transcriptional responses to commensal and opportunistic oral microbial species. Infect Immun. 75: 2540-7.
54. Holzhausen M, Spolidorio LC, Ellen RP, Jobin MC, Steinhoff M, Andrade-Gordon P, Vergnolle N. (2006). Proteaseactivated receptor-2 activation: a major role in the pathogenesis of Porphyromonas gingivalis infection. Am J Pathol. 168: 1189-99.
55. Holzhausen M, Spolidorio LC, Vergnolle N. (2005). Role of protease-activated receptor-2 in inflammation, and its possible implications as a putative mediator of periodontitis. Mem Inst Oswaldo Cruz. 100 Suppl 1: 177-80.
56. Huang GT, Zhang HB, Dang HN, Haake SK. (2004). Differential regulation of cytokine genes in gingival epithelial cells challenged by Fusobacterium nucleatum and Porphyromonas gingivalis. Microb Pathog. 37: 303-12.
57. Ishikawa I. (2007). Host responses in periodontal diseases: a preview. Periodontol 2000. 43: 9-13.
58. Izadpanah A, Gallo RL. (2005). Antimicrobial peptides. J Am Acad Dermatol. 52(3 Pt 1): 381-90
59. Jewett A, Hume WR, Le H, Huynh TN, Han YW, Cheng G, Shi W. (2000). Induction of apoptotic cell death in peripheral blood mononuclear and polymorphonuclear cells by an oral bacterium, Fusobacterium nucleatum. Infect Immun. 68: 1893-8.
60. Ji S, Kim Y, Min BM, Han SH, Choi Y. (2007). Innate immune responses of gingival epithelial cells to nonperiodontopathic and periodontopathic bacteria. J Periodontal Res. 42: 503-10.
61. Ji S, Hyun J, Park E, Lee BL, Kim KK, Choi Y. (2007). Susceptibility of various oral bacteria to antimicrobial peptides and phagocytosis by neutrophils J Periodontal Res. 42: 410-9.
62. Ji S, Shin JE, Kim YS, Oh JE, Min BM, Choi Y. (2009). Tolllike receptor 2 and NALP2 mediate induction of human beta-defensins by Fusobacterium nucleatum in gingival epithelial cells. Infect Immun. 77: 1044-52.
63. Jia HP, Schutte BC, Schudy A, Linzmeier R, Guthmiller JM, Johnson GK, Tack BF, Mitros JP, Rosenthal A, Ganz T, McCray PB Jr. (2001). Discovery of new human betadefensins using a genomics-based approach. Gene. 263(1-2): 211-8.
64. Joly S, Maze C, McCray PB Jr, Guthmiller JM. (2004). Human beta-defensins 2 and 3 demonstrate strainselective activity against oral microorganisms. J Clin Microbiol. 42: 1024-9.
65. Jonard L., Ban L., Pressac M., Just J. and Bahuau M. (2006). Les défensines en physiopathologie humaine. Immunoanalyse and Biologie Spécialisée. 342-347
66. Kagan BL, Ganz T, Lehrer RI. (1994). Defensins: a family of antimicrobial and cytotoxic peptides. Toxicology. 87(1-3): 131-49.
67. Kagnoff MF, Eckmann L. (1997). Epithelial cells as sensors for microbial infection. J Clin Invest. 100: 6-10.
68. Karpathy SE, Qin X, Gioia J, Jiang H, Liu Y, Petrosino JF, Yerrapragada S, Fox GE, Haake SK, Weinstock GM, Highlander SK. (2007). Genome sequence of Fusobacterium nucleatum subspecies polymorphum - a genetically tractable fusobacterium. PLoS One. 2: e659.
69. Kikkert R, Laine ML, Aarden LA, van Winkelhoff AJ. (2007). Activation of toll-like receptors 2 and 4 by gram-negative periodontal bacteria. Oral Microbiol Immunol. 22: 145-51.
70. Kinder SA, Holt SC. (1993). Localization of the Fusobacterium nucleatum T18 adhesin activity mediating coaggregation with Porphyromonas gingivalis T22. J Bacteriol. 175: 840-50.
71. Kinder Haake S, Lindemann RA. (1997). Fusobacterium nucleatum T18 aggregates human mononuclear cells and inhibits their PHA-stimulated proliferation. J Periodontol. 68: 39-44.
72. Kolenbrander PE, Andersen RN, Blehert DS, Egland PG, Foster JS, Palmer RJ Jr. (2002). Communication among oral bacteria. Microbiol Mol Biol Rev. 2002: 486-505.
73. Kolenbrander PE. (2000). Oral microbial communities: biofilms, interactions, and genetic systems. Annu Rev Microbiol. 54: 413-37.
74. Kornman KS, Page RC, Tonetti MS. (1997). The host response to the microbial challenge in periodontitis: assembling the players. Periodontol 2000. 14: 33-53.
75. Krisanaprakornkit S, Kimball JR, Weinberg A, Darveau RP, Bainbridge BW, Dale BA. (2000). Inducible expression of human beta-defensin 2 by Fusobacterium nucleatum in oral epithelial cells: multiple signaling pathways and role of commensal bacteria in innate immunity and the epithelial barrier. Infect Immun. 68: 2907-15.
76. Krisanaprakornkit S, Weinberg A, Perez CN, Dale BA. (1998). Expression of the peptide antibiotic human betadefensin 1 in cultured gingival epithelial cells and gingival tissue. Infect Immun. 66: 4222-8.
77. Krisanaprakornkit S, Jotikasthira D, Dale BA. (2003). Intracellular calcium in signaling human beta-defensin-2 expression in oral epithelial cells. J Dent Res. 82: 877-82.
78. Krisanaprakornkit S, Kimball JR, Dale BA. (2002). Regulation of human beta- defensin-2 in gingival epithelial cells: the involvement of mitogen- activated protein kinase pathways, but not the NF-kappaB transcription factor family. J Immunol. 168: 316-24.
79. Lah TT, Babnik J, Schiffmann E, Turk V, Skaleric U. (1993). Cysteine proteinases and inhibitors in inflammation: their role in periodontal disease. J Periodontol. 64(5 Suppl): 485-91.
80. Lamont RJ, Yilmaz O. (2002). In or out: the invasiveness of oral bacteria. Periodontol 2000. 30: 61-9.
81. Li J, Helmerhorst EJ, Leone CW, Troxler RF, Yaskell T, Haffajee AD, Socransky SS, Oppenheim FG. (2004). Identification of early microbial colonizers in human dental biofilm. J Appl Microbiol. 97: 1311-8.
82. Liu AY, Destoumieux D, Wong AV, Park CH, Valore EV, Liu L, Ganz T. (2002). Human beta- defensin-2 production in keratinocytes is regulated by interleukin-1, bacteria, and the state of differentiation. J Invest Dermatol. 118: 275-81.
83. Liu L, Wang L, Jia HP, Zhao C, Heng HH, Schutte BC, McCray PB Jr, Ganz T. (1998). Structure and mapping of the human beta-defensin HBD-2 gene and its expression at sites of inflammation. Gene. 222: 237-44.
84. Liu RK, Cao CF, Meng HX, Gao Y. (2001). Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis. J Periodontol. 72: 1545-53.
85. Lu Q, Samaranayake LP, Darveau RP, Jin L. (2005). Expression of human beta- defensin-3 in gingival epithelia. J Periodontal Res. 40: 474-81.
86. Lu Q, Jin L, Darveau RP, Samaranayake LP. (2004). Expression of human beta- defensins-1 and -2 peptides in unresolved chronic periodontitis. J Periodontal Res. 2004 Aug;39: 221-7.
87. Madianos PN, Bobetsis YA, Kinane DF. (2005). Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol. 32 Suppl 6: 57-71.
88. Mahanonda R, Pichyangkul S. (2007). Toll-like receptors and their role in periodontal health and disease. Periodontol 2000. 43: 41-55.
89. Maisetta G, Batoni G, Esin S, Luperini F, Pardini M, Bottai D, Florio W, Giuca MR, Gabriele M, Campa M. (2003). Activity of human beta-defensin 3 alone or combined with other antimicrobial agents against oral bacteria. Antimicrob Agents Chemother. 2003: 3349-51.
90. Marshall RI. (2004). Gingival defensins: linking the innate and adaptive immune responses to dental plaque. Periodontol 2000. 35: 14-20.
91. Mathews M, Jia HP, Guthmiller JM, Losh G, Graham S, Johnson GK, Tack BF, McCray PB Jr. (1999). Production of beta-defensin antimicrobial peptides by the oral mucosa and salivary glands. Infect Immun. 67: 2740-5.
92. Mavris M, Sansonetti P. (2004). Microbial-gut interactions in health and disease. Epithelial cell responses. Best Pract Res Clin Gastroenterol. 18: 373-86.
93. Metzger Z, Blasbalg J, Dotan M, Tsesis I, Weiss EI. (2009). Characterization of coaggregation of Fusobacterium nucleatum PK1594 with six Porphyromonas gingivalis strains. J Endod. 35: 50-4.
94. Metzger Z, Blasbalg J, Dotan M, Weiss EI. (2009). Enhanced attachment of Porphyromonas gingivalis to human fibroblasts mediated by Fusobacterium nucleatum. J Endod. 35: 82-5.
95. Mineshiba F, Takashiba S, Mineshiba J, Matsuura K, Kokeguchi S, Murayama Y. (2003). Antibacterial activity of synthetic human B defensin-2 against periodontal bacteria. J Int Acad Periodontol. 5: 35-40.
96. Moore WE, Moore LV. (1994). The bacteria of periodontal diseases. Periodontol 2000. 5: 66-77.
97. Murakami M, Ohtake T, Dorschner RA, Schittek B, Garbe C, Gallo RL. (2002). Cathelicidin anti-microbial peptide expression in sweat, an innate defense system for the skin. J Invest Dermatol. 119: 1090-5.
98. Murakami M, Ohtake T, Dorschner RA, Gallo RL. (2002). Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva. J Dent Res. 81: 845-50.
99. Nishihara T, Koseki T. (2004). Microbial etiology of periodontitis. Periodontol 2000. 36: 14-26.
100. Niyonsaba F, Ushio H, Nakano N, Ng W, Sayama K, Hashimoto K, Nagaoka I, Okumura K, Ogawa H. (2007). Antimicrobial peptides human beta-defensins stimulate epidermal keratinocyte migration, proliferation and production of proinflammatory cytokines and chemokines. J Invest Dermatol. 127: 594-604.
101. Niyonsaba F, Someya A, Hirata M, Ogawa H, Nagaoka I. (2001). Evaluation of the effects of peptide antibiotics human beta-defensins-1/-2 and LL-37 on histamine release and prostaglandin D production from mast cells. Eur J Immunol. 31: 1066-75.
102. Niyonsaba F, Ogawa H, Nagaoka I. (2004). Human betadefensin- 2 functions as a chemotactic agent for tumour necrosis factor-alpha-treated human neutrophils. Immunology. 111: 273-81.
103. Niyonsaba F, Ushio H, Nagaoka I, Okumura K, Ogawa H. (2005). The human beta- defensins (-1, -2, -3, -4) and cathelicidin LL-37 induce IL-18 secretion through p38 and ERK MAPK activation in primary human keratinocytes. J Immunol. 175: 1776-84.
104. Niyonsaba F, Iwabuchi K, Matsuda H, Ogawa H, Nagaoka I. (2002). Epithelial cell- derived human beta-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway. Int Immunol. 14: 421-6.
105. Niyonsaba F, Iwabuchi K, Someya A, Hirata M, Matsuda H, Ogawa H, Nagaoka I. (2002). A cathelicidin family of human antibacterial peptide LL-37 induces mast cell chemotaxis. Immunology. 106: 20-6.
106. Nizet V, Ohtake T, Lauth X, Trowbridge J, Rudisill J, Dorschner RA, Pestonjamasp V, Piraino J, Huttner K, Gallo RL. (2001). Innate antimicrobial peptide protects the skin from invasive bacterial infection. Nature. 414(6862): 454-7.
107. Ogawa AT, Brasil de Souza Tde A, de Uzeda M, Jankevicius JV, Jankevicius SI. (2006). Characterization of proteolytic activities of Fusobacterium nucleatum. J Endod. 32: 521-3.
108. Okada H, Murakami S. (1998). Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med. 9: 248-66.
109. Oppenheim JJ, Biragyn A, Kwak LW, Yang D. (2003). Roles of antimicrobial peptides such as defensins in innate and adaptive immunity. Ann Rheum Dis. 62 Suppl 2: ii17-21.
110. Ouhara K, Komatsuzawa H, Yamada S, Shiba H, Fujiwara T, Ohara M, Sayama K, Hashimoto K, Kurihara H, Sugai M. (2005). Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, {beta}- defensins and LL37, produced by human epithelial cells. J Antimicrob Chemother. 55: 888-96
111. Page RC, Schroeder HE. (1976). Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 34: 235-49.
112. Pütsep K, Carlsson G, Boman HG, Andersson M. (2002). Deficiency of antibacterial peptides in patients with morbus Kostmann: an observation study. Lancet. 360(9340): 1144-9.
113. Raj PA, Dentino AR. (2002). Current status of defensins and their role in innate and adaptive immunity. FEMS Microbiol Lett. 206: 9-18.
114. Sahasrabudhe KS, Kimball JR, Morton TH, Weinberg A, Dale BA. (2000). Expression of the antimicrobial peptide, human beta-defensin 1, in duct cells of minor salivary glands and detection in saliva. J Dent Res. 79: 1669-74.
115. Saito A, Inagaki S, Kimizuka R, Okuda K, Hosaka Y, Nakagawa T, Ishihara K. (2008). Fusobacterium nucleatum enhances invasion of human gingival epithelial and aortic endothelial cells by Porphyromonas gingivalis. FEMS Immunol Med Microbiol. 54: 349-55.
116. Schenkein HA. (2006). Host responses in maintaining periodontal health and determining periodontal disease. Periodontol 2000. 40: 77-93.
117. Schonwetter BS, Stolzenberg ED, Zasloff MA. (1995). Epithelial antibiotics induced at sites of inflammation. Science. 267(5204): 1645-8.
118. Schröder JM. (1999). Epithelial antimicrobial peptides: innate local host response elements. Cell Mol Life Sci. 56(1-2): 32-46.
119. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE. (2002). The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol. 169: 3883-91.
120. Seymour GJ, Gemmell E. (2001). Cytokines in periodontal disease: where to from here? Acta Odontol Scand. 59: 167-73.
121. Shenker BJ, DiRienzo JM. (1984). Suppression of human peripheral blood lymphocytes by Fusobacterium nucleatum. J Immunol. 132: 2357-62.
122. Sørensen OE, Thapa DR, Rosenthal A, Liu L, Roberts AA, Ganz T. (2005). Differential regulation of beta-defensin expression in human skin by microbial stimuli. J Immunol. 174: 4870-9.
123. Starner TD, Swords WE, Apicella MA, McCray PB Jr. (2002). Susceptibility of nontypeable Haemophilus influenzae to human beta-defensins is influenced by lipooligosaccharide acylation. Infect Immun. 70: 5287-9.
124. Stolzenberg ED, Anderson GM, Ackermann MR, Whitlock RH, Zasloff M. (1997). Epithelial antibiotic induced in states of disease. Proc Natl Acad Sci U S A. 94: 8686-90.
125. Suchett-Kaye G, Morrier JJ, Barsotti O. (1998). Interactions between non-immune host cells and the immune system during periodontal disease: role of the gingival keratinocyte. Crit Rev Oral Biol Med. 9: 292-305.
126. Supp DM, Karpinski AC, Boyce ST. (2004). Expression of human beta-defensins HBD-1, HBD- 2, and HBD-3 in cultured keratinocytes and skin substitutes. Burns. 30: 643-8.
127. Taggart CC, Greene CM, Smith SG, Levine RL, McCray PB Jr, O'Neill S, McElvaney NG. (2003). Inactivation of human beta-defensins 2 and 3 by elastolytic cathepsins. J Immunol. 171: 931-7.
128. Tezal M, Scannapieco FA, Wactawski-Wende J, Grossi SG, Genco RJ. (2006). Supragingival plaque may modify the effects of subgingival bacteria on attachment loss. J Periodontol. 77: 808-13.
129. Uehara A, Sugawara S, Muramoto K, Takada H. (2002). Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2. J Immunol. 169: 4594-603.
130. Uehara A, Sugawara S, Takada H. (2002). Priming of human oral epithelial cells by interferon-gamma to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans. J Med Microbiol. 51: 626-34.
131. Uitto VJ, Baillie D, Wu Q, Gendron R, Grenier D, Putnins EE, Kanervo A, Firth JD. (2005). Fusobacterium nucleatum increases collagenase 3 production and migration of epithelial cells. Infect Immun. 73: 1171-9.
132. Van der Reijden WA, Bosch-Tijhof CJ, Strooker H, van Winkelhoff AJ. (2006). prtH in Tannerella forsythensis is not associated with periodontitis. J Periodontol. 77: 586-90.
133. Vankeerberghen A, Nuytten H, Dierickx K, Quirynen M, Cassiman JJ, Cuppens H. (2005). Differential induction of human beta-defensin expression by periodontal commensals and pathogens in periodontal pocket epithelial cells. J Periodontol. 76: 1293-303.
134. Vardar-Sengul S, Demirci T, Sen BH, Erkizan V, Kurulgan E, Baylas H. (2007). Human beta defensin-1 and -2 expression in the gingiva of patients with specific periodontal diseases. J Periodontal Res. 42: 429-37.
135. Weinberg A, Krisanaprakornkit S, Dale BA. (1998). Epithelial antimicrobial peptides: review and significance for oral applications. Crit Rev Oral Biol Med. 9: 399-414.
136. Ximénez-Fyvie LA, Haffajee AD, Socransky SS. (2000). Comparison of the microbiota of supra- and subgingival plaque in health and periodontitis. J Clin Periodontol. 27: 648-57.
137. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J, Anderson M, Schröder JM, Wang JM, Howard OM, Oppenheim JJ. (1999). Beta- defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science.286(5439): 525-8.
138. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ. (2004). Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol. 22: 181-215.
139. Yin L, Dale BA. (2007). Activation of protective responses in oral epithelial cells by Fusobacterium nucleatum and human beta-defensin-2. J Med Microbiol. 56(Pt 7): 976- 87.
140. Yoshimura A, Hara Y, Kaneko T, Kato I. (1997). Secretion of IL-1 beta, TNF-alpha, IL-8 and IL-1ra by human polymorphonuclear leukocytes in response to lipopolysaccharides from periodontopathic bacteria. J Periodontal Res. 1997: 279-86.
141. Yoshioka M, Fukuishi N, Kubo Y, Yamanobe H, Ohsaki K, Kawasoe Y, Murata M, Ishizumi A, Nishii Y, Matsui N, Akagi M. (2008). Human cathelicidin CAP18/LL-37 changes mast cell function toward innate immunity. Biol Pharm Bull. 31: 212-6.
142. Zanetti M, Gennaro R, Romeo D. (1995). Cathelicidins: a novel protein family with a common proregion and a variable C-terminal antimicrobial domain. FEBS Lett. 1995;374: 1-5.
143. Zanetti M, Gennaro R, Scocchi M, Skerlavaj B. (2000). Structure and biology of cathelicidins. Adv Exp Med Biol. 479: 203-18.
144. Zasloff M. (2002). Antimicrobial peptides of multicellular organisms. Nature. 415: 389-95.
145. Zasloff M. (2002). Antimicrobial peptides in health and disease. N Engl J Med. 347: 1199-200.