Inflammatory and immune pathways in the pathogenesis of periodontal disease

Ali Cekici, Alpdogan Kantarci, Hatice Hasturk, Thomas E Van Dyke, Ali Cekici, Alpdogan Kantarci, Hatice Hasturk, Thomas E Van Dyke

Abstract

The pathogenesis of periodontitis involves a complex immune/inflammatory cascade that is initiated by the bacteria of the oral biofilm that forms naturally on the teeth. The susceptibility to periodontitis appears to be determined by the host response; specifically, the magnitude of the inflammatory response and the differential activation of immune pathways. The purpose of this review was to delineate our current knowledge of the host response in periodontitis. The role of innate immunity, the failure of acute inflammation to resolve (thus becoming chronic), the cytokine pathways that regulate the activation of acquired immunity and the cells and products of the immune system are considered. New information relating to regulation of both inflammation and the immune response will be reviewed in the context of susceptibility to, and perhaps control of, periodontitis.

© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Figures

Fig. 1
Fig. 1
The immune inflammatory response in periodontitis is complex and involves both innate and acquired immunity. This diagram presents an overview of the effector molecules and effector cells in the pathogenesis of periodontitis based on our current understanding of disease pathways. BCA-1, B cell-attracting chemokine 1; CGRP, calcitonin gene-related peptide; CTLA-4, cytotoxic T-lymphocyte-associated antigen 4; GM-CSF, granulocyte– macrophage colony-stimulating factor; IFN-γ, interferon gamma; Ig-A, immunglobulin A; Ig-G, immunglobulin G; Ig-M, immunglobulin M; IL-1β, interleukin-1beta; IL-2, interleukin-2; IL-3, interleukin-3; IL-4, interleukin-4; IL-5, interleukin-5; IL-6, interleukin-6; IL-8, interleukin-8; IL- 13, interleukin-13; IL-17, interleukin-17; IL-22, interleukin-22; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; MAC, membrane attack complex; MCP-1, macrophage chemotactic protein-1; MDC, macrophage-derived chemokine; MMPs, matrix metalloproteinases; OPG, osteoprotegerin; PGE2, prostaglandin E2; RANTES, regulated and normal T cell expressed and secreted; SDF-1a, stromal cell-derived factor-1alpha; TARC, thymus and activation-regulated chemokine; TGF-β, transforming growth factor beta; Th1, T-helper 1 cell; Th2, T-helper 2 cell; Th17, T-helper 17 cell; TIMP, tissue inhibitor of matrix metalloproteinases; TNF-α, tumor necrosis factor alpha; Treg T-regulatory cell.

References

    1. Alexopoulou L, Holt AC, Medzhitov R, Flavell RA. Recognition of double-stranded RNA and activation of NF-kappaB by toll-like receptor 3. Nature. 2001;413:732–738.
    1. Anderson DM, Maraskovsky E, Billingsley WL, Dougall WC, Tometsko ME, Roux ER, Teepe MC, DuBose RF, Cosman D, Galibert L. A homologue of the TNF receptor and its ligand enhance T-cell growth and dendritic-cell function. Nature. 1997;390:175–179.
    1. Anderson KV. Toll signaling pathways in the innate immune response. Curr Opin Immunol. 2000;12:13–19.
    1. Appay V, van Lier RA, Sallusto F, Roederer M. Phenotype and function of human T lymphocyte subsets: consensus and issues. Cytometry A. 2008;73:975–983.
    1. 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;44:21–27.
    1. Awawdeh L, Lundy FT, Shaw C, Lamey PJ, Linden GJ, Kennedy JG. Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in pulp tissue from painful and healthy human teeth. Int Endod J. 2002;35:30–36.
    1. Baker PJ, Dixon M, Roopenian DC. Genetic control of susceptibility to Porphyromonas gingivalis-induced alveolar bone loss in mice. Infect Immun. 2000;68:5864–5868.
    1. Baldwin AS., Jr The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol. 1996;14:649–683.
    1. Bancroft GJ. The role of natural killer cells in innate resistance to infection. Curr Opin Immunol. 1993;5:503–510.
    1. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, Hong S, Serhan CN. Molecular circuits of resolution: formation and actions of resolvins and protectins. J Immunol. 2005;174:4345–4355.
    1. Bartold PM, Kylstra A, Lawson R. Substance P: an immunohistochemical and biochemical study in human gingival tissues. A role for neurogenic inflammation? J Periodontol. 1994;65:1113–1121.
    1. Beck J, Arbes SJ., Jr . Epidemiology of gingival and periodontal diseases. In: Newman MG, Takei HH, Klokkevold PR, editors. Carranza’s clinical periodontology. St Louis: Saunders/Elsevier; 2006. pp. 110–132.
    1. Behl Y, Siqueira M, Ortiz J, Li J, Desta T, Faibish D, Graves DT. Activation of the acquired immune response reduces coupled bone formation in response to a periodontal pathogen. J Immunol. 2008;181:8711–8718.
    1. Belkaid Y, Tarbell K. Regulatory t cells in the control of host-microorganism interactions (*) Annu Rev Immunol. 2009;27:551–589.
    1. Bellinger DL, Lorton D, Brouxhon S, Felten S, Felten DL. The significance of vasoactive intestinal polypeptide (VIP) in immunomodulation. Adv Neuroimmunol. 1996;6:5–27.
    1. Bendre MS, Montague DC, Peery T, Akel NS, Gaddy D, Suva LJ. Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone. 2003;33:28–37.
    1. Berglundh T, Donati M. Aspects of adaptive host response in periodontitis. J Clin Periodontol. 2005;32(Suppl 6):87–107.
    1. Bhatavadekar NB, Williams RC. Modulation of the host inflammatory response in periodontal disease management: exciting new directions. Int Dent J. 2009;59:305–308.
    1. Birkedal-Hansen H. Role of matrix metalloproteinases in human periodontal diseases. J Periodontol. 1993;64:474–484.
    1. Bloemen V, Schoenmaker T, de Vries TJ, Everts V. Direct cell-cell contact between periodontal ligament fibroblasts and osteoclast precursors synergistically increases the expression of genes related to osteoclastogenesis. J Cell Physiol. 2009;222:565–573.
    1. Bonecchi R, Bianchi G, Bordignon PP, D’Ambrosio D, Lang R, Borsatti A, Sozzani S, Allavena P, Gray PA, Mantovani A, Sinigaglia F. Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med. 1998;187:129–134.
    1. Bracci-Laudiero L, Aloe L, Buanne P, Finn A, Stenfors C, Vigneti E, Theodorsson E, Lundeberg T. NGF modulates CGRP synthesis in human B-lymphocytes: a possible anti-inflammatory action of NGF? J Neuroimmunol. 2002;123:58–65.
    1. Brain SD, Williams TJ, Tippins JR, Morris HR, MacIntyre I. Calcitonin gene-related peptide is a potent vasodilator. Nature. 1985;313:54–56.
    1. Breitfeld D, Ohl L, Kremmer E, Ellwart J, Sallusto F, Lipp M, Forster R. Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production. J Exp Med. 2000;192:1545–1552.
    1. Brown JM, Zhang J, Keller ET. OPG, RANKL, and RANK in cancer metastasis: expression and regulation. Cancer Treat Res. 2004;118:149–172.
    1. Buckley TL, Brain SD, Collins PD, Williams TJ. Inflammatory edema induced by interactions between IL-1 and the neuropeptide calcitonin gene-related peptide. J Immunol. 1991;146:3424–3430.
    1. Burns E, Bachrach G, Shapira L, Nussbaum G. Cutting edge: TLR2 is required for the innate response to Porphyromonas gingivalis: activation leads to bacterial persistence and TLR2 deficiency attenuates induced alveolar bone resorption. J Immunol. 2006;177:8296–8300.
    1. Byers MR, Taylor PE. Effect of sensory denervation on the response of rat molar pulp to exposure injury. J Dent Res. 1993;72:613–618.
    1. Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI. Primary afferent tachykinins are required to experience moderate to intense pain. Nature. 1998;392:390–394.
    1. Cardoso CR, Garlet GP, Moreira AP, Junior WM, Rossi MA, Silva JS. Characterization of CD4+ CD25+ natural regulatory T cells in the inflammatory infiltrate of human chronic periodontitis. J Leukoc Biol. 2008;84:311–318.
    1. Chou WY, Lu CN, Lee TH, Wu CL, Hung KS, Concejero AM, Jawan B, Wang CH. Electroporative interleukin-10 gene transfer ameliorates carbon tetrachloride-induced murine liver fibrosis by MMP and TIMP modulation. Acta Pharmacol Sin. 2006;27:469–476.
    1. Claria J, Lee MH, Serhan CN. Aspirin-triggered lipoxins (15-epi-LX) are generated by the human lung adenocarcinoma cell line (A549)-neutrophil interactions and are potent inhibitors of cell proliferation. Mol Med. 1996;2:583–596.
    1. Claudino M, Trombone AP, Cardoso CR, Ferreira SB, Jr, Martins W, Jr, Assis GF, Santos CF, Trevilatto PC, Campanelli AP, Silva JS, Garlet GP. The broad effects of the functional IL-10 promoter-592 polymorphism: modulation of IL-10, TIMP-3, and OPG expression and their association with periodontal disease outcome. J Leukoc Biol. 2008;84:1565–1573.
    1. Cole KL, Seymour GJ, Powell RN. Phenotypic and functional analysis of T cells extracted from chronically inflamed human periodontal tissues. J Periodontol. 1987;58:569–573.
    1. Cook DN, Pisetsky DS, Schwartz DA. Toll-like receptors in the pathogenesis of human disease. Nat Immunol. 2004;5:975–979.
    1. Cutz E, Chan W, Track NS, Goth A, Said SI. Release of vasoactive intestinal polypeptide in mast cells by histamine liberators. Nature. 1978;275:661–662.
    1. D’Ambrosio D, Iellem A, Bonecchi R, Mazzeo D, Sozzani S, Mantovani A, Sinigaglia F. Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells. J Immunol. 1998;161:5111–5115.
    1. de Hoon JN, Pickkers P, Smits P, Struijker-Boudier HA, Van Bortel LM. Calcitonin gene-related peptide: exploring its vasodilating mechanism of action in humans. Clin Pharmacol Ther. 2003;73:312–321.
    1. de Waal Malefyt R, Figdor CG, Huijbens R, Mohan-Peterson S, Bennett B, Culpepper J, Dang W, Zurawski G, de Vries JE. Effects of IL-13 on phenotype, cytokine production, and cytotoxic function of human monocytes. Comparison with IL-4 and modulation by IFN-gamma or IL-10. J Immunol. 1993;151:6370–6381.
    1. de Waal Malefyt R, Yssel H, de Vries JE. Direct effects of IL-10 on subsets of human CD4+ T cell clones and resting T cells. Specific inhibition of IL-2 production and proliferation. J Immunol. 1993;150:4754–4765.
    1. Dietrich JW, Goodson JM, Raisz LG. Stimulation of bone resorption by various prostaglandins in organ culture. Prostaglandins. 1975;10:231–240.
    1. Dinarello CA. Proinflammatory cytokines. Chest. 2000;118:503–508.
    1. Dipietro LA, Reintjes MG, Low QE, Levi B, Gamelli RL. Modulation of macrophage recruitment into wounds by monocyte chemoattractant protein-1. Wound Repair Regen. 2001;9:28–33.
    1. Donnelly RP, Fenton MJ, Finbloom DS, Gerrard TL. Differential regulation of IL-1 production in human monocytes by IFN-gamma and IL-4. J Immunol. 1990;145:569–575.
    1. Dutzan N, Gamonal J, Silva A, Sanz M, Vernal R. Overexpression of forkhead box p3 and its association with receptor activator of nuclear factor-kappa B ligand, interleukin (IL)-17, IL-10 and transforming growth factor-beta during the progression of chronic periodontitis. J Clin Periodontol. 2009;36:396–403.
    1. Dutzan N, Vernal R, Hernandez M, Dezerega A, Rivera O, Silva N, Aguillon JC, Puente J, Pozo P, Gamonal J. Levels of interferon-gamma and transcription factor T-bet in progressive periodontal lesions in patients with chronic periodontitis. J Periodontol. 2009;80:290–296.
    1. Egeblad M, Werb Z. New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 2002;2:161–174.
    1. Esche C, Stellato C, Beck LA. Chemokines: key players in innate and adaptive immunity. J Invest Dermatol. 2005;125:615–628.
    1. Essner R, Rhoades K, McBride WH, Morton DL, Economou JS. IL-4 down-regulates IL-1 and TNF gene expression in human monocytes. J Immunol. 1989;142:3857–3861.
    1. Fazilleau N, Mark L, McHeyzer-Williams LJ, McHeyzer-Williams MG. Follicular helper T cells: lineage and location. Immunity. 2009;30:324–335.
    1. Fiorellini JP, Ishikawa SO, Kim DM. Gingival inflammation. In: Carranza FA, editor. Clinical periodontology. Philadelphia: Elsevier Saunders; 2006. pp. 355–361.
    1. Fiorentino DF, Zlotnik A, Vieira P, Mosmann TR, Howard M, Moore KW, O’Garra A. IL-10 acts on the antigen-presenting cell to inhibit cytokine production by Th1 cells. J Immunol. 1991;146:3444–3451.
    1. Fiorucci S, Distrutti E. Role of PAR2 in pain and inflammation. Trends Pharmacol Sci. 2002;23:153–155.
    1. Firth JD, Putnins EE, Larjava H, Uitto VJ. Bacterial phospholipase C upregulates matrix metalloproteinase expression by cultured epithelial cells. Infect Immun. 1997;65:4931–4936.
    1. Flemmig TF. Periodontitis. Ann Periodontol. 1999;4:32–38.
    1. Fonseca JE, Santos MJ, Canhao H, Choy E. Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev. 2009;8:538–542.
    1. Ganea D, Delgado M. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as modulators of both innate and adaptive immunity. Crit Rev Oral Biol Med. 2002;13:229–237.
    1. Garlet GP. Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. J Dent Res. 2010;89:1349–1363.
    1. Garlet GP, Cardoso CR, Campanelli AP, Ferreira BR, Avila-Campos MJ, Cunha FQ, Silva JS. 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;147:128–138.
    1. Garlet GP, Cardoso CR, Campanelli AP, Martins W, Jr, Silva JS. Expression of suppressors of cytokine signaling in diseased periodontal tissues: a stop signal for disease progression? J Periodontal Res. 2006;41:580–584.
    1. Garlet GP, Martins W, Jr, Ferreira BR, Milanezi CM, Silva JS. Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease. J Periodontal Res. 2003;38:210–217.
    1. Garlet GP, Martins W, Jr, Fonseca BA, Ferreira BR, Silva JS. Matrix metalloproteinases, their physiological inhibitors and osteoclast factors are differentially regulated by the cytokine profile in human periodontal disease. J Clin Periodontol. 2004;31:671–679.
    1. Gemmell E, Carter CL, Hart DN, Drysdale KE, Seymour GJ. Antigen-presenting cells in human periodontal disease tissues. Oral Microbiol Immunol. 2002;17:388–393.
    1. Gemmell E, Carter CL, Seymour GJ. Chemokines in human periodontal disease tissues. Clin Exp Immunol. 2001;125:134–141.
    1. Gemmell E, Marshall RI, Seymour GJ. Cytokines and prostaglandins in immune homeostasis and tissue destruction in periodontal disease. Periodontol 2000. 1997;14:112–143.
    1. Gemmell E, Yamazaki K, Seymour GJ. Destructive periodontitis lesions are determined by the nature of the lymphocytic response. Crit Rev Oral Biol Med. 2002;13:17–34.
    1. Geppetti P. Sensory neuropeptide release by bradykinin: mechanisms and pathophysiological implications. Regul Pept. 1993;47:1–23.
    1. Giannopoulou C, Kamma JJ, Mombelli A. Effect of inflammation, smoking and stress on gingival crevicular fluid cytokine level. J Clin Periodontol. 2003;30:145–153.
    1. Goodson JM, Dewhirst FE, Brunetti A. Prostaglandin E2 levels and human periodontal disease. Prostaglandins. 1974;6:81–85.
    1. Grassi F, Cristino S, Toneguzzi S, Piacentini A, Facchini A, Lisignoli G. CXCL12 chemokine up-regulates bone resorption and MMP-9 release by human osteoclasts: CXCL12 levels are increased in synovial and bone tissue of rheumatoid arthritis patients. J Cell Physiol. 2004;199:244–251.
    1. Grassi F, Piacentini A, Cristino S, Toneguzzi S, Cavallo C, Facchini A, Lisignoli G. Human osteoclasts express different CXC chemokines depending on cell culture substrate: molecular and immunocytochemical evidence of high levels of CXCL10 and CXCL12. Histochem Cell Biol. 2003;120:391–400.
    1. Graves DT, Cochran D. The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. J Periodontol. 2003;74:391–401.
    1. Graves DT, Fine D, Teng YT, Van Dyke TE, Hajishengallis G. The use of rodent models to investigate host-bacteria interactions related to periodontal diseases. J Clin Periodontol. 2008;35:89–105.
    1. Gu L, Tseng S, Horner RM, Tam C, Loda M, Rollins BJ. Control of Th2 polarization by the chemokine monocyte chemoattractant protein-1. Nature. 2000;404:407–411.
    1. Hanada T, Yoshimura A. Regulation of cytokine signaling and inflammation. Cytokine Growth Factor Rev. 2002;13:413–421.
    1. Hanazawa S, Kawata Y, Takeshita A, Kumada H, Okithu M, Tanaka S, Yamamoto Y, Masuda T, Umemoto T, Kitano S. 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. 1993;61:5219–5224.
    1. Hanemaaijer R, Sorsa T, Konttinen YT, Ding Y, Sutinen M, Visser H, van Hinsbergh VW, Helaakoski T, Kainulainen T, Ronka H, Tschesche H, Salo T. Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor-alpha and doxycycline. J Biol Chem. 1997;272:31504–31509.
    1. Hanioka T, Takaya K, Matsumori Y, Matsuse R, Shizukuishi S. Relationship of the substance P to indicators of host response in human gingival crevicular fluid. J Clin Periodontol. 2000;27:262–266.
    1. Harrell JC, Stein SH. Prostaglandin E2 regulates gingival mononuclear cell immunoglobulin production. J Periodontol. 1995;66:222–227.
    1. Hartung HP, Wolters K, Toyka KV. Substance P: binding properties and studies on cellular responses in guinea pig macrophages. J Immunol. 1986;136:3856–3863.
    1. Hasturk H, Kantarci A, Goguet-Surmenian E, Blackwood A, Andry C, Serhan CN, Van Dyke TE. Resolvin E1 regulates inflammation at the cellular and tissue level and restores tissue homeostasis in vivo. J Immunol. 2007;179:7021–7029.
    1. Hatakeyama J, Tamai R, Sugiyama A, Akashi S, Sugawara S, Takada H. Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14 / toll-like receptor system. Oral Microbiol Immunol. 2003;18:14–23.
    1. Hayashi S, Yamada T, Tsuneto M, Yamane T, Takahashi M, Shultz LD, Yamazaki H. Distinct osteoclast precursors in the bone marrow and extramedullary organs characterized by responsiveness to toll-like receptor ligands and TNF-alpha. J Immunol. 2003;171:5130–5139.
    1. Henderson B, Nair SP, Ward JM, Wilson M. Molecular pathogenicity of the oral opportunistic pathogen Actinobacillus actinomycetemcomitans. Annu Rev Microbiol. 2003;57:29–55.
    1. Trowbridge HO, Emling RC. Inflammation: a review of the process. Illinois: Quintessence Publishing Co, Inc.; 1997. Introduction; pp. IX–X.
    1. Hirschfeld M, Weis JJ, Toshchakov V, Salkowski CA, Cody MJ, Ward DC, Qureshi N, Michalek SM, Vogel SN. Signaling by toll-like receptor 2 and 4 agonists results in differential gene expression in murine macrophages. Infect Immun. 2001;69:1477–1482.
    1. Hofbauer LC, Schoppet M. Clinical implications of the osteoprotegerin / RANKL / RANK system for bone and vascular diseases. JAMA. 2004;292:490–495.
    1. Honda T, Domon H, Okui T, Kajita K, Amanuma R, Yamazaki K. Balance of inflammatory response in stable gingivitis and progressive periodontitis lesions. Clin Exp Immunol. 2006;144:35–40.
    1. Honore P, Luger NM, Sabino MA, Schwei MJ, Rogers SD, Mach DB, O’Keefe PF, Ramnaraine ML, Clohisy DR, Mantyh PW. Osteoprotegerin blocks bone cancer-induced skeletal destruction, skeletal pain and pain-related neurochemical reorganization of the spinal cord. Nat Med. 2000;6:521–528.
    1. Hoyle CHV. Neuropeptides, essential data. Chichester, UK: John Wiley & and Sons Ltd; 1996.
    1. Hsu H, Lacey DL, Dunstan CR, Solovyev I, Colombero A, Timms E, Tan HL, Elliott G, Kelley MJ, Sarosi I, Wang L, Xia XZ, Elliott R, Chiu L, Black T, Scully S, Capparelli C, Morony S, Shimamoto G, Bass MB, Boyle WJ. Tumor necrosis factor receptor family member RANK mediates osteoclast differentiation and activation induced by osteoprotegerin ligand. Proc Natl Acad Sci USA. 1999;96:3540–3545.
    1. Hua XY, Chen P, Fox A, Myers RR. Involvement of cytokines in lipopolysaccharide-induced facilitation of CGRP release from capsaicin-sensitive nerves in the trachea: studies with interleukin-1beta and tumor necrosis factor-alpha. J Neurosci. 1996;16:4742–4748.
    1. Ihn H, Yamane K, Asano Y, Kubo M, Tamaki K. IL-4 up-regulates the expression of tissue inhibitor of metalloproteinase-2 in dermal fibroblasts via the p38 mitogen-activated protein kinase dependent pathway. J Immunol. 2002;168:1895–1902.
    1. Iino Y, Hopps RM. The bone-resorbing activities in tissue culture of lipopolysaccharides from the bacteria Actinobacillus actinomycetemcomitans, Bacteroides gingivalis and Capnocytophaga ochracea isolated from human mouths. Arch Oral Biol. 1984;29:59–63.
    1. Inohara N, Nunez G. NODS: intracellular proteins involved in inflammation and apoptosis. Nat Rev Immunol. 2003;3:371–382.
    1. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987–995.
    1. Janeway CA, Jr, Medzhitov R. Innate immune recognition. Annu Rev Immunol. 2002;20:197–216.
    1. Jarrossay D, Napolitani G, Colonna M, Sallusto F, Lanzavecchia A. Specialization and complementarity in microbial molecule recognition by human myeloid and plasmacytoid dendritic cells. Eur J Immunol. 2001;31:3388–3393.
    1. Fiorellini JP, Ishikawa SO, Kim DM. Clinical features of gingivitis. In: Carranza FA, editor. Clinical periodontology. Philadelphia: Saunders Elsevier; 2006. pp. 362–372.
    1. Jovanovic DV, Di Battista JA, Martel-Pelletier J, Jolicoeur FC, He Y, Zhang M, Mineau F, Pelletier JP. IL-17 stimulates the production and expression of proinflammatory cytokines, IL-beta and TNF-alpha, by human macrophages. J Immunol. 1998;160:3513–3521.
    1. Kabashima H, Yoneda M, Nagata K, Hirofuji T, Ishihara Y, Yamashita M, Maeda K. The presence of chemokine receptor (CCR5, CXCR3, CCR3)-positive cells and chemokine (MCP1, MIP-1alpha, MIP-1beta, IP-10)-positive cells in human periapical granulomas. Cytokine. 2001;16:62–66.
    1. Kabashima H, Yoneda M, Nagata K, Hirofuji T, Maeda K. The presence of chemokine (MCP-1, MIP-1alpha, MIP-1beta, IP-10, RANTES)-positive cells and chemokine receptor (CCR5, CXCR3)-positive cells in inflamed human gingival tissues. Cytokine. 2002;20:70–77.
    1. Kadowaki N, Ho S, Antonenko S, Malefyt RW, Kastelein RA, Bazan F, Liu YJ. Subsets of human dendritic cell precursors express different toll-like receptors and respond to different microbial antigens. J Exp Med. 2001;194:863–869.
    1. Kagnoff MF, Eckmann L. Epithelial cells as sensors for microbial infection. J Clin Invest. 1997;100:6–10.
    1. Kahari VM, Saarialho-Kere U. Matrix metalloproteinases in skin. Exp Dermatol. 1997;6:199–213.
    1. Kahari VM, Saarialho-Kere U. Matrix metalloproteinases and their inhibitors in tumour growth and invasion. Ann Med. 1999;31:34–45.
    1. Kaisho T, Akira S. Toll-like receptors as adjuvant receptors. Biochim Biophys Acta. 2002;1589:1–13.
    1. Kantarci A, Oyaizu K, Van Dyke TE. Neutrophil-mediated tissue injury in periodontal disease pathogenesis: findings from localized aggressive periodontitis. J Periodontol. 2003;74:66–75.
    1. Kantarci A, Van Dyke TE. Lipoxins in chronic inflammation. Crit Rev Oral Biol Med. 2003;14:4–12.
    1. Kaplan G, Luster AD, Hancock G, Cohn ZA. The expression of a gamma interferon-induced protein (IP-10) in delayed immune responses in human skin. J Exp Med. 1987;166:1098–1108.
    1. Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux NY, Goncalves RB, Valverde P, Dibart S, Li YP, Miranda LA, Ernst CW, Izumi Y, Taubman MA. B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 2006;169:987–998.
    1. Kelso A. Th1 and Th2 subsets: paradigms lost? Immunol Today. 1995;16:374–379.
    1. Kessler JA, Freidin MM, Kalberg C, Chandross KJ. Cytokines regulate substance P expression in sympathetic neurons. Regul Pept. 1993;46:70–75.
    1. Kiili M, Cox SW, Chen HY, Wahlgren J, Maisi P, Eley BM, Salo T, Sorsa T. Collagenase-2 (MMP-8) and collagenase-3 (MMP-13) in adult periodontitis: molecular forms and levels in gingival crevicular fluid and immunolocalisation in gingival tissue. J Clin Periodontol. 2002;29:224–232.
    1. Kim MS, Day CJ, Selinger CI, Magno CL, Stephens SR, Morrison NA. MCP-1-induced human osteoclast-like cells are tartrate-resistant acid phosphatase, NFATC1, and calcitonin receptor-positive but require receptor activator of NFkappaB ligand for bone resorption. J Biol Chem. 2006;281:1274–1285.
    1. Kim MS, Magno CL, Day CJ, Morrison NA. Induction of chemokines and chemokine receptors CCR2b and CCR4 in authentic human osteoclasts differentiated with rankl and osteoclast like cells differentiated by MCP-1 and RANTES. J Cell Biochem. 2006;97:512–518.
    1. Kindle L, Rothe L, Kriss M, Osdoby P, Collin-Osdoby P. Human microvascular endothelial cell activation by IL-1 and TNF-alpha stimulates the adhesion and transendothelial migration of circulating human CD14+ monocytes that develop with RANKL into functional osteoclasts. J Bone Miner Res. 2006;21:193–206.
    1. King C, Tangye SG, Mackay CR. T follicular helper (TFH) cells in normal and dysregulated immune responses. Annu Rev Immunol. 2008;26:741–766.
    1. Klausen B, Hougen HP, Fiehn NE. Increased periodontal bone loss in temporarily B lymphocyte-deficient rats. J Periodontal Res. 1989;24:384–390.
    1. Knauper V, Cowell S, Smith B, Lopez-Otin C, O’Shea M, Morris H, Zardi L, Murphy G. The role of the C-terminal domain of human collagenase-3 (MMP-13) in the activation of procollagenase-3, substrate specificity, and tissue inhibitor of metalloproteinase interaction. J Biol Chem. 1997;272:7608–7616.
    1. Kobayashi M, Fitz L, Ryan M, Hewick RM, Clark SC, Chan S, Loudon R, Sherman F, Perussia B, Trinchieri G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med. 1989;170:827–845.
    1. Kong YY, Feige U, Sarosi I, Bolon B, Tafuri A, Morony S, Capparelli C, Li J, Elliott R, McCabe S, Wong T, Campagnuolo G, Moran E, Bogoch ER, Van G, Nguyen LT, Ohashi PS, Lacey DL, Fish E, Boyle WJ, Penninger JM. Activated T cells regulate bone loss and joint destruction in adjuvant arthritis through osteoprotegerin ligand. Nature. 1999;402:304–309.
    1. Konttinen Y, Imai S, Suda A. Neuropeptides and the puzzle of bone remodeling. State of the art. Acta Orthop Scand. 1996;67:632–639.
    1. Konttinen YT, Salo T, Hanemaaijer R, Valleala H, Sorsa T, Sutinen M, Ceponis A, Xu JW, Santavirta S, Teronen O, Lopez-Otin C. Collagenase-3 (MMP-13) and its activators in rheumatoid arthritis: localization in the pannus-hard tissue junction and inhibition by alendronate. Matrix Biol. 1999;18:401–412.
    1. Krutzik SR, Modlin RL. The role of toll-like receptors in combating mycobacteria. Semin Immunol. 2004;16:35–41.
    1. Kvinnsland I, Heyeraas KJ. Effect of traumatic occlusion on CGRP and SP immunoreactive nerve fibre morphology in rat molar pulp and periodontium. Histochemistry. 1992;97:111–120.
    1. Kwak HB, Lee SW, Jin HM, Ha H, Lee SH, Takeshita S, Tanaka S, Kim HM, Kim HH, Lee ZH. Monokine induced by interferon-gamma is induced by receptor activator of nuclear factor kappa B ligand and is involved in osteoclast adhesion and migration. Blood. 2005;105:2963–2969.
    1. Kwan Tat S, Padrines M, Theoleyre S, Heymann D, Fortun Y. IL-6, RANKL, TNF-alpha / IL-1: interrelations in bone resorption pathophysiology. Cytokine Growth Factor Rev. 2004;15:49–60.
    1. Lacey DL, Timms E, Tan HL, Kelley MJ, Dunstan CR, Burgess T, Elliott R, Colombero A, Elliott G, Scully S, Hsu H, Sullivan J, Hawkins N, Davy E, Capparelli C, Eli A, Qian YX, Kaufman S, Sarosi I, Shalhoub V, Senaldi G, Guo J, Delaney J, Boyle WJ. Osteoprotegerin ligand is a cytokine that regulates osteoclast differentiation and activation. Cell. 1998;93:165–176.
    1. Lai JP, Douglas SD, Ho WZ. Human lymphocytes express substance P and its receptor. J Neuroimmunol. 1998;86:80–86.
    1. Lambrecht BN, Germonpre PR, Everaert EG, Carro-Muino I, De Veerman M, de Felipe C, Hunt SP, Thielemans K, Joos GF, Pauwels RA. Endogenously produced substance P contributes to lymphocyte proliferation induced by dendritic cells and direct TCR ligation. Eur J Immunol. 1999;29:3815–3825.
    1. Lamont AG, Adorini L. IL-12: a key cytokine in immune regulation. Immunol Today. 1996;17:214–217.
    1. Lappin DF, MacLeod CP, Kerr A, Mitchell T, Kinane DF. Anti-inflammatory cytokine IL-10 and T cell cytokine profile in periodontitis granulation tissue. Clin Exp Immunol. 2001;123:294–300.
    1. Lean JM, Murphy C, Fuller K, Chambers TJ. CCL9 / MIP-1gamma and its receptor CCR1 are the major chemokine ligand / receptor species expressed by osteoclasts. J Cell Biochem. 2002;87:386–393.
    1. Lee W, Aitken S, Sodek J, McCulloch CA. Evidence of a direct relationship between neutrophil collagenase activity and periodontal tissue destruction in vivo: role of active enzyme in human periodontitis. J Periodontal Res. 1995;30:23–33.
    1. Lembeck F, Donnerer J, Tsuchiya M, Nagahisa A. The non-peptide tachykinin antagonist, CP-96,345, is a potent inhibitor of neurogenic inflammation. Br J Pharmacol. 1992;105:527–530.
    1. Levite M. Neuropeptides, by direct interaction with T cells, induce cytokine secretion and break the commitment to a distinct T helper phenotype. Proc Natl Acad Sci USA. 1998;95:12544–12549.
    1. Levy BD, Clish CB, Schmidt B, Gronert K, Serhan CN. Lipid mediator class switching during acute inflammation: signals in resolution. Nat Immunol. 2001;2:612–619.
    1. Lewis RA. Interactions of eicosanoids and cytokines in immune regulation. Adv Prostaglandin Thromboxane Leukot Res. 1990;20:170–178.
    1. Lieb K, Fiebich BL, Busse-Grawitz M, Hull M, Berger M, Bauer J. Effects of substance P and selected other neuropeptides on the synthesis of interleukin-1 beta and interleukin-6 in human monocytes: a re-examination. J Neuroimmunol. 1996;67:77–81.
    1. Linden GJ, McKinnell J, Shaw C, Lundy FT. Substance P and neurokinin A in gingival crevicular fluid in periodontal health and disease. J Clin Periodontol. 1997;24:799–803.
    1. Linden GJ, Mullally BH, Burden DJ, Lamey PJ, Shaw C, Ardill J, Lundy FT. Changes in vasoactive intestinal peptide in gingival crevicular fluid in response to periodontal treatment. J Clin Periodontol. 2002;29:484–489.
    1. Lisignoli G, Cristino S, Toneguzzi S, Grassi F, Piacentini A, Cavallo C, Facchini A, Mariani E. IL1beta and TNFalpha differently modulate CXCL13 chemokine in stromal cells and osteoblasts isolated from osteoarthritis patients: evidence of changes associated to cell maturation. Exp Gerontol. 2004;39:659–665.
    1. Lisignoli G, Toneguzzi S, Piacentini A, Cristino S, Grassi F, Cavallo C, Facchini A. CXCL12 (SDF-1) and CXCL13 (BCA-1) chemokines significantly induce proliferation and collagen type I expression in osteoblasts from osteoarthritis patients. J Cell Physiol. 2006;206:78–85.
    1. Liu YC, Lerner UH, Teng YT. Cytokine responses against periodontal infection: protective and destructive roles. Periodontol 2000. 2010;52:163–206.
    1. Loetscher P, Pellegrino A, Gong JH, Mattioli I, Loetscher M, Bardi G, Baggiolini M, Clark-Lewis I. The ligands of cxc chemokine receptor 3, i-tac, mig, and ip10, are natural antagonists for CCR3. J Biol Chem. 2001;276:2986–2991.
    1. Loetscher P, Uguccioni M, Bordoli L, Baggiolini M, Moser B, Chizzolini C, Dayer JM. Ccr5 is characteristic of th1 lymphocytes. Nature. 1998;391:344–345.
    1. Loning T, Albers HK, Lisboa BP, Burkhardt A, Caselitz J. Prostaglandin e and the local immune response in chronic periodontal disease. Immunohistochemical and radioimmunological observations. J Periodontal Res. 1980;15:525–535.
    1. Low QE, Drugea IA, Duffner LA, Quinn DG, Cook DN, Rollins BJ, Kovacs EJ, DiPietro LA. Wound healing in MIP-1alpha −/−) and MCP-1 −/−) mice. Am J Pathol. 2001;159:457–463.
    1. Lundy FT, Linden GJ. Neuropeptides and neurogenic mechanisms in oral and periodontal inflammation. Crit Rev Oral Biol Med. 2004;15:82–98.
    1. Lundy FT, Mullally BH, Burden DJ, Lamey PJ, Shaw C, Linden GJ. Changes in substance P and neurokinin A in gingival crevicular fluid in response to periodontal treatment. J Clin Periodontol. 2000;27:526–530.
    1. Lundy FT, Shaw C, McKinnell J, Lamey PJ, Linden GJ. Calcitonin gene-related peptide in gingival crevicular fluid in periodontal health and disease. J Clin Periodontol. 1999;26:212–216.
    1. Luthman J, Johansson O, Ahlstrom U, Kvint S. Immunohistochemical studies of the neurochemical markers, CGRP, enkephalin, galanin, gamma-MSH, NPY, PHI, proctolin, PTH, somatostatin, SP, VIP, tyrosine hydroxylase and neurofilament in nerves and cells of the human attached gingiva. Arch Oral Biol. 1988;33:149–158.
    1. Novak JM, Novak KF. Chronic periodontitis. In: Carranza FA, editor. Clinical periodontology. Philadelphia: Saunders Elsevier; 2006. pp. 494–499.
    1. MacDonald KP, Rowe V, Bofinger HM, Thomas R, Sasmono T, Hume DA, Hill GR. The colony-stimulating factor 1 receptor is expressed on dendritic cells during differentiation and regulates their expansion. J Immunol. 2005;175:1399–1405.
    1. Maddox JF, Hachicha M, Takano T, Petasis NA, Fokin VV, Serhan CN. Lipoxin A4 stable analogs are potent mimetics that stimulate human monocytes and THP-1 cells via a G-protein-linked lipoxin A4 receptor. J Biol Chem. 1997;272:6972–6978.
    1. Maddox JF, Serhan CN. Lipoxin A4 and B4 are potent stimuli for human monocyte migration and adhesion: selective inactivation by dehydrogenation and reduction. J Exp Med. 1996;183:137–146.
    1. Mahamed DA, Marleau A, Alnaeeli M, Singh B, Zhang X, Penninger JM, Teng YT. G(−) anaerobes-reactive CD4+ T-cells trigger RANKL-mediated enhanced alveolar bone loss in diabetic NOD mice. Diabetes. 2005;54:1477–1486.
    1. Makela M, Larjava H, Pirila E, Maisi P, Salo T, Sorsa T, Uitto VJ. Matrix metalloproteinase 2 (gelatinase A) is related to migration of keratinocytes. Exp Cell Res. 1999;251:67–78.
    1. Ryan ME, Preshaw PM. Host modulation. In: Carranza FA, editor. Clinical periodontology. Philadelphia: Saunders Elsevier; 2006. pp. 275–283.
    1. Marriott I, Bost KL. Substance P diminishes lipopolysaccharide and interferon-gamma-induced TGF-beta 1 production by cultured murine macrophages. Cell Immunol. 1998;183:113–120.
    1. Martin TJ, Sims NA. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med. 2005;11:76–81.
    1. Mathur A, Michalowicz B, Castillo M, Aeppli D. Interleukin-1 alpha, interleukin-8 and interferon-alpha levels in gingival crevicular fluid. J Periodontal Res. 1996;31:489–495.
    1. McCawley LJ, Matrisian LM. Matrix metalloproteinases: they’re not just for matrix anymore! Curr Opin Cell Biol. 2001;13:534–540.
    1. McGillis JP, Humphreys S, Reid S. Characterization of functional calcitonin gene-related peptide receptors on rat lymphocytes. J Immunol. 1991;147:3482–3489.
    1. Medzhitov R, Janeway CA., Jr Innate immunity: the virtues of a nonclonal system of recognition. Cell. 1997;91:295–298.
    1. Mendieta CF, Reeve CM, Romero JC. Biosynthesis of prostaglandins in gingiva of patients with chronic periodontitis. J Periodontol. 1985;56:44–47.
    1. Metwali A, Blum AM, Ferraris L, Klein JS, Fiocchi C, Weinstock JV. Eosinophils within the healthy or inflamed human intestine produce substance P and vasoactive intestinal peptide. J Neuroimmunol. 1994;52:69–78.
    1. Mizuno A, Amizuka N, Irie K, Murakami A, Fujise N, Kanno T, Sato Y, Nakagawa N, Yasuda H, Mochizuki S, Gomibuchi T, Yano K, Shima N, Washida N, Tsuda E, Morinaga T, Higashio K, Ozawa H. Severe osteoporosis in mice lacking osteoclastogenesis inhibitory factor / osteoprotegerin. Biochem Biophys Res Commun. 1998;247:610–615.
    1. Modlin RL, Nutman TB. Type 2 cytokines and negative immune regulation in human infections. Curr Opin Immunol. 1993;5:511–517.
    1. Moser B, Wolf M, Walz A, Loetscher P. Chemokines: multiple levels of leukocyte migration control. Trends Immunol. 2004;25:75–84.
    1. Murphy KM, Reiner SL. The lineage decisions of helper T cells. Nat Rev Immunol. 2002;2:933–944.
    1. Musacchio E, Valvason C, Botsios C, Ostuni F, Furlan A, Ramonda R, Modesti V, Sartori L, Punzi L. The tumor necrosis factor-{alpha}-blocking agent infliximab inhibits interleukin 1beta (IL-1beta) and IL-6 gene expression in human osteoblastic cells. J Rheumatol. 2009;36:1575–1579.
    1. Nagase H. Activation mechanisms of matrix metalloproteinases. Biol Chem. 1997;378:151–160.
    1. Nakajima T, Ueki-Maruyama K, Oda T, Ohsawa Y, Ito H, Seymour GJ, Yamazaki K. Regulatory T-cells infiltrate periodontal disease tissues. J Dent Res. 2005;84:639–643.
    1. Naundorf S, Schroder M, Hoflich C, Suman N, Volk HD, Grutz G. IL-10 interferes directly with TCR-induced IFN-gamma but not IL-17 production in memory T cells. Eur J Immunol. 2009;39:1066–1077.
    1. Nong YH, Titus RG, Ribeiro JM, Remold HG. Peptides encoded by the calcitonin gene inhibit macrophage function. J Immunol. 1989;143:45–49.
    1. O’Dorisio MS, O’Dorisio TM, Cataland S, Balcerzak SP. Vasoactive intestinal polypeptide as a biochemical marker for polymorphonuclear leukocytes. J Lab Clin Med. 1980;96:666–672.
    1. O’Garra A. Interleukins and the immune system 2. Lancet. 1989;1:1003–1005.
    1. Ohyama H, Kato-Kogoe N, Kuhara A, Nishimura F, Nakasho K, Yamanegi K, Yamada N, Hata M, Yamane J, Terada N. The involvement of IL-23 and the Th17 pathway in periodontitis. J Dent Res. 2009;88:633–638.
    1. Okada H, Murakami S. Cytokine expression in periodontal health and disease. Crit Rev Oral Biol Med. 1998;9:248–266.
    1. Okada N, Kobayashi M, Mugikura K, Okamatsu Y, Hanazawa S, Kitano S, Hasegawa K. Interleukin-6 production in human fibroblasts derived from periodontal tissues is differentially regulated by cytokines and a glucocorticoid. J Periodontal Res. 1997;32:559–569.
    1. Okamatsu Y, Kim D, Battaglino R, Sasaki H, Spate U, Stashenko P. MIP-1 gamma promotes receptor-activator- of-NF-kappa-B-ligand-induced osteoclast formation and survival. J Immunol. 2004;173:2084–2090.
    1. Opree A, Kress M. Involvement of the proinflammatory cytokines tumor necrosis factor-alpha, IL-1 beta, and IL-6 but not IL-8 in the development of heat hyperalgesia: effects on heat-evoked calcitonin gene-related peptide release from rat skin. J Neurosci. 2000;20:6289–6293.
    1. Owan I, Ibaraki K. The role of calcitonin gene-related peptide (CGRP) in macrophages: the presence of functional receptors and effects on proliferation and differentiation into osteoclast-like cells. Bone Miner. 1994;24:151–164.
    1. Page RC, Schroeder HE. Pathogenesis of inflammatory periodontal disease. A summary of current work. Lab Invest. 1976;34:235–249.
    1. The American Academy of Periodontology. The pathogenesis of periodontal diseases. J Periodontol. 1999;70:457–470.
    1. Payne JB, Reinhardt RA, Masada MP, DuBois LM, Allison AC. Gingival crevicular fluid IL-8: correlation with local IL-1 beta levels and patient estrogen status. J Periodontal Res. 1993;28:451–453.
    1. Perussia B, Chan SH, D’Andrea A, Tsuji K, Santoli D, Pospisil M, Young D, Wolf SF, Trinchieri G. Natural killer (NK) cell stimulatory factor or IL-12 has differential effects on the proliferation of TCR-alpha beta+, TCR-gamma delta+ T lymphocytes, and NK cells. J Immunol. 1992;149:3495–3502.
    1. Peschon JJ, Torrance DS, Stocking KL, Glaccum MB, Otten C, Willis CR, Charrier K, Morrissey PJ, Ware CB, Mohler KM. TNF receptor-deficient mice reveal divergent roles for p55 and p75 in several models of inflammation. J Immunol. 1998;160:943–952.
    1. Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher PB. Interleukin-10 and related cytokines and receptors. Annu Rev Immunol. 2004;22:929–979.
    1. Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366:1809–1820.
    1. Pozo D, Delgado M, Martinez M, Guerrero JM, Leceta J, Gomariz RP, Calvo JR. Immunobiology of vasoactive intestinal peptide (VIP) Immunol Today. 2000;21:7–11.
    1. Putnins EE, Firth JD, Uitto VJ. Stimulation of collagenase (matrix metalloproteinase-1) synthesis in histiotypic epithelial cell culture by heparin is enhanced by keratinocyte growth factor. Matrix Biol. 1996;15:21–29.
    1. Quesniaux V, Fremond C, Jacobs M, Parida S, Nicolle D, Yeremeev V, Bihl F, Erard F, Botha T, Drennan M, Soler MN, Le Bert M, Schnyder B, Ryffel B. Toll-like receptor pathways in the immune responses to mycobacteria. Microbes Infect. 2004;6:946–959.
    1. Richards D, Rutherford RB. The effects of interleukin 1 on collagenolytic activity and prostaglandin-E secretion by human periodontal-ligament and gingival fibroblast. Arch Oral Biol. 1988;33:237–243.
    1. Rietschel ET, Brade H. Bacterial endotoxins. Sci Am. 1992;267:54–61.
    1. Rodan GA, Martin TJ. Role of osteoblasts in hormonal control of bone resorption–a hypothesis. Calcif Tissue Int. 1981;33:349–351.
    1. Rosa FM, Mellows M. Effect of gamma interferon on MHC antigens. Immunol Today. 1984;9:261–262.
    1. Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol. 2000;18:217–242.
    1. Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol. 2004;22:891–928.
    1. Rousset F, Garcia E, Defrance T, Peronne C, Vezzio N, Hsu DH, Kastelein R, Moore KW, Banchereau J. Interleukin 10 is a potent growth and differentiation factor for activated human B lymphocytes. Proc Natl Acad Sci USA. 1992;89:1890–1893.
    1. Saarialho-Kere UK. Patterns of matrix metalloproteinase and TIMP expression in chronic ulcers. Arch Dermatol Res. 1998;290(Suppl):S47–S54.
    1. Saidenberg-Kermanac’h N, Bessis N, Lemeiter D, de Vernejoul MC, Boissier MC, Cohen-Solal M. Interleukin-4 cellular gene therapy and osteoprotegerin decrease inflammation-associated bone resorption in collagen-induced arthritis. J Clin Immunol. 2004;24:370–378.
    1. Saito S, Rosol TJ, Saito M, Ngan PW, Shanfeld J, Davidovitch Z. Bone-resorbing activity and prostaglandin E produced by human periodontal ligament cells in vitro. J Bone Miner Res. 1990;5:1013–1018.
    1. Saito S, Saito M, Ngan P, Lanese R, Shanfeld J, Davidovitch Z. Effects of parathyroid hormone and cytokines on prostaglandin E synthesis and bone resorption by human periodontal ligament fibroblasts. Arch Oral Biol. 1990;35:845–855.
    1. Sallusto F, Lanzavecchia A. Heterogeneity of CD4+ memory T cells: functional modules for tailored immunity. Eur J Immunol. 2009;39:2076–2082.
    1. Sallusto F, Lanzavecchia A, Mackay CR. Chemokines and chemokine receptors in T-cell priming and Th1 / Th2-mediated responses. Immunol Today. 1998;19:568–574.
    1. Sallusto F, Lenig D, Mackay CR, Lanzavecchia A. Flexible programs of chemokine receptor expression on human polarized T helper 1 and 2 lymphocytes. J Exp Med. 1998;187:875–883.
    1. Sato N, Takahashi N, Suda K, Nakamura M, Yamaki M, Ninomiya T, Kobayashi Y, Takada H, Shibata K, Yamamoto M, Takeda K, Akira S, Noguchi T, Udagawa N. MyD88 but not TRIF is essential for osteoclastogenesis induced by lipopolysaccharide, diacyl lipopeptide, and IL-1alpha. J Exp Med. 2004;200:601–611.
    1. Schaerli P, Willimann K, Lang AB, Lipp M, Loetscher P, Moser B. CXC chemokine receptor 5 expression defines follicular homing T cells with B cell helper function. J Exp Med. 2000;192:1553–1562.
    1. Schwab JM, Chiang N, Arita M, Serhan CN. Resolvin E1 and protectin D1 activate inflammation-resolution programmes. Nature. 2007;447:869–874.
    1. Serhan CN. A search for endogenous mechanisms of anti-inflammation uncovers novel chemical mediators: missing links to resolution. Histochem Cell Biol. 2004;122:305–321.
    1. Serhan CN, Brain SD, Buckley CD, Gilroy DW, Haslett C, O’Neill LA, Perretti M, Rossi AG, Wallace JL. Resolution of inflammation: state of the art, definitions and terms. FASEB J. 2007;21:325–332.
    1. Serhan CN, Chiang N. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol. 2008;153(Suppl 1):S200–S215.
    1. Serhan CN, Chiang N, Van Dyke TE. Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol. 2008;8:349–361.
    1. Serhan CN, Fiore S, Brezinski DA, Lynch S. Lipoxin A4 metabolism by differentiated HL-60 cells and human monocytes: conversion to novel 15-oxo and dihydro products. Biochemistry. 1993;32:6313–6319.
    1. Serhan CN, Maddox JF, Petasis NA, Akritopoulou-Zanze I, Papayianni A, Brady HR, Colgan SP, Madara JL. Design of lipoxin A4 stable analogs that block transmigration and adhesion of human neutrophils. Biochemistry. 1995;34:14609–14615.
    1. Seymour GJ. Importance of the host response in the periodontium. J Clin Periodontol. 1991;18:421–426.
    1. Seymour GJ, Gemmell E. Cytokines in periodontal disease: where to from here? Acta Odontol Scand. 2001;59:167–173.
    1. Sorsa T, Tjaderhane L, Konttinen YT, Lauhio A, Salo T, Lee HM, Golub LM, Brown DL, Mantyla P. Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Ann Med. 2006;38:306–321.
    1. Steinhoff M, Vergnolle N, Young SH, Tognetto M, Amadesi S, Ennes HS, Trevisani M, Hollenberg MD, Wallace JL, Caughey GH, Mitchell SE, Williams LM, Geppetti P, Mayer EA, Bunnett NW. Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000;6:151–158.
    1. Steinsvoll S, Halstensen TS, Schenck K. Extensive expression of TGF-beta1 in chronically-inflamed periodontal tissue. J Clin Periodontol. 1999;26:366–373.
    1. Suda K, Udagawa N, Sato N, Takami M, Itoh K, Woo JT, Takahashi N, Nagai K. Suppression of osteoprotegerin expression by prostaglandin E2 is crucially involved in lipopolysaccharide-induced osteoclast formation. J Immunol. 2004;172:2504–2510.
    1. Suzuki JB, Risom L, Falkler WA, Jr, Collison C, Bowers G. Effect of periodontal therapy on spontaneous lymphocyte response and neutrophil chemotaxis in localized and generalized juvenile periodontitis patients. J Clin Periodontol. 1985;12:124–134.
    1. Takahashi K, Azuma T, Motohira H, Kinane DF, Kitetsu S. The potential role of interleukin-17 in the immunopathology of periodontal disease. J Clin Periodontol. 2005;32:369–374.
    1. Takashiba S, Takigawa M, Takahashi K, Myokai F, Nishimura F, Chihara T, Kurihara H, Nomura Y, Murayama Y. Interleukin-8 is a major neutrophil chemotactic factor derived from cultured human gingival fibroblasts stimulated with interleukin-1 beta or tumor necrosis factor alpha. Infect Immun. 1992;60:5253–5258.
    1. Takeda K, Kaisho T, Akira S. Toll-like receptors. Annu Rev Immunol. 2003;21:335–376.
    1. Takigawa M, Takashiba S, Myokai F, Takahashi K, Arai H, Kurihara H, Murayama Y. Cytokine-dependent synergistic regulation of interleukin-8 production from human gingival fibroblasts. J Periodontol. 1994;65:1002–1007.
    1. Tanaka S, Takahashi N, Udagawa N, Tamura T, Akatsu T, Stanley ER, Kurokawa T, Suda T. Macrophage colony-stimulating factor is indispensable for both proliferation and differentiation of osteoclast progenitors. J Clin Invest. 1993;91:257–263.
    1. Taubman MA, Kawai T. Involvement of T-lymphocytes in periodontal disease and in direct and indirect induction of bone resorption. Crit Rev Oral Biol Med. 2001;12:125–135.
    1. Taylor AW, Yee DG, Streilein JW. Suppression of nitric oxide generated by inflammatory macrophages by calcitonin gene-related peptide in aqueous humor. Invest Ophthalmol Vis Sci. 1998;39:1372–1378.
    1. Terricabras E, Benjamim C, Godessart N. Drug discovery and chemokine receptor antagonists: Eppur si muove! Autoimmun Rev. 2004;3:550–556.
    1. Tervahartiala T, Pirila E, Ceponis A, Maisi P, Salo T, Tuter G, Kallio P, Tornwall J, Srinivas R, Konttinen YT, Sorsa T. The in vivo expression of the collagenolytic matrix metalloproteinases (MMP-2, -8, -13, and -14) and matrilysin (MMP-7) in adult and localized juvenile periodontitis. J Dent Res. 2000;79:1969–1977.
    1. Theill LE, Boyle WJ, Penninger JM. RANK-l and RANK: T cells, bone loss, and mammalian evolution. Annu Rev Immunol. 2002;20:795–823.
    1. Tracey KJ. The inflammatory reflex. Nature. 2002;420:853–859.
    1. Trinchieri G. Interleukin-12 and its role in the generation of Th1 cells. Immunol Today. 1993;14:335–338.
    1. Trinchieri G, Perussia B. Immune interferon: a pleiotropic lymphokine with multiple effects. Immunol Today. 1985;6:131–136.
    1. Uehara A, Takada H. Functional TLRs and NODs in human gingival fibroblasts. J Dent Res. 2007;86:249–254.
    1. Uitto VJ, Airola K, Vaalamo M, Johansson N, Putnins EE, Firth JD, Salonen J, Lopez-Otin C, Saarialho-Kere U, Kahari VM. Collagenase-3 (matrix metalloproteinase-13) expression is induced in oral mucosal epithelium during chronic inflammation. Am J Pathol. 1998;152:1489–1499.
    1. Uitto VJ, Overall CM, McCulloch C. Proteolytic host cell enzymes in gingival crevice fluid. Periodontol 2000. 2003;31:77–104.
    1. van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9) Crit Rev Biochem Mol Biol. 2002;37:375–536.
    1. Van Dyke TE. Control of inflammation and periodontitis. Periodontol 2000. 2007;45:158–166.
    1. Van Dyke TE. The management of inflammation in periodontal disease. J Periodontol. 2008;79:1601–1608.
    1. Van Dyke TE, Serhan CN. Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. J Dent Res. 2003;82:82–90.
    1. Vergnolle N. Proteinase-activated receptor-2-activating peptides induce leukocyte rolling, adhesion, and extravasation in vivo. J Immunol. 1999;163:5064–5069.
    1. Vernal R, Dutzan N, Chaparro A, Puente J, Antonieta Valenzuela M, Gamonal J. Levels of interleukin-17 in gingival crevicular fluid and in supernatants of cellular cultures of gingival tissue from patients with chronic periodontitis. J Clin Periodontol. 2005;32:383–389.
    1. Visse R, Nagase H. Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res. 2003;92:827–839.
    1. Votta BJ, White JR, Dodds RA, James IE, Connor JR, Lee-Rykaczewski E, Eichman CF, Kumar S, Lark MW, Gowen M. CKbeta-8 [CCL23], a novel CC chemokine, is chemotactic for human osteoclast precursors and is expressed in bone tissues. J Cell Physiol. 2000;183:196–207.
    1. Wahlgren J, Salo T, Teronen O, Luoto H, Sorsa T, Tjaderhane L. Matrix metalloproteinase-8 (MMP-8) in pulpal and periapical inflammation and periapical root-canal exudates. Int Endod J. 2002;35:897–904.
    1. Wajant H, Pfizenmaier K, Scheurich P. Tumor necrosis factor signaling. Cell Death Differ. 2003;10:45–65.
    1. Wang F, Millet I, Bottomly K, Vignery A. Calcitonin gene-related peptide inhibits interleukin 2 production by murine T lymphocytes. J Biol Chem. 1992;267:21052–21057.
    1. Watters TM, Kenny EF, O’Neill LA. Structure, function and regulation of the toll / IL-1 receptor adaptor proteins. Immunol Cell Biol. 2007;85:411–419.
    1. Weaver CT, Hatton RD. Interplay between the Th17 and Treg cell lineages: a (co-)evolutionary perspective. Nat Rev Immunol. 2009;9:883–889.
    1. Wilson CL, Matrisian LM. Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions. Int J Biochem Cell Biol. 1996;28:123–136.
    1. Wingrove JA, DiScipio RG, Chen Z, Potempa J, Travis J, Hugli TE. Activation of complement components C3 and C5 by a cysteine proteinase (gingipain-1) from Porphyromonas (Bacteroides) gingivalis. J Biol Chem. 1992;267:18902–18907.
    1. Wright LM, Maloney W, Yu X, Kindle L, Collin-Osdoby P, Osdoby P. Stromal cell-derived factor-1 binding to its chemokine receptor CXCR4 on precursor cells promotes the chemotactic recruitment, development and survival of human osteoclasts. Bone. 2005;36:840–853.
    1. Yago T, Nanke Y, Ichikawa N, Kobashigawa T, Mogi M, Kamatani N, Kotake S. IL-17 induces osteoclastogenesis from human monocytes alone in the absence of osteoblasts, which is potently inhibited by anti-TNF-alpha antibody: a novel mechanism of osteoclastogenesis by IL-17. J Cell Biochem. 2009;108:947–955.
    1. Yang M, Mailhot G, MacKay CA, Mason-Savas A, Aubin J, Odgren PR. Chemokine and chemokine receptor expression during colony stimulating factor-1-induced osteoclast differentiation in the toothless osteopetrotic rat: a key role for CCL9 (MIP-1gamma) in osteoclastogenesis in vivo and in vitro. Blood. 2006;107:2262–2270.
    1. Yano S, Mentaverri R, Kanuparthi D, Bandyopadhyay S, Rivera A, Brown EM, Chattopadhyay N. Functional expression of beta-chemokine receptors in osteoblasts: role of regulated upon activation, normal T cell expressed and secreted (RANTES) in osteoblasts and regulation of its secretion by osteoblasts and osteoclasts. Endocrinology. 2005;146:2324–2335.
    1. Yasuda H, Shima N, Nakagawa N, Mochizuki SI, Yano K, Fujise N, Sato Y, Goto M, Yamaguchi K, Kuriyama M, Kanno T, Murakami A, Tsuda E, Morinaga T, Higashio K. Identity of osteoclastogenesis inhibitory factor (OCIF) and osteoprotegerin (OPG): a mechanism by which OPG / OCIF inhibits osteoclastogenesis in vitro. Endocrinology. 1998;139:1329–1337.
    1. Yiangou Y, Facer P, Dyer NH, Chan CL, Knowles C, Williams NS, Anand P. Vanilloid receptor 1 immunore-activity in inflamed human bowel. Lancet. 2001;357:1338–1339.
    1. Yoshimura T, Matsushima K, Tanaka S, Robinson EA, Appella E, Oppenheim JJ, Leonard EJ. Purification of a human monocyte-derived neutrophil chemotactic factor that has peptide sequence similarity to other host defense cytokines. Proc Natl Acad Sci USA. 1987;84:9233–9237.
    1. Yu X, Huang Y, Collin-Osdoby P, Osdoby P. CCR1 chemokines promote the chemotactic recruitment, RANKL development, and motility of osteoclasts and are induced by inflammatory cytokines in osteoblasts. J Bone Miner Res. 2004;19:2065–2077.
    1. Yumoto H, Nakae H, Fujinaka K, Ebisu S, Matsuo T. Interleukin-6 (IL-6) and IL-8 are induced in human oral epithelial cells in response to exposure to periodontopathic Eikenella corrodens. Infect Immun. 1999;67:384–394.
    1. Zadeh HH, Nichols FC, Miyasaki KT. The role of the cell-mediated immune response to Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis in periodontitis. Periodontol 2000. 1999;20:239–288.
    1. Zlotnik A, Yoshie O. Chemokines: a new classification system and their role in immunity. Immunity. 2000;12:121–127.
    1. Zou W, Amcheslavsky A, Bar-Shavit Z. CpG oligodeoxynucleotides modulate the osteoclastogenic activity of osteoblasts via toll-like receptor 9. J Biol Chem. 2003;278:16732–16740.
    1. Zurawski G, de Vries JE. Interleukin 13, an interleukin 4-like cytokine that acts on monocytes and B cells, but not on T cells. Immunol Today. 1994;15:19–26.

Source: PubMed

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