Skip to main content Accessibility help

Inflammatory mediators in the pathogenesis of periodontitis

  • Tülay Yucel-Lindberg (a1) and Tove Båge (a1)


Periodontitis is a chronic inflammatory condition of the periodontium involving interactions between bacterial products, numerous cell populations and inflammatory mediators. It is generally accepted that periodontitis is initiated by complex and diverse microbial biofilms which form on the teeth, i.e. dental plaque. Substances released from this biofilm such as lipopolysaccharides, antigens and other virulence factors, gain access to the gingival tissue and initiate an inflammatory and immune response, leading to the activation of host defence cells. As a result of cellular activation, inflammatory mediators, including cytokines, chemokines, arachidonic acid metabolites and proteolytic enzymes collectively contribute to tissue destruction and bone resorption. This review summarises recent studies on the pathogenesis of periodontitis, with the main focus on inflammatory mediators and their role in periodontal disease.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Inflammatory mediators in the pathogenesis of periodontitis
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Inflammatory mediators in the pathogenesis of periodontitis
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Inflammatory mediators in the pathogenesis of periodontitis
      Available formats


The online version of this article is published within an Open Access environment subject to the conditions of the Creative Commons Attribution-NonCommercial-ShareAlike licence . The written permission of Cambridge University Press must be obtained for commercial re-use.

Corresponding author

*Corresponding author: Tülay Yucel-Lindberg, Department of Dental Medicine, Division of Periodontology, Karolinska Institutet, SE-141 04 Huddinge, Sweden. E-mail:


Hide All
1Burt, B. (2005) Position paper: epidemiology of periodontal diseases. Journal of Periodontology 76, 1406-1419
2Papapanou, P.N. (1999) Epidemiology of periodontal diseases: an update. Journal of the International Academy of Periodontology 1, 110-116
3Eke, P.I. et al. (2012) Prevalence of periodontitis in adults in the United States: 2009 and 2010. Journal of Dental Research 91, 914-920
4Papapanou, P.N. (2012) The prevalence of periodontitis in the US: forget what you were told. Journal of Dental Research 91, 907-908
5Savage, A. et al. (2009) A systematic review of definitions of periodontitis and methods that have been used to identify this disease. Journal of Clinical Periodontology 36, 458-467
6Tezal, M. and Uribe, S. (2011) A lack of consensus in the measurement methods for and definition of periodontitis. J Am Dent Assoc 142, 666-667
7Page, R.C. and Kornman, K.S. (1997) The pathogenesis of human periodontitis: an introduction. Periodontology 2000 14, 9-11
8Darveau, R.P. (2010) Periodontitis: a polymicrobial disruption of host homeostasis. Nature Reviews Microbiology 8, 481-490
9Birkedal-Hansen, H. (1993) Role of cytokines and inflammatory mediators in tissue destruction. Journal of Periodontal Research 28, 500-510
10Hernandez, M. et al. (2011) Host-pathogen interactions in progressive chronic periodontitis. Journal of Dental Research 90, 1164-1170
11Phipps, R.P., Borrello, M.A. and Blieden, T.M. (1997) Fibroblast heterogeneity in the periodontium and other tissues. Journal of Periodontal Research 32, 159-165
12Graves, D. (2008) Cytokines that promote periodontal tissue destruction. Journal of Periodontology 79, 1585-1591
13Bage, T. et al. (2011) Expression of prostaglandin E synthases in periodontitis immunolocalization and cellular regulation. American Journal of Pathology 178, 1676-1688
14Assuma, R. et al. (1998) IL-1 and TNF antagonists inhibit the inflammatory response and bone loss in experimental periodontitis. Journal of Immunology 160, 403-409
15Delima, A.J. et al. (2002) Inflammation and tissue loss caused by periodontal pathogens is reduced by interleukin-1 antagonists. Journal of Infectious Diseases 186, 511-516
16Reddy, M.S. et al. (1993) Efficacy of meclofenamate sodium (Meclomen) in the treatment of rapidly progressive periodontitis. Journal of Clinical Periodontology 20, 635-640
17Silva, T.A. et al. (2007) Chemokines in oral inflammatory diseases: apical periodontitis and periodontal disease. Journal of Dental Research 86, 306-319
18Bartold, P.M., Cantley, M.D. and Haynes, D.R. (2010) Mechanisms and control of pathologic bone loss in periodontitis. Periodontology 2000 53, 55-69
19Tanabe, N. et al. (2005) IL-1 alpha stimulates the formation of osteoclast-like cells by increasing M-CSF and PGE2 production and decreasing OPG production by osteoblasts. Life Sciences 77, 615-626
20Bascones, A. et al. (2005) Tissue destruction in periodontitis: bacteria or cytokines fault? Quintessence International 36, 299-306
21Page, R.C. et al. (1997) Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontology 2000 14, 216-248
22Pihlstrom, B.L., Michalowicz, B.S. and Johnson, N.W. (2005) Periodontal diseases. Lancet 366, 1809-1820
23Lindhe, J., Hamp, S. and Loe, H. (1973) Experimental periodontitis in the beagle dog. Journal of Periodontal Research 8, 1-10
24Loe, H., Theilade, E. and Jensen, S.B. (1965) Experimental gingivitis in man. Journal of Periodontology 36, 177-187
25Kornman, K.S. (2008) Mapping the pathogenesis of periodontitis: a new look. Journal of Periodontology 79, 1560-1568
26Page, R.C. and Schroeder, H.E. (1976) Pathogenesis of inflammatory periodontal disease: a summary of current work. Laboratory Investigation 34, 235-249
27Ranney, R.R. (1991) Immunologic mechanisms of pathogenesis in periodontal diseases: an assessment. Journal of Periodontal Research 26, 243-254
28Seymour, G.J. (1987) Possible mechanisms involved in the immunoregulation of chronic inflammatory periodontal disease. Journal of Dental Research 66, 2-9
29Corey, L.A. et al. (1993) Self-reported periodontal disease in a Virginia twin population. Journal of Periodontology 64, 1205-1208
30Michalowicz, B.S. et al. (2000) Evidence of a substantial genetic basis for risk of adult periodontitis. Journal of Periodontology 71, 1699-1707
31Kornman, K.S., Page, R.C. and Tonetti, M.S. (1997) The host response to the microbial challenge in periodontitis: assembling the players. Periodontology 2000 14, 33-53
32Madianos, P.N., Bobetsis, Y.A. and Kinane, D.F. (2005) Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. Journal of Clinical Periodontology 32(Suppl 6), 57-71
33Bartold, P.M. and Narayanan, A.S. (2006) Molecular and cell biology of healthy and diseased periodontal tissues. Periodontology 2000 40, 29-49
34Ohlrich, E.J., Cullinan, M.P. and Seymour, G.J. (2009) The immunopathogenesis of periodontal disease. Australian Dental Journal 54(Suppl 1), S2-S10
35Kramer, J.M. and Gaffen, S.L. (2007) Interleukin-17: a new paradigm in inflammation, autoimmunity, and therapy. Journal of Periodontology 78, 1083-1093
36Garlet, G.P. (2010) Destructive and protective roles of cytokines in periodontitis: a re-appraisal from host defense and tissue destruction viewpoints. Journal of Dental Research 89, 1349-1363
37Van Dyke, T.E. and van Winkelhoff, A.J. (2013) Infection and inflammatory mechanisms. Journal of Clinical Periodontology 40(Suppl 14), S1-S7
38Darveau, R.P. (2010) Periodontitis: a polymicrobial disruption of host homeostasis. Nature Reviews Microbiology 8, 481-490
39Holt, S.C. and Ebersole, J.L. (2005) Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia: the “red complex”, a prototype polybacterial pathogenic consortium in periodontitis. Periodontology 2000 38, 72-122
40Mahanonda, R. and Pichyangkul, S. (2007) Toll-like receptors and their role in periodontal health and disease. Periodontology 2000 43, 41-55
41Van Dyke, T.E. and Serhan, C.N. (2003) Resolution of inflammation: a new paradigm for the pathogenesis of periodontal diseases. Journal of Dental Research 82, 82-90
42Serhan, C.N., Chiang, N. and Van Dyke, T.E. (2008) Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nature Reviews Immunology 8, 349-361
43Nistala, K. and Wedderburn, L.R. (2009) Th17 and regulatory T cells: rebalancing pro- and anti-inflammatory forces in autoimmune arthritis. Rheumatology (Oxford) 48, 602-606
44Andre, S. et al. (2009) Surveillance of antigen-presenting cells by CD4+ CD25+ regulatory T cells in autoimmunity: immunopathogenesis and therapeutic implications. American Journal of Pathology 174, 1575-1587
45Okui, T. et al. (2012) The presence of IL-17 + /FOXP3+ double-positive cells in periodontitis. Journal of Dental Research 91, 574-579
46Flavell, S.J. et al. (2008) Fibroblasts as novel therapeutic targets in chronic inflammation. British Journal of Pharmacology 153, S241-S246
47Heath, J.K. et al. (1987) Bacterial antigens induce collagenase and prostaglandin E2 synthesis in human gingival fibroblasts through a primary effect on circulating mononuclear cells. Infection and Immunity 55, 2148-2154
48Meikle, M.C. et al. (1994) Immunolocalization of matrix metalloproteinases and TIMP-1 (tissue inhibitor of metalloproteinases) in human gingival tissues from periodontitis patients. Journal of Periodontal Research 29, 118-126
49Reynolds, J.J. and Meikle, M.C. (1997) Mechanisms of connective tissue matrix destruction in periodontitis. Periodontology 2000 14, 144-157
50Bage, T. et al. (2010) Signal pathways JNK and NF-kappaB, identified by global gene expression profiling, are involved in regulation of TNFalpha-induced mPGES-1 and COX-2 expression in gingival fibroblasts. BMC Genomics 11, 241–200
51Domeij, H., Modeer, T. and Yucel-Lindberg, T. (2004) Matrix metalloproteinase-1 and tissue inhibitor of metalloproteinase-1 production in human gingival fibroblasts: the role of protein kinase C. Journal of Periodontal Research 39, 308-314
52Nishikawa, M. et al. (2002) Effects of TNFalpha and prostaglandin E2 on the expression of MMPs in human periodontal ligament fibroblasts. Journal of Periodontal Research 37, 167-176
53Noguchi, K., Shitashige, M. and Ishikawa, I. (1999) Involvement of cyclooxygenase-2 in interleukin-1alpha-induced prostaglandin production by human periodontal ligament cells. Journal of Periodontology 70, 902-908
54Hormdee, D. et al. (2005) Protein kinase-A-dependent osteoprotegerin production on interleukin-1 stimulation in human gingival fibroblasts is distinct from periodontal ligament fibroblasts. Clinical and Experimental Immunology 142, 490-497
55Holmlund, A., Hanstrom, L. and Lerner, U.H. (2004) Bone resorbing activity and cytokine levels in gingival crevicular fluid before and after treatment of periodontal disease. Journal of Clinical Periodontology 31, 475-482
56Thunell, D.H. et al. (2010) A multiplex immunoassay demonstrates reductions in gingival crevicular fluid cytokines following initial periodontal therapy. Journal of Periodontal Research 45, 148-152
57Tymkiw, K.D. et al. (2011) Influence of smoking on gingival crevicular fluid cytokines in severe chronic periodontitis. Journal of Clinical Periodontology 38, 219-228
58Ishihara, Y. et al. (1997) Gingival crevicular interleukin-1 and interleukin-1 receptor antagonist levels in periodontally healthy and diseased sites. Journal of Periodontal Research 32, 524-529
59Gamonal, J. et al. (2000) Levels of interleukin-1 beta, -8, and -10 and RANTES in gingival crevicular fluid and cell populations in adult periodontitis patients and the effect of periodontal treatment. Journal of Periodontology 71, 1535-1545
60Rescala, B. et al. (2010) Immunologic and microbiologic profiles of chronic and aggressive periodontitis subjects. Journal of Periodontology 81, 1308-1316
61Giannopoulou, C., Kamma, J.J. and Mombelli, A. (2003) Effect of inflammation, smoking and stress on gingival crevicular fluid cytokine level. Journal of Clinical Periodontology 30, 145-153
62Ertugrul, A.S. et al. (2013) Comparison of CCL28, interleukin-8, interleukin-1beta and tumor necrosis factor-alpha in subjects with gingivitis, chronic periodontitis and generalized aggressive periodontitis. Journal of Periodontal Research 48, 44-51
63Fujita, Y. et al. (2012) Correlations between pentraxin 3 or cytokine levels in gingival crevicular fluid and clinical parameters of chronic periodontitis. Odontology 100, 215-221
64Cetinkaya, B. et al. (2013) Proinflammatory and anti-inflammatory cytokines in gingival crevicular fluid and serum of patients with rheumatoid arthritis and patients with chronic periodontitis. Journal of Periodontology 84, 84-93
65Lo, Y.J. et al. (1999) Interleukin 1beta-secreting cells in inflamed gingival tissue of adult periodontitis patients. Cytokine 11, 626-633
66Hou, L.T. et al. (2003) Interleukin-1beta, clinical parameters and matched cellular-histopathologic changes of biopsied gingival tissue from periodontitis patients. Journal of Periodontal Research 38, 247-254
67Calderin, S., Garcia-Nunez, J.A. and Gomez, C. (2013) Short-term clinical and osteoimmunological effects of scaling and root planing complemented by simple or repeated laser phototherapy in chronic periodontitis. Lasers in Medical Science 28, 157-166
68Pradeep, A.R., Roopa, Y. and Swati, P.P. (2008) Interleukin-4, a T-helper 2 cell cytokine, is associated with the remission of periodontal disease. Journal of Periodontal Research 43, 712-716
69Tsai, C.C. et al. (2007) Changes in gingival crevicular fluid interleukin-4 and interferon-gamma in patients with chronic periodontitis before and after periodontal initial therapy. Kaohsiung Journal of Medical Sciences 23, 1-7
70Zhao, L. et al. (2011) Effect of non-surgical periodontal therapy on the levels of Th17/Th1/Th2 cytokines and their transcription factors in Chinese chronic periodontitis patients. Journal of Clinical Periodontology 38, 509-516
71Kurtis, B. et al. (1999) IL-6 levels in gingival crevicular fluid (GCF) from patients with non-insulin dependent diabetes mellitus (NIDDM), adult periodontitis and healthy subjects. Journal of Oral Sciences 41, 163-167
72Gamonal, J. et al. (2001) Characterization of cellular infiltrate, detection of chemokine receptor CCR5 and interleukin-8 and RANTES chemokines in adult periodontitis. Journal of Periodontal Research 36, 194-203
73Sanchez-Hernandez, P.E., et al. (2011) IL-12 and IL-18 levels in serum and gingival tissue in aggressive and chronic periodontitis. Oral Diseases 17, 522-529
74Honda, T. et al. (2008) Elevated expression of IL-17 and IL-12 genes in chronic inflammatory periodontal disease. Clinica Chimica Acta 395, 137-141
75Vernal, R. et al. (2005) Levels of interleukin-17 in gingival crevicular fluid and in supernatants of cellular cultures of gingival tissue from patients with chronic periodontitis. Journal of Clinical Periodontology 32, 383-389
76Pradeep, A.R. et al. (2009) Correlation of gingival crevicular fluid interleukin-18 and monocyte chemoattractant protein-1 levels in periodontal health and disease. Journal of Periodontology 80, 1454-1461
77Dutzan, N. et al. (2011) Levels of interleukin-21 in patients with untreated chronic periodontitis. Journal of Periodontology 82, 1483-1489
78Dutzan, N. et al. (2009) Levels of interferon-gamma and transcription factor T-bet in progressive periodontal lesions in patients with chronic periodontitis. Journal of Periodontology 80, 290-296
79Kurtis, B. et al. (2005) Gingival crevicular fluid levels of monocyte chemoattractant protein-1 and tumor necrosis factor-alpha in patients with chronic and aggressive periodontitis. Journal of Periodontology 76, 1849-1855
80Tervahartiala, T. et al. (2001) Tumor necrosis factor-alpha and its receptors, p55 and p75, in gingiva of adult periodontitis. Journal of Dental Research 80, 1535-1539
81de Lima Oliveira, A.P. et al. (2012) Effects of periodontal therapy on GCF cytokines in generalized aggressive periodontitis subjects. Journal of Clinical Periodontology 39, 295-302
82de Oliveira, R.R. et al. (2009) Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: cytokine profile in gingival crevicular fluid, preliminary results. Journal of Periodontology 80, 98-105
83Garlet, G.P. et al. (2003) Patterns of chemokines and chemokine receptors expression in different forms of human periodontal disease. Journal of Periodontal Research 38, 210-217
84Deo, V. and Bhongade, M.L. (2010) Pathogenesis of periodontitis: role of cytokines in host response. Dentistry Today 29, 60-62, 64–6; quiz 68–9
85Prabhu, A., Michalowicz, B.S. and Mathur, A. (1996) Detection of local and systemic cytokines in adult periodontitis. Journal of Periodontology 67, 515-522
86Marcaccini, A.M. et al. (2009) Circulating interleukin-6 and high-sensitivity C-reactive protein decrease after periodontal therapy in otherwise healthy subjects. Journal of Periodontology 80, 594-602
87Graves, D.T. and Cochran, D. (2003) The contribution of interleukin-1 and tumor necrosis factor to periodontal tissue destruction. Journal of Periodontology 74, 391-401
88Perozini, C. et al. (2010) Gingival crevicular fluid biochemical markers in periodontal disease: a cross-sectional study. Quintessence International 41, 877-883
89Stashenko, P. et al. (1991) Tissue levels of bone resorptive cytokines in periodontal disease. Journal of Periodontology 62, 504-509
90Gaspersic, R. et al. (2003) Influence of subcutaneous administration of recombinant TNF-alpha on ligature-induced periodontitis in rats. Journal of Periodontal Research 38, 198-203
91Pers, J.O. et al. (2008) Anti-TNF-alpha immunotherapy is associated with increased gingival inflammation without clinical attachment loss in subjects with rheumatoid arthritis. Journal of Periodontology 79, 1645-1651
92Koide, M. et al. (1995) In vivo administration of IL-1 beta accelerates silk ligature-induced alveolar bone resorption in rats. Journal of Oral Pathology and Medicine 24, 420-434
93Delima, A.J. et al. (2001) Soluble antagonists to interleukin-1 (IL-1) and tumor necrosis factor (TNF) inhibits loss of tissue attachment in experimental periodontitis. Journal of Clinical Periodontology 28, 233-240
94Weber, A., Wasiliew, P. and Kracht, M. (2010) Interleukin-1 (IL-1) pathway. Sci Signalling 3, cm1
95Kwan Tat, S. et al. (2004) IL-6, RANKL, TNF-alpha/IL-1: interrelations in bone resorption pathophysiology. Cytokine and Growth Factor Reviews 15, 49-60
96Yucel-Lindberg, T., Nilsson, S. and Modeer, T. (1999) Signal transduction pathways involved in the synergistic stimulation of prostaglandin production by interleukin-1beta and tumor necrosis factor alpha in human gingival fibroblasts. Journal of Dental Research 78, 61-68
97Huang, G.T., Haake, S.K. and Park, N.H. (1998) Gingival epithelial cells increase interleukin-8 secretion in response to Actinobacillus actinomycetemcomitans challenge. Journal of Periodontology 69, 1105-1110
98Liu, R.K. et al. (2001) Polymorphonuclear neutrophils and their mediators in gingival tissues from generalized aggressive periodontitis. Journal of Periodontology 72, 1545-1553
99Preshaw, P.M. and Taylor, J.J.How has research into cytokine interactions and their role in driving immune responses impacted our understanding of periodontitis? Journal of Clinical Periodontology 38(Suppl 11), 60-84
100Nikolopoulos, G.K. et al. (2008) Cytokine gene polymorphisms in periodontal disease: a meta-analysis of 53 studies including 4178 cases and 4590 controls. Journal of Clinical Periodontology 35, 754-767
101Zhang, J. et al. (2011) Gene polymorphisms and periodontitis. Periodontology 2000 56, 102-124
102McDevitt, M.J. et al. (2000) Interleukin-1 genetic association with periodontitis in clinical practice. Journal of Periodontology 71, 156-163
103Galbraith, G.M. et al. (1999) Polymorphic cytokine genotypes as markers of disease severity in adult periodontitis. Journal of Clinical Periodontology 26, 705-709
104Brett, P.M. et al. (2005) Functional gene polymorphisms in aggressive and chronic periodontitis. Journal of Dental Research 84, 1149-1153
105Zhong, Q. et al. (2012) Interleukin-10 gene polymorphisms and chronic/aggressive periodontitis susceptibility: a meta-analysis based on 14 case-control studies. Cytokine 60, 47-54
106Fassmann, A. et al. (2003) Polymorphisms in the +252(A/G) lymphotoxin-alpha and the -308(A/G) tumor necrosis factor-alpha genes and susceptibility to chronic periodontitis in a Czech population. Journal of Periodontal Research 38, 394-399
107Peters-Golden, M. and Henderson, W.R. Jr (2007) Leukotrienes. New England Journal of Medicine 357, 1841-1854
108Hikiji, H. et al. (2008) The roles of prostanoids, leukotrienes, and platelet-activating factor in bone metabolism and disease. Progress in Lipid Research 47, 107-126
109Pradeep, A.R. et al. (2007) Gingival crevicular fluid levels of leukotriene B4 in periodontal health and disease. Journal of Periodontology 78, 2325-2330
110Back, M. et al. (2007) Increased leukotriene concentrations in gingival crevicular fluid from subjects with periodontal disease and atherosclerosis. Atherosclerosis 193, 389-394
111Hasturk, H. et al. (2006) RvE1 protects from local inflammation and osteoclast- mediated bone destruction in periodontitis. FASEB Journal 20, 401-403
112Herrera, B.S. et al. (2008) An endogenous regulator of inflammation, resolvin E1, modulates osteoclast differentiation and bone resorption. British Journal of Pharmacology 155, 1214-1223
113Fredman, G., et al. Impaired phagocytosis in localized aggressive periodontitis: rescue by Resolvin E1. PLoS ONE 6, e24422
114Wan, M. et al. (2011) Leukotriene B4/antimicrobial peptide LL-37 proinflammatory circuits are mediated by BLT1 and FPR2/ALX and are counterregulated by lipoxin A4 and resolvin E1. FASEB Journal 25, 1697-1705
115Funk, C.D. (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294, 1871-1875
116Harris, S.G. et al. (2002) Prostaglandins as modulators of immunity. Trends in Immunology 23, 144-150
117Bergstrom, S. (1967) Prostaglandins: members of a new hormonal system. These physiologically very potent compounds of ubiquitous occurrence are formed from essential fatty acids. Science 157, 382-391
118Samuelsson, B. et al. (1975) Prostaglandins. Annual Review of Biochemistry 44, 669-695
119Granstrom, E. (1984) The arachidonic acid cascade. The prostaglandins, thromboxanes and leukotrienes. Inflammation 8(Suppl), S15-S25
120Noguchi, K. and Ishikawa, I. (2007) The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease. Periodontology 2000 43, 85-101
121Kaneko, H. et al. (2007) Effects of prostaglandin E2 and lipopolysaccharide on osteoclastogenesis in RAW 264.7 cells. Prostaglandins Leukot Essent Fatty Acids 77, 181-186
122Raisz, L.G. (1990) The role of prostaglandins in the local regulation of bone metabolism. Progress in Clinical and Biological Research 332, 195-203
123Blackwell, K.A., Raisz, L.G. and Pilbeam, C.C. (2010) Prostaglandins in bone: bad cop, good cop? Trends in Endocrinology and Metabolism 21, 294-301
124Suzawa, T. et al. (2000) The role of prostaglandin E receptor subtypes (EP1, EP2, EP3, and EP4) in bone resorption: an analysis using specific agonists for the respective EPs. Endocrinology 141, 1554-1559
125Miyaura, C. et al. (2000) Impaired bone resorption to prostaglandin E2 in prostaglandin E receptor EP4-knockout mice. Journal of Biological Chemistry 275, 19819-19823
126ElAttar, T.M. (1976) Prostaglandin E2 in human gingiva in health and disease and its stimulation by female sex steroids. Prostaglandins 11, 331-341
127Eberhard, J. et al. (2000) Quantitation of arachidonic acid metabolites in small tissue biopsies by reversed-phase high-performance liquid chromatography. Analytical Biochemistry 280, 258-263
128Vardar, S., Baylas, H. and Huseyinov, A. (2003) Effects of selective cyclooxygenase-2 inhibition on gingival tissue levels of prostaglandin E2 and prostaglandin F2alpha and clinical parameters of chronic periodontitis. Journal of Periodontology 74, 57-63
129Offenbacher, S., Heasman, P.A. and Collins, J.G. (1993) Modulation of host PGE2 secretion as a determinant of periodontal disease expression. Journal of Periodontology 64, 432-444
130Preshaw, P.M. and Heasman, P.A. (2002) Prostaglandin E2 concentrations in gingival crevicular fluid: observations in untreated chronic periodontitis. Journal of Clinical Periodontology 29, 15-20
131Offenbacher, S., Odle, B.M. and Van Dyke, T.E. (1986) The use of crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss. Journal of Periodontal Research 21, 101-112
132Champagne, C.M. et al. (2003) Potential for gingival crevice fluid measures as predictors of risk for periodontal diseases. Periodontology 2000 31, 167-180
133Schaefer, A.S. et al. (2010) COX-2 is associated with periodontitis in Europeans. Journal of Dental Research 89, 384-388
134Zhang, S. et al. (2010) Alteration of PTGS2 promoter methylation in chronic periodontitis. Journal of Dental Research 89, 133-137
135Nichols, F. and Maraj, B. (1998) Relationship between hydroxy fatty acids and prostaglandin E2 in gingival tissue. Infection and Immunity 66, 5805-5811
136Potempa, J., Banbula, A. and Travis, J. (2000) Role of bacterial proteinases in matrix destruction and modulation of host responses. Periodontology 2000 24, 153-192
137Laugisch, O. et al. (2012) Periodontal pathogens affect the level of protease inhibitors in gingival crevicular fluid. Molecular Oral Microbiology 27, 45-56
138Sorsa, T. et al. (2006) Matrix metalloproteinases: contribution to pathogenesis, diagnosis and treatment of periodontal inflammation. Annals of Medicine 38, 306-321
139McMillan, S.J. et al. (2004) Matrix metalloproteinase-9 deficiency results in enhanced allergen-induced airway inflammation. Journal of Immunology 172, 2586-2594
140Owen, C.A. et al. (2004) Membrane-bound matrix metalloproteinase-8 on activated polymorphonuclear cells is a potent, tissue inhibitor of metalloproteinase-resistant collagenase and serpinase. Journal of Immunology 172, 7791-7803
141Uitto, V.J., Overall, C.M. and McCulloch, C. (2003) Proteolytic host cell enzymes in gingival crevice fluid. Periodontology 2000 31, 77-104
142Sorsa, T., Tjaderhane, L. and Salo, T. (2004) Matrix metalloproteinases (MMPs) in oral diseases. Oral Diseases 10, 311-318
143Gursoy, U.K. et al. (2010) Salivary MMP-8, TIMP-1, and ICTP as markers of advanced periodontitis. Journal of Clinical Periodontology 37, 487-493
144Letra, A. et al. (2012) MMP3 and TIMP1 variants contribute to chronic periodontitis and may be implicated in disease progression. Journal of Clinical Periodontology 39, 707-716
145Li, G. et al. (2012) Association of matrix metalloproteinase (MMP)-1, 3, 9, interleukin (IL)-2, 8 and cyclooxygenase (COX)-2 gene polymorphisms with chronic periodontitis in a Chinese population. Cytokine 60, 552-560
146Domeij, H., Yucel-Lindberg, T. and Modeer, T. (2002) Signal pathways involved in the production of MMP-1 and MMP-3 in human gingival fibroblasts. European Journal of Oral Sciences 110, 302-306
147Domeij, H. et al. (2005) Cell expression of MMP-1 and TIMP-1 in co-cultures of human gingival fibroblasts and monocytes: the involvement of ICAM-1. Biochemical and Biophysical Research Communications 338, 1825-1833
148Abe, M. et al. (2001) Induction of collagenase-2 (matrix metalloproteinase-8) gene expression by interleukin-1beta in human gingival fibroblasts. Journal of Periodontal Research 36, 153-159
149Kuo, P.J. et al. (2012) Cyclosporine-A inhibits MMP-2 and -9 activities in the presence of Porphyromonas gingivalis lipopolysaccharide: an experiment in human gingival fibroblast and U937 macrophage co-culture. Journal of Periodontal Research 47, 431-438
150Zhang, W., Song, F. and Windsor, L.J. (2010) Effects of tobacco and P. gingivalis on gingival fibroblasts. Journal of Dental Research 89, 527-531
151Choi, Y.A. et al. (2004) Interleukin-1beta stimulates matrix metalloproteinase-2 expression via a prostaglandin E2-dependent mechanism in human chondrocytes. Experimental and Molecular Medicine 36, 226-232
152Khan, K.M. et al. (2012) Matrix metalloproteinase-dependent microsomal prostaglandin E synthase-1 expression in macrophages: role of TNF-alpha and the EP4 prostanoid receptor. Journal of Immunology 188, 1970-1980
153Gosset, M. et al. (2010) Inhibition of matrix metalloproteinase-3 and -13 synthesis induced by IL-1beta in chondrocytes from mice lacking microsomal prostaglandin E synthase-1. Journal of Immunology 185, 6244-6252
154Kida, Y. et al. (2005) Interleukin-1 stimulates cytokines, prostaglandin E2 and matrix metalloproteinase-1 production via activation of MAPK/AP-1 and NF-kappaB in human gingival fibroblasts. Cytokine 29, 159-168
155Kim, C.H. et al. (2005) PGE2 induces the gene expression of bone matrix metalloproteinase-1 in mouse osteoblasts by cAMP-PKA signaling pathway. International Journal of Biochemistry and Cell Biology 37, 375-385
156Verstappen, J. and Von den Hoff, J.W. (2006) Tissue inhibitors of metalloproteinases (TIMPs): their biological functions and involvement in oral disease. Journal of Dental Research 85, 1074-1084
157Soell, M., Elkaim, R. and Tenenbaum, H. (2002) Cathepsin C, matrix metalloproteinases, and their tissue inhibitors in gingiva and gingival crevicular fluid from periodontitis-affected patients. Journal of Dental Research 81, 174-178
158Golub, L.M. et al. (1998) Tetracyclines inhibit connective tissue breakdown by multiple non-antimicrobial mechanisms. Advances in Dental Research 12, 12-26
159Braun, T. and Zwerina, J. (2011) Positive regulators of osteoclastogenesis and bone resorption in rheumatoid arthritis. Arthritis Research and Therapy 13, 235
160Schett, G. (2011) Effects of inflammatory and anti-inflammatory cytokines on the bone. European Journal of Clinical Investigation 41, 1361-1366
161Takayanagi, H. (2005) Mechanistic insight into osteoclast differentiation in osteoimmunology. Journal of Molecular Medicine (Berlin) 83, 170-179
162Maeda, K. et al. (2012) Wnt5a-Ror2 signaling between osteoblast-lineage cells and osteoclast precursors enhances osteoclastogenesis. Nature Medicine 18, 405-412
163Kinane, D.F. et al. (2011) Host-response: understanding the cellular and molecular mechanisms of host-microbial interactions–consensus of the Seventh European Workshop on Periodontology. Journal of Clinical Periodontology 38 (Suppl 11), 44-48
164Mogi, M. et al. (2004) Differential expression of RANKL and osteoprotegerin in gingival crevicular fluid of patients with periodontitis. Journal of Dental Research 83, 166-169
165Pfeilschifter, J. et al. (1989) Interleukin-1 and tumor necrosis factor stimulate the formation of human osteoclastlike cells in vitro. Journal of Bone Mineral Research 4, 113-118
166Wei, S. et al. (2005) IL-1 mediates TNF-induced osteoclastogenesis. Journal of Clinical Investigation 115, 282-290
167Brechter, A.B. and Lerner, U.H. (2007) Bradykinin potentiates cytokine-induced prostaglandin biosynthesis in osteoblasts by enhanced expression of cyclooxygenase 2, resulting in increased RANKL expression. Arthritis and Rheumatism 56, 910-923
168Axmann, R. et al. (2009) Inhibition of interleukin-6 receptor directly blocks osteoclast formation in vitro and in vivo. Arthritis and Rheumatism 60, 2747-2756
169Jimi, E. et al. (2004) Selective inhibition of NF-kappa B blocks osteoclastogenesis and prevents inflammatory bone destruction in vivo. Nature Medicine 10, 617-624
170Choi, B.K. et al. (2005) Prostaglandin E(2) is a main mediator in receptor activator of nuclear factor-kappaB ligand-dependent osteoclastogenesis induced by Porphyromonas gingivalis, Treponema denticola, and Treponema socranskii. Journal of Periodontology 76, 813-820
171Brandstrom, H. et al. (1998) Regulation of osteoprotegerin mRNA levels by prostaglandin E2 in human bone marrow stroma cells. Biochemical and Biophysical Research Communications 247, 338-341
172Souza, J.A. et al. (2012) Modulation of host cell signaling pathways as a therapeutic approach in periodontal disease. Journal of Applied Oral Science 20, 128-138
173Giannobile, W.V. (2008) Host-response therapeutics for periodontal diseases. Journal of Periodontology 79, 1592-1600
174Bingham, C.O. III and Austen, K.F. (1999) Phospholipase A2 enzymes in eicosanoid generation. Proceedings of the Association of American Physicians 111, 516-524
175Needleman, P. (1978) Characterization of the reaction sequence involved in phospholipid labeling and deacylation and prostaglandin synthesis and actions. Journal of Allergy and Clinical Immunology 62, 96-102
176Smith, W.L. and Song, I. (2002) The enzymology of prostaglandin endoperoxide H synthases-1 and -2. Prostaglandins and Other Lipid Mediators 68–69, 115-128
177Smith, W.L., Marnett, L.J. and DeWitt, D.L. (1991) Prostaglandin and thromboxane biosynthesis. Pharmacology and Therapeutics 49, 153-179
178Jakobsson, P.J. et al. (1999) Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proceedings of the National Academy of Sciences of the United States of America 96, 7220-7225
179Watanabe, K. et al. (1997) Two types of microsomal prostaglandin E synthase: glutathione-dependent and -independent prostaglandin E synthases. Biochemical and Biophysical Research Communications 235, 148-152
180Vane, J.R. (1971) Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nature New Biology 231, 232-235
181Rouzer, C.A. and Marnett, L.J. (2009) Cyclooxygenases: structural and functional insights. Journal of Lipid Research 50(Suppl), S29-S34
182Fracon, R.N. et al. (2008) Prostaglandins and bone: potential risks and benefits related to the use of nonsteroidal anti-inflammatory drugs in clinical dentistry. Journal of Oral Science 50, 247-252
183Salvi, G.E. and Lang, N.P. (2005) The effects of non-steroidal anti-inflammatory drugs (selective and non-selective) on the treatment of periodontal diseases. Current Pharmaceutical Design 11, 1757-1769
184Faizuddin, M. et al. (2012) Association between long-term aspirin use and periodontal attachment level in humans: a cross-sectional investigation. Australian Dental Journal 57, 45-50
185Buduneli, N. et al. (2010) Clinical findings and gingival crevicular fluid prostaglandin E2 and interleukin-1-beta levels following initial periodontal treatment and short-term meloxicam administration. Expert Opin on Pharmacotherapy 11, 1805-1812
186Vardar-Sengul, S. et al. (2008) The effects of selective COX-2 inhibitor/celecoxib and omega-3 fatty acid on matrix metalloproteinases, TIMP-1, and laminin-5gamma2-chain immunolocalization in experimental periodontitis. Journal of Periodontology 79, 1934-1941
187Funk, C.D. and FitzGerald, G.A. (2007) COX-2 inhibitors and cardiovascular risk. Journal of Cardiovascular Pharmacology 50, 470-479
188Friesen, R.W. and Mancini, J.A. (2008) Microsomal prostaglandin E2 synthase-1 (mPGES-1): a novel anti-inflammatory therapeutic target. Journal of Medicinal Chemistry 51, 4059-4067
189Koeberle, A. and Werz, O. (2009) Inhibitors of the microsomal prostaglandin E(2) synthase-1 as alternative to non steroidal anti-inflammatory drugs (NSAIDs)–a critical review. Current Medicinal Chemistry 16, 4274-4296
190Giroux, A. et al. (2009) Discovery of disubstituted phenanthrene imidazoles as potent, selective and orally active mPGES-1 inhibitors. Bioorganic and Medicinal Chemistry Letters 19, 5837-5841
191Riendeau, D. et al. (2005) Inhibitors of the inducible microsomal prostaglandin E2 synthase (mPGES-1) derived from MK-886. Bioorganic and Medicinal Chemistry Letters 15, 3352-3355
192Koeberle, A., Northoff, H. and Werz, O. (2009) Curcumin blocks prostaglandin E2 biosynthesis through direct inhibition of the microsomal prostaglandin E2 synthase-1. Molecular Cancer Therapeutics 8, 2348-2355
193Koeberle, A. et al. (2009) Green tea epigallocatechin-3-gallate inhibits microsomal prostaglandin E(2) synthase-1. Biochemical and Biophysical Research Communications 388, 350-354
194Xu, D. et al. (2008) MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl)-isophthalonitrile], a selective microsomal prostaglandin E synthase-1 inhibitor, relieves pyresis and pain in preclinical models of inflammation. Journal of Pharmacology and Experimental Therapeutics 326, 754-763
195Guerrero, M.D. et al. (2009) Anti-inflammatory and analgesic activity of a novel inhibitor of microsomal prostaglandin E synthase-1 expression. European Journal of Pharmacology 620, 112-119
196Bruno, A. et al. (2010) Effects of AF3442 [N-(9-ethyl-9H-carbazol-3-yl)-2-(trifluoromethyl)benzamide], a novel inhibitor of human microsomal prostaglandin E synthase-1, on prostanoid biosynthesis in human monocytes in vitro. Biochem Pharmacol 79, 974-981
197Mbalaviele, G. et al. (2010) Distinction of microsomal prostaglandin E synthase-1 (mPGES-1) inhibition from cyclooxygenase-2 inhibition in cells using a novel, selective mPGES-1 inhibitor. Biochemical Pharmacology 79, 1445-1454
198Guimaraes, M.R. et al. (2011) Potent anti-inflammatory effects of systemically administered curcumin modulate periodontal disease in vivo. Journal of Periodontal Research 46, 269-279
199Kats, A. et al. (2013) Inhibition of microsomal prostaglandin E synthase-1 by aminothiazoles decreases prostaglandin E2 synthesis in vitro and ameliorates experimental periodontitis in vivo. FASEB Journal 27, 2328-2341
200Yen, C.A. et al. (2008) The effect of a selective cyclooxygenase-2 inhibitor (celecoxib) on chronic periodontitis. Journal of Periodontology 79, 104-113
201Taylor, P.C. and Feldmann, M. (2009) Anti-TNF biologic agents: still the therapy of choice for rheumatoid arthritis. Nature Reviews Rheumatology 5, 578-582
202Han, J.Y. and Reynolds, M.A. (2012) Effect of anti-rheumatic agents on periodontal parameters and biomarkers of inflammation: a systematic review and meta-analysis. Journal of Periodontal and Implant Science 42, 3-12
203Han, Z. et al. (1999) Jun N-terminal kinase in rheumatoid arthritis. Journal of Pharmacology and Experimental Therapeutics 291, 124-130
204Mitsuyama, K. et al. (2006) Pro-inflammatory signaling by Jun-N-terminal kinase in inflammatory bowel disease. International Journal of Molecular Medicine 17, 449-455
205Li, Q. et al. (2011) Silencing mitogen-activated protein kinase-activated protein kinase-2 arrests inflammatory bone loss. Journal of Pharmacology and Experimental Therapeutics 336, 633-642
206Kirkwood, K.L. et al. (2007) A p38alpha selective mitogen-activated protein kinase inhibitor prevents periodontal bone loss. Journal of Pharmacology and Experimental Therapeutics 320, 56-63
207Li, Q., Valerio, M.S. and Kirkwood, K.L. (2012) MAPK usage in periodontal disease progression. Journal of Signal Transduction 2012, 308943
208Palanisamy, V. et al. (2012) Control of cytokine mRNA expression by RNA-binding proteins and microRNAs. Journal of Dental Research 91, 651-658
209Davanian, H. et al. (2012) Gene expression profiles in paired gingival biopsies from periodontitis-affected and healthy tissues revealed by massively parallel sequencing. PLoS ONE 7, e46440
210Schaefer, A.S. et al. (2010) A genome-wide association study identifies GLT6D1 as a susceptibility locus for periodontitis. Human Molecular Genetics 19, 553-562
211Beikler, T. et al. (2008) Gene expression in periodontal tissues following treatment. BMC Medical Genomics 1, 30
212Demmer, R.T. et al. (2008) Transcriptomes in healthy and diseased gingival tissues. Journal of Periodontology 79, 2112-2124
213Richard, H. et al. (2010) Prediction of alternative isoforms from exon expression levels in RNA-Seq experiments. Nucleic Acids Research 38, e112
214Sultan, M. et al. (2008) A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science 321, 956-960
215Kwok, S.K. et al. (2012) Interleukin-21 promotes osteoclastogenesis in humans with rheumatoid arthritis and in mice with collagen-induced arthritis. Arthritis and Rheumatism 64, 740-751
216Monteleone, G., Pallone, F. and Macdonald, T.T. (2009) Interleukin-21 as a new therapeutic target for immune-mediated diseases. Trends in Pharmacological Sciences 30, 441-447
217Fuss, I.J. et al. (2006) Both IL-12p70 and IL-23 are synthesized during active Crohn's disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody. Inflammatory Bowel Diseases 12, 9-15
218Gottlieb, A. et al. (2009) Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomised, double-blind, placebo-controlled, crossover trial. Lancet 373, 633-640
219Duvallet, E. et al. (2011) Interleukin-23: a key cytokine in inflammatory diseases. Annals of Medicine 43, 503-511
220Tang, C. et al. (2012) Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology 135, 112-124

Related content

Powered by UNSILO

Inflammatory mediators in the pathogenesis of periodontitis

  • Tülay Yucel-Lindberg (a1) and Tove Båge (a1)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed.