Inflammatory and Immune Pathways in the Pathogenesis of Periodontal Disease

Overview

Journal Periodontol 2000

Date 2013 Dec 11

PMID 24320956

Citations 490

Authors

Ali Cekici

Alpdogan Kantarci

Hatice Hasturk

Thomas E Van Dyke

Affiliations

Soon will be listed here.

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.

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References

Fonseca J, Santos M, Canhao H, Choy E . Interleukin-6 as a key player in systemic inflammation and joint destruction. Autoimmun Rev. 2009; 8(7):538-42. DOI: 10.1016/j.autrev.2009.01.012. View

Dinarello C . Proinflammatory cytokines. Chest. 2000; 118(2):503-8. DOI: 10.1378/chest.118.2.503. View

Kawai T, Matsuyama T, Hosokawa Y, Makihira S, Seki M, Karimbux N . B and T lymphocytes are the primary sources of RANKL in the bone resorptive lesion of periodontal disease. Am J Pathol. 2006; 169(3):987-98. PMC: 1698808. DOI: 10.2353/ajpath.2006.060180. View

Terricabras E, Benjamim C, Godessart N . Drug discovery and chemokine receptor antagonists: eppur si muove!. Autoimmun Rev. 2004; 3(7-8):550-6. DOI: 10.1016/j.autrev.2004.07.037. View

Kim M, Day C, Selinger C, Magno C, Stephens S, Morrison N . 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. 2005; 281(2):1274-85. DOI: 10.1074/jbc.M510156200. View

Okada N, Kobayashi M, Mugikura K, Okamatsu Y, Hanazawa S, Kitano S . Interleukin-6 production in human fibroblasts derived from periodontal tissues is differentially regulated by cytokines and a glucocorticoid. J Periodontal Res. 1997; 32(7):559-69. DOI: 10.1111/j.1600-0765.1997.tb00932.x. View

Brown J, Zhang J, Keller E . Opg, RANKl, and RANK in cancer metastasis: expression and regulation. Cancer Treat Res. 2004; 118:149-72. DOI: 10.1007/978-1-4419-9129-4_7. View

Bendre M, Montague D, Peery T, Akel N, Gaddy D, Suva L . Interleukin-8 stimulation of osteoclastogenesis and bone resorption is a mechanism for the increased osteolysis of metastatic bone disease. Bone. 2003; 33(1):28-37. DOI: 10.1016/s8756-3282(03)00086-3. View

DAmbrosio D, Iellem A, Bonecchi R, Mazzeo D, Sozzani S, Mantovani A . Selective up-regulation of chemokine receptors CCR4 and CCR8 upon activation of polarized human type 2 Th cells. J Immunol. 1998; 161(10):5111-5. View

10.

Martin T, Sims N . Osteoclast-derived activity in the coupling of bone formation to resorption. Trends Mol Med. 2005; 11(2):76-81. DOI: 10.1016/j.molmed.2004.12.004. View

11.

Serhan C, Brain S, Buckley C, Gilroy D, Haslett C, ONeill L . Resolution of inflammation: state of the art, definitions and terms. FASEB J. 2007; 21(2):325-32. PMC: 3119634. DOI: 10.1096/fj.06-7227rev. View

12.

Linden G, McKinnell J, Shaw C, Lundy F . Substance P and neurokinin A in gingival crevicular fluid in periodontal health and disease. J Clin Periodontol. 1997; 24(11):799-803. DOI: 10.1111/j.1600-051x.1997.tb01192.x. View

13.

Steinhoff M, Vergnolle N, Young S, Tognetto M, Amadesi S, Ennes H . Agonists of proteinase-activated receptor 2 induce inflammation by a neurogenic mechanism. Nat Med. 2000; 6(2):151-8. DOI: 10.1038/72247. View

14.

Bonecchi R, Bianchi G, Bordignon P, DAmbrosio D, Lang R, Borsatti A . Differential expression of chemokine receptors and chemotactic responsiveness of type 1 T helper cells (Th1s) and Th2s. J Exp Med. 1998; 187(1):129-34. PMC: 2199181. DOI: 10.1084/jem.187.1.129. View

15.

Goodson J, Dewhirst F, Brunetti A . Prostaglandin E2 levels and human periodontal disease. Prostaglandins. 1974; 6(1):81-5. DOI: 10.1016/s0090-6980(74)80043-2. View

16.

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(12):2065-77. DOI: 10.1359/JBMR.040910. View

17.

ODorisio M, ODorisio T, Cataland S, Balcerzak S . Vasoactive intestinal polypeptide as a biochemical marker for polymorphonuclear leukocytes. J Lab Clin Med. 1980; 96(4):666-72. View

18.

Bellinger D, Lorton D, Brouxhon S, Felten S, Felten D . The significance of vasoactive intestinal polypeptide (VIP) in immunomodulation. Adv Neuroimmunol. 1996; 6(1):5-27. DOI: 10.1016/s0960-5428(96)00008-3. View

19.

Lundy F, Mullally B, Burden D, Lamey P, Shaw C, Linden G . Changes in substance P and neurokinin A in gingival crevicular fluid in response to periodontal treatment. J Clin Periodontol. 2000; 27(7):526-30. DOI: 10.1034/j.1600-051x.2000.027007526.x. View

20.

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(10):845-55. DOI: 10.1016/0003-9969(90)90010-8. View