Toll Benzeri Reseptörler’in Periodontal Hastalık Patogenezindeki Rolü

Bağışıklık sistemi, doğal ve edinilmiş olmak üzere iki ana bölümden meydana gelir. Doğal bağışıklık sistemi, deri ve mukozal epitelyal bariyerler ile humoral ve hücresel elemanlardan oluşur. İlave olarak, konağın kendine yabancı olan patojenle ilgili molekülleri tanıması ve böylece bağışıklık yanıtın oluşturulmasını sağlayan çeşitli reseptörlere sahiptir. Bu reseptörlerden en iyi bilineni toll benzeri reseptör (TBR) ailesidir. Periodonsiyumun önemli bir savunma bileşeni olan dişeti epitel hücreleri oral mikroorganizmalar ile sürekli temas halindedir. Bu durum, dişeti epitelinde bulunan TBR'lerin sürekli olarak uyarılması ve devamında, ağız sağlığının korunmasına yardımcı olan sitokinlerin ve defensinlerin üretilmesi ile sonuçlanır. Diğer taraftan, konak ve mikroorganizma arasındaki bu dengenin mikroorganizma lehine bozulması sonucu periodontal dokulardaki hastalığın ilerlemesi artar. Bu derlemenin amacı doğal bağışıklık sistemin önemli elemanlarından biri olan TBR’lerin özelliklerini, sinyal iletimini, periodontal hastalıktaki rolünü ve epigenetik düzenlenmesini güncel yayınlar ışığında değerlendirmektir.

Anahtar Kelimeler:

Toll benzeri reseptör, periodontal, hastalık

The Role of Toll-Like Receptors in the Pathogenesisis of Periodontal Disease

Immune system consists of two main parts, named as innate and acquired. The innate immune system consists of skin and mucosal epithelial barriers and humoral and cellular elements. In addition, it has several receptors that allow the host to recognize pathogen related molecules, thereby creating an immune response. The best known of these receptors is the toll-like receptor (TLR) family. Gingival epithelial cells, which are an important defense component of the peridontium, always contact with oral microorganisms. This results in continuous stimulation of TLRs in the gingival epithelium and subsequent production of cytokines and defensins which helps to maintain oral health. On the other hand, as the balance between the host and the microorganism is distrupted in favor of the microorganism, the progression of periodontal breakdown increases. The purpose of this review is to evaluate the characteristics, signal transmission, active role in the pathogenesis of periodontal disease and the epigenetic regulation of TLRs, which are the important elements of the natural immune system, in the light of current publications.

Keywords:

Toll like receptor, periodontal, disease,

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Turvey SE, Broide DH. Innate immunity. Journal of Allergy and Clinical Immunology. 2010; 125(2): 24-32.
Patel P, Chatterjee S. Innate and Adaptive Immunity: Barriers and Receptor-Based Recognition. Immunity and Inflammation in Health and Disease: Elsevier; 2018. p. 3-13.
Medzhitov R, Janeway CA. Innate immunity: the virtues of a nonclonal system of recognition. Cell. 1997; 91(3): 295-8.
Bauernfeind F, Hornung V. Of inflammasomes and pathogens–sensing of microbes by the inflammasome. EMBO molecular medicine. 2013; 5(6): 814-26.
Kutikhin AG, Yuzhalin AE. Pattern recognition receptors and cancer. Frontiers in immunology. 2015; 6: 481.
Kumar H, Kawai T, Akira S. Pathogen recognition by the innate immune system. International reviews of immunology. 2011; 30(1): 16-34.
Botos I, Segal DM, Davies DR. The structural biology of Toll-like receptors. Structure. 2011; 19(4): 447-59.
Akira S, Takeda K. Toll-like receptor signalling. Nature reviews immunology. 2004; 4(7): 499-511.
Lien E, Ingalls RR. Toll-like receptors. Critical care medicine. 2002; 30(1): 1-11.
Ahmed A, Redmond HP, Wang JH. Links between Toll-like receptor 4 and breast cancer. Oncoimmunology. 2013; 2(2): e22945.
Chang Z. Important aspects of Toll-like receptors, ligands and their signaling pathways. Inflammation Research. 2010; 59(10): 791-808.
Kurt-Jones EA, Popova L, Kwinn L, Haynes LM, Jones LP, Tripp RA, et al. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nature immunology. 2000; 1(5): 398-401.
Hasan U, Chaffois C, Gaillard C, Saulnier V, Merck E, Tancredi S, et al. Human TLR10 is a functional receptor, expressed by B cells and plasmacytoid dendritic cells, which activates gene transcription through MyD88. The Journal of Immunology. 2005; 174(5): 2942-50.
Godfroy III JI, Roostan M, Moroz YS, Korendovych IV, Yin H. Isolated Toll-like receptor transmembrane domains are capable of oligomerization. PloS one. 2012; 7(11): e48875.
Yamamoto M, Sato S, Hemmi H, Hoshino K, Kaisho T, Sanjo H, et al. Role of adaptor TRIF in the MyD88-independent toll-like receptor signaling pathway. Science. 2003; 301(5633): 640-3.
Kawai T, Akira S. TLR signaling. Cell Death & Differentiation. 2006; 13(5): 816-25.
Yamamoto M, Sato S, Hemmi H, Uematsu S, Hoshino K, Kaisho T, et al. TRAM is specifically involved in the Toll-like receptor 4–mediated MyD88-independent signaling pathway. Nature immunology. 2003; 4(11): 1144-50.
Kawai T, Akira S, editors. TLR signaling. Seminars in immunology; 2007: Elsevier.
Anwar MA, Basith S, Choi S. Negative regulatory approaches to the attenuation of Toll-like receptor signaling. Experimental & molecular medicine. 2013; 45(2): e11-e.
Kawasaki T, Kawai T. Toll-like receptor signaling pathways. Frontiers in immunology. 2014; 5: 461.
He X, Jing Z, Cheng G. MicroRNAs: new regulators of Toll-like receptor signalling pathways. BioMed research international. 2014; 2014.
Liew FY, Xu D, Brint EK, O'Neill LA. Negative regulation of toll-like receptor-mediated immune responses. Nature Reviews Immunology. 2005; 5(6): 446-58.
Muthukuru M, Jotwani R, Cutler CW. Oral mucosal endotoxin tolerance induction in chronic periodontitis. Infection and immunity. 2005; 73(2): 687-94.
Song B, Zhang Y, Chen L, Zhou T, Huang W, Zhou X, et al. The role of Toll‐like receptors in periodontitis. Oral Diseases. 2017; 23(2): 168-80.
Kusumoto Y, Hirano H, Saitoh K, Yamada S, Takedachi M, Nozaki T, et al. Human gingival epithelial cells produce chemotactic factors interleukin-8 and monocyte chemoattractant protein‐1 after stimulation with Porphyromonas gingivalis via toll‐like receptor 2. Journal of periodontology. 2004; 75(3): 370-9.
Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS. Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontology 2000. 1997; 14(1): 216-48.
Krieg AM. CpG motifs in bacterial DNA and their immune effects. Annual review of immunology. 2002; 20(1): 709-60.
AlQranei MS, Chellaiah MA. Osteoclastogenesis in periodontal diseases: Possible mediators and mechanisms. Journal of Oral Biosciences. 2020.
Lin J, Bi L, Yu X, Kawai T, Taubman MA, Shen B, et al. Porphyromonas gingivalis exacerbates ligature-induced, RANKL-dependent alveolar bone resorption via differential regulation of Toll-like receptor 2 (TLR2) and TLR4. Infection and immunity. 2014; 82(10): 4127-34.
Lin M, Hu Y, Wang Y, Kawai T, Wang Z, Han X. Different engagement of TLR2 and TLR4 in Porphyromonas gingivalis vs. ligature-induced periodontal bone loss. Brazilian oral research. 2017; 31.
Kim PD, Xia-Juan X, Crump KE, Abe T, Hajishengallis G, Sahingur SE. Toll-like receptor 9-mediated inflammation triggers alveolar bone loss in experimental murine periodontitis. Infection and Immunity. 2015; 83(7): 2992-3002.
Crump KE, Oakley JC, Xia-Juan X, Madu TC, Devaki S, Mooney EC, et al. Interplay of toll-like receptor 9, myeloid cells, and deubiquitinase A20 in periodontal inflammation. Infection and immunity. 2017; 85(1).
Madeira M, Queiroz-Junior C, Cisalpino D, Werneck S, Kikuchi H, Fujise O, et al. My D 88 is essential for alveolar bone loss induced by A ggregatibacter actinomycetemcomitans lipopolysaccharide in mice. Molecular oral microbiology. 2013; 28(6): 415-24.
Itoh K, Udagawa N, Kobayashi K, Suda K, Li X, Takami M, et al. Lipopolysaccharide promotes the survival of osteoclasts via Toll-like receptor 4, but cytokine production of osteoclasts in response to lipopolysaccharide is different from that of macrophages. The Journal of Immunology. 2003; 170(7): 3688-95.
Takami M, Kim N, Rho J, Choi Y. Stimulation by toll-like receptors inhibits osteoclast differentiation. The Journal of Immunology. 2002; 169(3): 1516-23.
Gluckman PD, Hanson MA, Buklijas T, Low FM, Beedle AS. Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nature Reviews Endocrinology. 2009; 5(7): 401.
Larsson L, Castilho RM, Giannobile WV. Epigenetics and its role in periodontal diseases: a state‐of‐the‐art review. Journal of periodontology. 2015; 86(4): 556-68.
Benakanakere M, Abdolhosseini M, Hosur K, Finoti L, Kinane D. TLR2 promoter hypermethylation creates innate immune dysbiosis. Journal of dental research. 2015; 94(1): 183-91.
de Faria Amormino SA, Arao TC, Saraiva AM, Gomez RS, Dutra WO, da Costa JE, et al. Hypermethylation and low transcription of TLR2 gene in chronic periodontitis. Human Immunology. 2013; 74(9): 1231-6.
Martins M, Jiao Y, Larsson L, Almeida L, Garaicoa-Pazmino C, Le J, et al. Epigenetic modifications of histones in periodontal disease. Journal of dental research. 2016; 95(2): 215-22.