* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Host responses in periodontal diseases: a preview
Childhood immunizations in the United States wikipedia , lookup
Vaccination wikipedia , lookup
Sociality and disease transmission wikipedia , lookup
Atherosclerosis wikipedia , lookup
Molecular mimicry wikipedia , lookup
Kawasaki disease wikipedia , lookup
Behçet's disease wikipedia , lookup
Neglected tropical diseases wikipedia , lookup
Sjögren syndrome wikipedia , lookup
Neuromyelitis optica wikipedia , lookup
Inflammatory bowel disease wikipedia , lookup
Multiple sclerosis research wikipedia , lookup
Ankylosing spondylitis wikipedia , lookup
Psychoneuroimmunology wikipedia , lookup
African trypanosomiasis wikipedia , lookup
Autoimmunity wikipedia , lookup
Rheumatoid arthritis wikipedia , lookup
Transmission (medicine) wikipedia , lookup
Globalization and disease wikipedia , lookup
Germ theory of disease wikipedia , lookup
Periodontology 2000, Vol. 43, 2007, 9–13 Printed in Singapore. All rights reserved Ó 2007 The Author. Journal compilation Ó 2007 Blackwell Munksgaard PERIODONTOLOGY 2000 Host responses in periodontal diseases: a preview ISAO ISHIKAWA Ten years have passed since a paradigm shift in the pathogenesis of periodontitis was proposed by Page & Kornman (16). A plethora of research papers has since revised our previous concepts in this field. In particular, important information has appeared on cellular, molecular and genetic aspects of destructive periodontal disease. Recent conceptual and technical advances have provided us with further insights into the infectious agents and the characteristics of the host immune response in periodontal diseases. The information gained may help to improve our ability to diagnose and treat such diseases. In 1997, a symposium at North Carolina Chapel Hill entitled ÔPeriodontal diseases and human health: New edition in periodontal medicineÕ advanced the notion that oral infections may have powerful and multiple influences on the occurrence and severity of systemic conditions and diseases (27). Since then, numerous publications in dental and medical journals have focused on the relationship between periodontal disease and systemic conditions, especially cardiovascular diseases, diabetes and respiratory pathosis. Progress in this field within the last few years has been tremendous. ÔPeriodontal disease and coronary heart disease: a reappraisal of the exposureÕ (1), ÔHigh serum antibody levels to Porphyromonas gingivalis predict myocardial infarctionÕ (19), ÔAntibodies to periodontal pathogens and stroke riskÕ (18), ÔEarly carotid atherosclerosis in subjects with periodontal diseasesÕ (26), ÔGender differences in the relationship between periodontal disease tooth loss, and atherosclerosisÕ (3), ÔPeriodontal disease and biomarkers related to cardiovascular diseasesÕ (7), ÔPeriodontal disease and mortality in type 2 diabetesÕ (22) and ÔOral bacteria in the occluded arteries of patients with Buerger diseaseÕ (6), are titles of recently published articles in medical journals, which have identified a positive correlation between periodontal disease and systemic diseases. Stamm (27) mentioned that practitioners of obstetrics, cardiovascular disease and periodontics are collaborating in scientific progress in ways not previously imagined. Recently, it has been suggested that herpesviruses comprise an important source for triggering periodontal tissue destruction. Herpesvirus infections may initiate or accelerate periodontal breakdown via their ability to stimulate cytokine release from host cells, or they might impair host defense mechanisms, resulting in heightened virulence of resident periodontopathic bacteria (24). In the light of the potential importance of mammalian viruses in periodontal diseases (23–25), a discussion of virally induced host responses is also included in this volume. Microbial antigens and virulence factors elicit an immediate inflammatory and immune response from the host. The host reacts to microbial insults by producing cytokines, eicasonoids, kinins, complement activation products and matrix metalloproteinases. Some of these inflammatory mediators participate in periodontal ligament and bone destruction. In turn, the inflammatory response is regulated by genetic and environmental modifiers. As reported by Page et al. (17), bacteria are essential in, but not sufficient to cause, periodontitis, and host factors, such as heredity, and environmental factors, such as smoking, are important determinants of periodontal disease occurrence and severity. Bacteria may cause periodontal tissue destruction indirectly by activating various components of the host defense system. When activated, these host systems may provide protection at the cost of some level of periodontal destruction. Periodontal researchers have extensively studied this double-edged sword phenomenon, and the concepts thus derived consider the involvement of intrinsic and induced host factors. In addition, cell-specific receptors and their pathways have been identified. In this volume of Periodontology 2000 we have compiled the latest 9 Ishikawa information on host responses in periodontitis. A vast amount of knowledge provided by research experts has been gathered in a format that we hope is clear and illustrative for the readers. In order to investigate the pathogenesis of periodontitis, it is essential to understand how the immune system reacts towards microbial infections. To familiarize readers with this topic, Mahanonda & Pichyangkul (10) have prepared an article on the fundamental mechanisms of host responses to bacterial and viral infections (10). The authors concentrated on two topics: the cross-talk between innate and adaptive immunity mediated by dendritic cells via Toll-like receptors, and the antigen-specific immunoregulation by particular subsets of dendritic cells and T cells. T cells play an important immunoregulatory role in the pathogenesis of periodontal diseases. In a separate article dealing with T cells in periodontal diseases, Gemmell et al. (5) suggest that T cells have a homeostatic role and that autoimmunity is an important component of chronic periodontal inflammation. They discuss various mechanisms by which T cells are involved in the destruction and repair processes of chronic periodontitis. In their article, they advance the concept that T cells have a homeostatic role, rather than a defensive or destructive role, in periodontal diseases (5). Periodontitis is characterized by destruction of the periodontal ligament and bone. Alveolar bone resorption occurs as a result of uncoupling of the normally balanced processes of bone resorption and bone formation. Cytokines, chemokines and prostaglandins have been identified as regulators of the immunoinflammatory process in periodontitis. Activated lymphocytes, macrophages and neutrophils infiltrate inflamed gingival tissue and secrete inflammatory mediators, including interleukin-1 and prostaglandin E2. In addition, T helper 1- and T helper 2-type T lymphocytes, which are present in periodontal lesions, up-regulate the production of the pro-inflammatory interleukin-1 and tumor necrosis factor-a. These cytokines can induce bone resorption indirectly by promoting the differentiation of osteoclast precursors and by activating osteoclasts. Udagawa et al. (28) have prepared a chapter on signal transduction of lipopolysaccharide-induced osteoclast differentiation. Lipopolysaccharide, being the major constituent of gram-negative bacteria, is proposed to be a potent stimulator of bone resorption in inflammatory periodontal disease (28). The recruitment of osteoclasts is dependent on the balance between receptor activator of nuclear factor 10 kappa B ligand and its decoy receptor, osteoprotegerin, in osteoblasts. Receptor activator of nuclear factor kappa B ligand is thought to be a major mediator of alveolar bone resorption in periodontitis. Nagasawa et al. (12) have discussed the role of receptor activator of nuclear factor kappa B, receptor activator of nuclear factor kappa B ligand and osteoprotegerin in periodontal bone resorption. The potential importance of differences in receptor activator of nuclear factor kappa B ligand and osteoprotegerin expression among human gingival fibroblasts, periodontal fibroblasts and osteoblasts is also addressed. In addition, Nagasawa et al. (12) review recent concepts of antibodies against periodontopathic bacteria, especially the diagnostic value of antibacterial antibodies, which are becoming important not only in periodontal diagnosis but also in the risk assessment of coronary heart disease and peripheral vascular disease (4,18). New insights into the classic axis of neutrophils–antibodies–complement in periodontal diseases are also summarized. Prostaglandin E2 is an important mediator of tissue destruction in periodontitis. Prostaglandin E2 stimulates pro-inflammatory responses, including osteoclastogenesis, by enhancing the expression of receptor activator of nuclear factor kappa B ligand. However, prostaglandin E2 also has anti-inflammatory effects, including inhibiting the production of pro-inflammatory cytokines, such as tumor necrosis factor-a, and can elicit anabolic actions on bone. An article by Noguchi & Ishikawa (15), discussing the periodontal roles of prostaglandin E2 and cyclooxygenase-2, has been included. The authors suggest that prostaglandin E2 has the ability to down-regulate hyper-inflammation occurring in periodontal lesions, and to stimulate wound healing. Similarly to environmental factors, host factors, such as heredity, are a major determinant of infectious disease occurrence and severity. With recent advances in the science of genetics, genes responsible for various diseases have been identified and mapped. Genetic traits that may be associated with an increased risk for periodontitis include abnormal phagocyte function, a reduced capacity to produce immunoglobulin G2, hFc-gamma-RIIa polymorphism, tumor necrosis factor-a polymorphism, interleukin-1a polymorphism and prostaglandin endoperoxide synthase 1 gene polymorphism (17). In this volume of Periodontology 2000, Yoshie et al. (29) have reviewed the possible role of genetic polymorphisms in periodontitis. In addition to listing the evidence linking genetics and aggressive and chronic forms of periodontitis, the authors have discussed the Host responses in periodontal diseases: a preview polymorphisms identified in the cytokine family and receptor genes, and addressed the issues and concerns about the candidate gene approach of study in periodontitis. Aggressive periodontitis is characterized by a young age of disease onset and severe periodontal tissue destruction. Meng and co-authors (11) have reviewed the determinants of host susceptibility in aggressive periodontitis, focusing on family aggregation, single nucleotide polymorphisms, polymorphonuclear leukocytes, antibodies, smoking, stress and root morphology abnormalities (11). They suggest that increased host susceptibility in patients with aggressive periodontitis may be caused by the combined effect of multiple genes interacting with environmental factors. Oxidative stress has been implicated in periodontitis, obesity, type II diabetes, vascular diseases and the events that lead to adverse pregnancy outcome. In recent years, reactive oxygen species have also been implicated in the pathogenesis of periodontitis. The overproduction of reactive oxygen species may be a key component of hyper-inflammation associated with periodontitis. Chapple & Matthews (2) explore the role of reactive oxygen and antioxidant species in periodontal tissue destruction. They suggest that oxidative stress not only leads to direct tissue damage, but may also activate key nuclear transcription factors, such as receptor activator of nuclear factor kappa B and Ap-1, which subsequently can induce gene transcription for key pro-inflammatory mediators. Among the environmental factors known to affect the incidence and severity of periodontitis, smoking stands out as one of the most significant and preventable risk factors. Tobacco smoking increases the risk of periodontal destruction by stimulating inflammatory responses and impairing protective/ reparative host responses. In an elaborate review, Ryder (20) deals with the influence of smoking on the immune response in periodontal disease. He suggests that host-modulating agents, such as tetracyclines, may partly alleviate the destructive effects of tobacco products on host responses. Research in the field of tobacco smoking and its effects on the host immune system may also help to identify host-modulating agents that may be beneficial in the treatment of periodontal disease in both smokers and nonsmokers. Diabetes is an extensively researched risk factor for periodontitis. Diabetic subjects are known to respond to microbial challenges in an exaggerated manner compared with nondiabetic subjects. Exaggerated inflammatory responses in diabetic subjects appear to increase the risk for vascular disorders. Nassar et al. (13) have proposed the interesting hypothesis that long-term hyperglycemia supports anaerobic infection in periodontal sites owing to an environment of exacerbated innate immunity. Persistent hyperglycemia may lead to chronically activated innate immunity and chronic inflammation in the periodontium by either blocking or suppressing pathways of resolution. Nassar et al. (13) examined the role of innate immunity, inflammation and resolution of inflammation as essential components in the development of diabetic complications, including periodontal disease. They also proposed several therapeutic approaches, including hostmodulation therapy. In a separate chapter, Nishimura et al. (14) summarize the current knowledge on the bidirectional relationship between diabetes and periodontal disease, and discuss future strategies for the prevention and treatment of periodontal disease in diabetic subjects. Periodontal disease has been considered to be the sixth complication of diabetes. Recent studies suggest that obesity is associated with periodontal disease. Obesity increases the risk of various systemic diseases and of type 2 diabetes, and raises patient mortality. Conversely, periodontal disease has been reported to influence the serum glucose level, not only in diabetic but also in nondiabetic subjects. Taking account of all these issues, the relationship among obesity, diabetes and periodontal disease is complicated and needs to be further evaluated. Saito & Shimazaki (21) have reviewed the relationship between obesity and periodontal disease. The influence of periodontal disease on obesityrelated metabolic disorders, such as glucose and lipid metabolism, and associated glucose intolerance and dyslipidemia, are highlighted (21). With the emergence of immense knowledge at the basic science level, the clinician is left to think about the relevance of the available information. The road from the laboratory bench to the clinic seems sometimes to be exceedingly long. Nonetheless, the information regarding host responses and modulating factors in periodontitis may be used for therapeutic purposes. With the paradigm rapidly changing, the focus in periodontics is shifting from diagnosis and treatment to prevention and health promotion. Identifying and managing the risk factors for periodontitis is of utmost importance. Environmental risk factors, such as tobacco use and diabetes, can be significantly reduced or eliminated by smoking-cessation programs and metabolic control, respectively. Future diagnostic and preventive 11 Ishikawa approaches appear to be in the application of the genetic information to determine the inherent susceptibility of individuals to periodontal disease. Kinane & Bartold (8) have discussed the clinical implications of periodontal host responses. Their chapter may help the clinician bridge the gap between the laboratory and the clinic. To add to this information, Kirkwood et al. (9) have suggested novel therapeutic approaches in periodontics. Alveolar bone loss may be delayed or prevented by the use of host-modulating agents. The feasibility of inhibiting or blocking proteolytic enzymes and pro-inflammatory cytokines are presently being studied. Kirkwood et al. (9) mention three categories of host-modulating agents: antiproteinases, anti-inflammatory drugs, and bone-sparing drugs. More recently, inflammatory cell signaling pathways that generate these inflammatory and tissuedestructive proteinases have also become promising therapeutic targets. Inhibition of signal transduction pathways may abolish cell activation and the production of pro-inflammatory cytokines. Kirkwood et al. (9) propose therapeutic strategies directed towards major signaling pathways, including mitogenactivated protein kinase and receptor activator of nuclear factor kappa B. Finally, they consider novel protein antagonist strategies in the treatment of periodontal diseases to disrupt the receptor activator of nuclear factor kappa B ligand/receptor activator of nuclear factor kappa B/osteoprotegerin axis. These novel therapies may eventually provide more effective means to manage chronic periodontitis. In this volume of Periodontology 2000, we have tried to incorporate the most recent information regarding the host responses in periodontitis. Comprehensive reviews of each study subject have been included. Experts in the field of immunology have contributed their valuable time and effort to complete this task. We hope that this volume is upto-date and of help to the researcher as well as the clinician. As a result of rapidly advancing technology, it may soon be possible to apply the new information for diagnostic and therapeutic purposes. Further research, aimed at a greater understanding of the parasite–host interaction in periodontal infections, may yield significant pay-offs in combating periodontal diseases. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. References 1. Beck JD, Eke P, Heiss G, Madianos P, Couper D, Lin D, Moss K, Elter J, Offenbacher S. Periodontal disease and 12 19. coronary heart disease: a reappraisal of the exposure. Circulation 2005: 112: 19–24. Chapple IL, Matthews JB. The role of reactive oxygen and antioxidant species in periodontal tissue destruction. Periodontol 2000 2006: 43: 160–232. Desvarieux M, Schwahn C, Volzke H, Demmer RT, Ludemann J, Kessler C, Jacobs DR Jr, John U, Kocher T. Gender differences in the relationship between periodontal disease, tooth loss, and atherosclerosis. Stroke 2004: 35: 2029–2035. Engebretson SP, Lamster IB, Elkind MS, Rundek T, Serman NJ, Demmer RT, Sacco RL, Papapanou PN, Desvarieux M. Radiographic measures of chronic periodontitis and carotid artery plaque. Stroke 2005: 36: 561–566. Gemmell E, Yamazaki K, Seymour GJ. The role of T cells in periodontal disease: homeostasis and autoimmunity. Periodontol 2000 2006: 43: 14–40. Iwai T, Inoue Y, Umeda M, Huang Y, Kurihara N, Koike M, Ishikawa I. Oral bacteria in the occluded arteries of patients with Buerger disease. J Vasc Surg 2005: 42: 107–115. Joshipura KJ, Wand HC, Merchant AT, Rimm EB. Periodontal disease and biomarkers related to cardiovascular disease. J Dent Res 2004: 83: 151–155. Kinane DF, Bartold PM. Clinical relevance of the host responses of periodontitis. Periodontol 2000 2006: 43: 278– 293. Kirkwood KL, Cirelli J, Rogers J, Giannobile WV. Novel host response therapeutic approaches to treat periodontal diseases. Periodontol 2000 2006: 43: 294–314. Mahanonda R, Pichyangkul S. Toll-like receptors and their role in periodontal health and disease. Periodontol 2000 2006: 43: 41–55. Meng H, Xu L, Li Q, Han J, Zhao Y. Determinants of host susceptibility in aggressive periodontitis. Periodontol 2000 2006: 43: 133–159. Nagasawa T, Kiji M, Yashiro R, Hormdee D, Lu H, Kunze M, Suda T, Koshy G, Kobayashi H, Oda S, Nitta H, Ishikawa I. Roles of receptor activator of nuclear factor-jB ligand (RANKL) and osteoprotegerin in periodontal health and disease. Periodontol 2000 2006: 43: 65–84. Nassar H, Kantarci A, Van Dyke TE. Diabetic periodontitis: a model for activated innate immunity and impaired resolution of inflammation. Periodontol 2000 2006: 43: 233–244. Nishimura F, Iwamoto Y, Soga Y. The periodontal host response with diabetes. Periodontol 2000 2006: 43: 245– 253. Noguchi K, Ishikawa I. The roles of cyclooxygenase-2 and prostaglandin E2 in periodontal disease. Periodontol 2000 2006: 43: 85–101. Page RC, Kornman KS. The pathogenesis of human periodontitis: an introduction. Periodontol 2000 1997: 14: 9– 11. Page RC, Offenbacher S, Schroeder HE, Seymour GJ, Kornman KS. Advances in the pathogenesis of periodontitis: summary of developments, clinical implications and future directions. Periodontol 2000 1997: 4: 216–248. Pussinen PJ, Alfthan G, Rissanen H, Reunanen A, Asikainen S, Knekt P. Antibodies to periodontal pathogens and stroke risk. Stroke 2004: 35: 2020–2023. Pussinen PJ, Alfthan G, Tuomilehto J, Asikainen S, Jousilahti P. High serum antibody levels to Porphyromonas Host responses in periodontal diseases: a preview 20. 21. 22. 23. 24. gingivalis predict myocardial infarction. Eur J Cardiovasc Prev Rehabil 2004: 11: 408–411. Ryder MI. The influence of smoking on host responses in periodontal infections. Periodontol 2000 2006: 43: 267–277. Saito T, Shimazaki Y. Metabolic disorders related to obesity and periodontal disease. Periodontol 2000 2006: 43: 254– 266. Saremi A, Nelson RG, Tulloch-Reid M, Hanson RL, Sievers ML, Taylor GW, Shlossman M, Bennett PH, Genco R, Knowler WC. Periodontal disease and mortality in type 2 diabetes. Diabetes Care 2005: 28: 27–32. Slots J. Herpesviruses in periodontal diseases. Periodontol 2000 2005: 38: 33–62. Slots J, Contreras A. Herpesviruses: a unifying causative factor in periodontitis? Oral Microbiol Immunol 2000: 12: 390–396. 25. Slots J, Saygun I, Sabeti M, Kubar A. Epstein-Barr virus in oral diseases. J Periodontal Res 2006: 41: 235–244. 26. Söder PÖ, Söder B, Nowak J, Jogestrand T. Early carotid atherosclerosis in subjects with periodontal diseases. Stroke 2005: 36: 1195–1200. 27. Stamm JW. Periodontal diseases and human health: new directions in periodontal medicine. Ann Periodontol 1998: 3: 1–2. 28. Udagawa N, Sato N, Yang S, Nakamura M, Yamashita T, Nakamura H, Noguchi T. Signal transduction of lipopolysaccharide-induced osteoclast differentiation. Periodontol 2000 2006: 43: 56–64. 29. Yoshie H, Kobayashi T, Tai H, Galicia JC. The role of genetic polymorphisms in periodontitis. Periodontol 2000 2006: 43: 102–132. 13