Principles of Periodontology

Periodontal diseases are among the most common diseases affecting humans. Dental biofilm is a contributor to the etiology of most periodontal diseases. It is also widely accepted that immunological and inflammatory responses to biofilm components are manifested by signs and symptoms of periodontal disease. The outcome of such interaction is modulated by risk factors (modifiers), either inherent (genetic) or acquired (environmental), significantly affecting the initiation and progression of different periodontal disease phenotypes. While definitive genetic determinants responsible for either susceptibility or resistance to periodontal disease have yet to be identified, many factors affecting the pathogenesis have been described, including smoking, diabetes, obesity, medications, and nutrition. Currently, periodontal diseases are classified based upon clinical disease traits using radiographs and clinical examination. Advances in genomics, molecular biology, and personalized medicine may result in new guidelines for unambiguous disease definition and diagnosis in the future. Recent studies have implied relationships between periodontal diseases and systemic conditions. Answering critical questions regarding host‐parasite interactions in periodontal diseases may provide new insight in the pathogenesis of other biomedical disorders. Therapeutic efforts have focused on the microbial nature of the infection, as active treatment centers on biofilm disruption by non‐surgical mechanical debridement with antimicrobial and sometimes anti‐inflammatory adjuncts. The surgical treatment aims at gaining access to periodontal lesions and correcting unfavorable gingival/osseous contours to achieve a periodontal architecture that will provide for more effective oral hygiene and periodontal maintenance. In addition, advances in tissue engineering have provided innovative means to regenerate/repair periodontal defects, based upon principles of guided tissue regeneration and utilization of growth factors/biologic mediators. To maintain periodontal stability, these treatments need to be supplemented with long‐term maintenance (supportive periodontal therapy) programs

Bleomycin and IL-1β–mediated pulmonary fibrosis is IL-17A dependent

Idiopathic pulmonary fibrosis (IPF) is a destructive inflammatory disease with limited therapeutic options. To better understand the inflammatory responses that precede and concur with collagen deposition, we used three models of pulmonary fibrosis and identify a critical mechanistic role for IL-17A. After exposure to bleomycin (BLM), but not Schistosoma mansoni eggs, IL-17A produced by CD4+ and γδ+ T cells induced significant neutrophilia and pulmonary fibrosis. Studies conducted with C57BL/6 il17a−/− mice confirmed an essential role for IL-17A. Mechanistically, using ifnγ−/−, il10−/−, il10−/−il12p40−/−, and il10−/−il17a−/− mice and TGF-β blockade, we demonstrate that IL-17A–driven fibrosis is suppressed by IL-10 and facilitated by IFN-γ and IL-12/23p40. BLM-induced IL-17A production was also TGF-β dependent, and recombinant IL-17A–mediated fibrosis required TGF-β, suggesting cooperative roles for IL-17A and TGF-β in the development of fibrosis. Finally, we show that fibrosis induced by IL-1β, which mimics BLM-induced fibrosis, is also highly dependent on IL-17A. IL-17A and IL-1β were also increased in the bronchoalveolar lavage fluid of patients with IPF. Together, these studies identify a critical role for IL-17A in fibrosis, illustrating the potential utility of targeting IL-17A in the treatment of drug and inflammation-induced fibrosis

The Porphyromonas gingivalis/host interactome shows enrichment in GWASdb genes related to Alzheimer’s disease, diabetes and cardiovascular diseases

Periodontal disease is of established aetiology in which polymicrobial synergistic ecology has become dysbiotic under the influence of Porphyromonas gingivalis. Following breakdown of the host’s protective oral tissue barriers, P. gingivalis migrates to developing inflammatory pathologies that associate with Alzheimer’s disease (AD). Periodontal disease is a risk factor for cardiovascular disorders (CVD), type II diabetes mellitus (T2DM), AD and other chronic diseases, whilst T2DM exacerbates periodontitis. This study analysed the relationship between the P. gingivalis/host interactome and the genes identified in genome-wide association studies (GWAS) for the aforementioned conditions using data from GWASdb (P<1E-03) and, in some cases, from the NCBI/EBI GWAS database (P< 1E-05). Gene expression data from periodontitis or P. gingivalis microarray was compared to microarray datasets from the AD hippocampus and/or from carotid artery plaques. The results demonstrated that the host genes of the P. gingivalis interactome were significantly enriched in genes deposited in GWASdb genes related to cognitive disorders, AD and dementia, and its co-morbid conditions T2DM, obesity, and CVD. The P. gingivalis/host interactome was also enriched in GWAS genes from the more stringent NCBI-EBI database for AD, atherosclerosis and T2DM. The misregulated genes in periodontitis tissue or P. gingivalis infected macrophages also matched those in the AD hippocampus or atherosclerotic plaques. Together, these data suggest important gene/environment interactions between P. gingivalis and susceptibility genes or gene expression changes in conditions where periodontal disease is a contributory factor

Effects of Aging on Endotoxin Tolerance Induced by Lipopolysaccharides Derived from Porphyromonas gingivalis and Escherichia coli

Background: Periodontitis is a bacterially induced chronic inflammatory disease. Exposure of the host to periodontal pathogens and their virulence factors induces a state of hyporesponsiveness to subsequent stimulations, termed endotoxin tolerance. Aging has a profound effect on immune response to bacteria challenge. The aim of this study was to explore the effects of aging on endotoxin tolerance induced by Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and Escherichia coli (E. coli) LPS in murine peritoneal macrophages. Methodology/Principal Findings: We studied the cytokine production (TNF-aand IL-10) and Toll-like receptor 2, 4 (TLR2, 4) gene and protein expressions in peritoneal macrophages from young (2-month-old) and middle-aged (12-month-old) ICR mice following single or repeated P. gingivalis LPS or E. coli LPS stimulation. Pretreatment of peritoneal macrophages with P. gingivalis LPS or E. coli LPS resulted in a reduction in TNF-a production and an increase in IL-10 production upon secondary stimulation (p,0.05), and the markedly lower levels of TNF-a and higher levels of IL-10 were observed in macrophages from young mice compared with those from middle-aged mice (p,0.05). In addition, LPS restimulations also led to the significantly lower expression levels of TLR2, 4 mRNA and protein in macrophages from young mice (p,0.05). Conclusions/Significance: Repeated LPS stimulations triggered endotoxin tolerance in peritoneal macrophages and the ability to develop tolerance in young mice was more excellent. The impaired ability to develop endotoxin tolerance resulte

Immunomodulatory effects of tick saliva on dermal cells exposed to \u3cem\u3eBorrelia burgdorferi\u3c/em\u3e, the agent of Lyme disease

Background: The prolonged feeding process of ixodid ticks, in combination with bacterial transmission, should lead to a robust inflammatory response at the blood-feeding site. Yet, factors present in tick saliva may down-regulate such responses, which may be beneficial to spirochete transmission. The primary goal of this study was to test the hypothesis that tick saliva, in the context of Borrelia burgdorferi, can have widespread effects on the production of immune mediators in skin. Methods: A cross-section of tick feeding on skin was examined histologically. Human THP-1 cells stimulated with B. burgdorferi and grown in the presence or absence of tick saliva were examined by human DNA microarray, cytokine bead array, sandwich ELISA, and qRT-PCR. Similar experiments were also conducted using dermal fibroblasts. Results: Tick feeding on skin showed dermal infiltration of histiocytes and granulocytes at the bite location. Changes in monocytic transcript levels during co-culture with B. burgdorferi and saliva indicated that tick saliva had a suppressive effect on the expression of certain pro-inflammatory mediators, such as IL-8 (CXCL8) and TLR2, but had a stimulatory effect on specific molecules such as the Interleukin 10 receptor, alpha subunit (IL-10RA), a known mediator of the immunosuppressive signal of IL-10. Stimulated cell culture supernatants were analyzed via antigen-capture ELISA and cytokine bead array for inflammatory mediator production. Treatment of monocytes with saliva significantly reduced the expression of several key mediators including IL-6, IL-8 and TNF-alpha. Tick saliva had an opposite effect on dermal fibroblasts. Rather than inhibiting, saliva enhanced production of pro-inflammatory mediators, including IL-8 and IL-6 from these sentinel skin cells. Conclusions: The effects of ixodid tick saliva on resident skin cells is cell type-dependent. The response to both tick and pathogen at the site of feeding favors pathogen transmission, but may not be wholly suppressed by tick saliva

Biological foundation for periodontitis as a potential risk factor for atherosclerosis

Links between periodontal diseases and systemic diseases have been well documented by epidemiological studies. Recently, research has shifted to elucidating the biologic mechanism for a causal relationship. One focus of interest is atherosclerosis, the underlying event of cardiovascular diseases due to its serious health impact. However, it is still not clear whether periodontopathic pathogens are truly etiologic agents or ubiquitous bystanders. This article reviews the current understanding about the molecular biological interactions between periodontal disease and atherosclerosis and the biological plausibility of periodontitis as a potential risk factor for cardiovascular disease. Materials and methods:  The current literature regarding periodontal diseases and atherosclerosis and coronary vascular disease was searched using the Medline and PubMed databases. Results:  In vitro experiments and animal models are appropriate tools to investigate the biological interactions between periodontal disease and atherosclerosis at the cell molecular level. The concepts linking both pathologies refer to inflammatory response, immune responses, and hemostasis. In particular, Porphyromonas gingivalis appears to have unique, versatile pathogenic properties. Whether or not these findings from isolated cells or animal models are applicable in humans with genetic and environmental variations is yet to be determined. Likewise, the benefit from periodontal therapy on the development of atherosclerosis is unclear. Approaches targeting inflammatory and immune responses of periodontitis and atherosclerosis simultaneously are very intriguing. Conclusion:  An emerging concept suggests that a pathogenic burden from different sources might overcome an individual threshold culminating in clinical sequela. P. gingivalis contributes directly and indirectly to atherosclerosis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66109/1/j.1600-0765.2004.00771.x.pd