Abstract
Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Furthermore hyperlipidemic mice deficient in TLR2, TLR4, and MyD88 signaling exhibit diminished inflammatory responses and decreased atherosclerosis. Accumulating evidence has implicated specific infectious agents including the periodontal disease pathogen Porphyromonas gingivalis in the progression of atherosclerosis. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen P. gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. We have established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate immune signaling in the context of local and distant chronic inflammation induced by this pathogen. We have demonstrated that P. gingivalis requires TLR2 to induce oral inflammatory bone lose in mice. Furthermore, we have demonstrated that P. gingivalis infection accelerates atherosclerosis in hyperlipidemic mice with an associated increase in expression of TLR2 and TLR4 in atherosclerotic lesions. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. Improved understanding of the mechanisms driving infection, and chronic inflammation during atherosclerosis may ultimately provide new targets for therapy.
Keywords: Atherosclerosis, Inflammation, Periodontal disease, P. gingivalis, TLR2, TLR4, Endothelial cells, Macrophages
Current Pharmaceutical Design
Title: Porphyromonas gingivalis Mediated Periodontal Disease and Atherosclerosis:Disparate Diseases with Commonalities in Pathogenesis Through TLRs
Volume: 13 Issue: 36
Author(s): Frank C. Gibson III and Caroline A. Genco
Affiliation:
Keywords: Atherosclerosis, Inflammation, Periodontal disease, P. gingivalis, TLR2, TLR4, Endothelial cells, Macrophages
Abstract: Toll-like receptors (TLRs) are a group of pathogen-associated molecular pattern receptors, which play an important role in innate immune signaling in response to microbial infection. It has been demonstrated that TLRs are differentially up regulated in response to microbial infection and chronic inflammatory diseases such as atherosclerosis. Furthermore hyperlipidemic mice deficient in TLR2, TLR4, and MyD88 signaling exhibit diminished inflammatory responses and decreased atherosclerosis. Accumulating evidence has implicated specific infectious agents including the periodontal disease pathogen Porphyromonas gingivalis in the progression of atherosclerosis. Evidence in humans suggesting that periodontal infection predisposes to atherosclerosis is derived from studies demonstrating that the periodontal pathogen P. gingivalis resides in the wall of atherosclerotic vessels and seroepidemiological studies demonstrating an association between pathogen-specific IgG antibodies and atherosclerosis. We have established that the inflammatory signaling pathways that P. gingivalis utilizes is dependent on the cell type and this specificity clearly influences innate immune signaling in the context of local and distant chronic inflammation induced by this pathogen. We have demonstrated that P. gingivalis requires TLR2 to induce oral inflammatory bone lose in mice. Furthermore, we have demonstrated that P. gingivalis infection accelerates atherosclerosis in hyperlipidemic mice with an associated increase in expression of TLR2 and TLR4 in atherosclerotic lesions. Our recent work with P. gingivalis has demonstrated the effectiveness of specific intervention strategies (immunization) in the prevention of pathogen-accelerated atherosclerosis. Improved understanding of the mechanisms driving infection, and chronic inflammation during atherosclerosis may ultimately provide new targets for therapy.
Export Options
About this article
Cite this article as:
Gibson III C. Frank and Genco A. Caroline, Porphyromonas gingivalis Mediated Periodontal Disease and Atherosclerosis:Disparate Diseases with Commonalities in Pathogenesis Through TLRs, Current Pharmaceutical Design 2007; 13 (36) . https://dx.doi.org/10.2174/138161207783018554
DOI https://dx.doi.org/10.2174/138161207783018554 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Clinical Applications of Non-Antimicrobial Actions of Tetracyclines in Inflammatory Diseases
Current Drug Therapy Neurodegenerative Diseases and Flavonoids: Special Reference to Kaempferol
CNS & Neurological Disorders - Drug Targets Green Tea from the Far East to the Drug Store: Focus on the Beneficial Cardiovascular Effects
Current Pharmaceutical Design Phytochemical Screening and In-Vitro Antibacterial and Anticancer Activity of Crude Extract of <i>Matricaria aurea</i>
Current Pharmaceutical Design Decoding the Structural Basis For Carbapenem Hydrolysis By Class A β-lactamases: Fishing For A Pharmacophore
Current Drug Targets Immune Frailty and Nanomaterials: The Case of Allergies
Current Bionanotechnology (Discontinued) The Nervous System as a Critical Regulator of Immune Responses Underlying Allergy
Current Pharmaceutical Design Applications of Microemulsion Based Drug Delivery System
Current Drug Delivery Influence of Polymorphic N-Acetyltransferases on Non-Malignant Spontaneous Disorders and on Response to Drugs
Current Drug Metabolism subject Index To Volume 2
Current Pharmaceutical Biotechnology Intestinal Microbiota: A Regulator of Intestinal Inflammation and Cardiac Ischemia?
Current Drug Targets Proteomics and Epigenetic Mechanisms in Stem Cells
Current Proteomics Stem Cell-Based Approaches for Intervertebral Disc Regeneration
Current Stem Cell Research & Therapy Gut Permeability and Microbiota in Parkinson’s Disease: Role of Depression, Tryptophan Catabolites, Oxidative and Nitrosative Stress and Melatonergic Pathways
Current Pharmaceutical Design Is the Treatment with Biological or Non-biological DMARDS a Modifier of Periodontal Condition in Patients with Rheumatoid Arthritis?
Current Rheumatology Reviews Development and Optimization of Sustained Release Moxifloxacin Hydrochloride Loaded Nanoemulsion for Ophthalmic Drug Delivery: A 3<sup>2</sup> Factorial Design Approach
Micro and Nanosystems Direct Modification of Bioactive Phenothiazines by Exposure to Laser Radiation
Recent Patents on Anti-Infective Drug Discovery Novel Anti-Cancer Strategy in Bone Tumors by Targeting Molecular and Cellular Modulators of Bone Resorption
Recent Patents on Anti-Cancer Drug Discovery Editorial [Hot Topic: Drug Metabolisms Associated with Human Microbiome (Guest Editor: Chun-Ming Huang) ]
Current Drug Metabolism Mesenchymal Stem/Stromal Cells: A New "Cells as Drugs" Paradigm. Efficacy and Critical Aspects in Cell Therapy
Current Pharmaceutical Design