Denis F Kinane

Denis F Kinane
Universität Bern | UniBe · School of Dental Medicine

BDS, PhD, FDS RCS, FDS RCPS

About

281
Publications
83,027
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18,184
Citations
Citations since 2017
15 Research Items
7247 Citations
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201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
201720182019202020212022202305001,0001,500
Introduction
Denis F Kinane currently works at the University of Geneva as Professor ordainaire within the Periodontal Division and previously was at the Department of Pathology, and Department of Periodontology, and the Department of Otorhinolaryngology, University of Pennsylvania. Denis does research in the Cell Biology of Inflammation. Their most recent publication is 'in Nature Primers: Periodontal Disease Primer and Predictive diagnostic tests in periodontal diseases'.
Additional affiliations
January 2018 - present
University of Geneva
Position
  • Professor (Full)
July 2009 - December 2017
University of Pennsylvania
Position
  • Head of Faculty
June 2002 - June 2009
University of Louisville
Position
  • Center Director

Publications

Publications (281)
Article
Full-text available
DNA methylation controls several inflammatory genes affecting bone homeostasis. Hitherto, inhibition of DNA methylation in vivo in the context of periodontitis and osteoclastogenesis has not been attempted. Ligature-induced periodontitis in C57BL/6J mice was induced by placing ligature for five days with Decitabine (5-aza-2′-deoxycytidine) (1 mg/kg...
Article
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The role of the adaptor molecule MyD88 is thought to be independent of Toll-like receptor 3 (TLR3) signaling. In this report, we demonstrate a previously unknown role of MyD88 in TLR3 signaling in inducing endogenous ligands of TLR2 to elicit innate immune responses. Of the various TLR ligands examined, the TLR3-specific ligand polyinosinic:polycyt...
Article
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In aggressive periodontitis, the dysbiotic microbial community in the subgingival crevice, which is abundant in Aggregatibacter actinomycetemcomitans, interacts with extra- and intracellular receptors of host cells, leading to exacerbated inflammation and subsequent tissue destruction. Our goal was to understand the innate immune interactions of A....
Article
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Aim The purpose of this study was to determine inflammatory and epigenetic features following induction of oral and gut dysbiosis in experimental periodontitis in order to examine the interplay between oral and systemic infection. Materials and Methods Periodontitis was induced in 6‐ to 8‐wk‐old C57BL/6 mice by: 1) ligature placement (Lig group) (...
Article
The oral cavity is home for a plethora of bacteria and viruses. Epithelial barriers encounter these micro-organisms and recognize them via pathogen recognition receptors (PRRs) that instigate antibacterial and antiviral responses. We and others have shown that human gingival epithelial cells (HGECs) express PRRs to defend invading pathogens. Among...
Article
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Purpose of the Review The purpose is to provide current knowledge and recent development and understanding of periodontal disease dysbiosis in the perspective of epigenetic changes. Epigenetic changes, where environmental factors modify the gene expression network without changing the DNA sequence, may influence inflammatory diseases such as chroni...
Article
Polymorphonuclear neutrophils (PMNs) are indispensable in fighting infectious microbes by adopting various antimicrobial strategies including phagocytosis and neutrophil extracellular traps (NETs). Although the role and importance of PMNs in periodontal disease are well established, the specific molecular mechanisms involved in NET formation are ye...
Article
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MicroRNAs are small functional RNAs that modulate various biological processes in cells by interfering with gene translation. We have previously demonstrated that certain miRNAs play a crucial role in the innate immune responses of human oral epithelial cells to Porphyromonas gingivalis. While addressing the mechanisms of P. gingivalis induced apop...
Article
Epidemiological investigations support a ®rm relationship between smoking and periodontal disease. The likely bene®ts of smoking cessation programmes are considerable for periodontal disease, cancers and nearly all chronic systemic diseases. The mechanisms by which smoking may in¯uence the development and progression of periodontal disease are as y...
Article
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The “Biofilms, Microbiomes and Oral Diseases: Challenges and Future Perspectives” symposium jointly organized by Penn Dental Medicine and West China School of Stomatology was held on 30 September 2017 at Penn Wharton China Center (PWCC) in Beijing, China. The topics included the pathogenicity of oral biofilms, novel strategies for the control of bi...
Article
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A new periodontitis classification scheme has been adopted, in which forms of the disease previously recognized as “chronic” or “aggressive” are now grouped under a single category (“periodontitis”) and are further characterized based on a multi‐dimensional staging and grading system. Staging is largely dependent upon the severity of disease at pre...
Article
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Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth (the gingiva, bone and periodontal ligament), which could lead to tooth loss and contribute to systemic inflammation. Chronic periodontitis predominantly affects adults, but aggressive periodontitis may occasionally occur in chil...
Article
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Objectives The serum IL-17A:IL-17E ratio has previously been demonstrated to be a clinical marker of periodontitis. The aim of this study was to determine the effects of non-surgical periodontal treatment on the serum IL-17A:IL-17E ratio. Materials and methods Forty chronic periodontitis patients completed this study and received periodontal treatm...
Article
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Interleukin-8 (IL-8) gene polymorphisms have been considered as susceptibility factors in periodontal disease. However, the functional roles of IL-8 gene haplotypes have not been investigated. Here, we demonstrate for the first time the use of the CRISPR/Cas9 system to engineer the IL-8 gene, and tested the functionality of different haplotypes. Tw...
Article
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Periodontitis affects a subset of the population and our current thinking is that progression of periodontal disease may be either continuous or episodic. These features make diagnostic tools for disease status and progression assessment desirable in the management of this disease. Although many potential markers exist, several difficulties hamper...
Article
B-lineage cells (B lymphocytes and plasma cells) predominate in the inflammatory infiltrate of human chronic periodontitis. However, their role in disease pathogenesis and the factors responsible for their persistence in chronic lesions are poorly understood. In this regard, two cytokines of the TNF ligand superfamily, a proliferation-inducing liga...
Article
Bacteremia and systemic inflammatory markers are associated with periodontal and systemic diseases and may be linking mechanisms between these conditions. We hypothesized that in the development of gingival inflammation, systemic markers of inflammation and bacteremia would increase. To study the effect of bacteremia on systemic inflammatory marker...
Article
Periodontitis is a common chronic inflammatory disease that is initiated by a complex microbial biofilm that poses significant health and financial burdens globally. Porphyromonas gingivalis is a predominant pathogen that maintains chronic inflammatory periodontitis. Toll-like receptors (TLRs) play an important role in periodontitis by recognizing...
Conference Paper
Full-text available
With the advent of an increased emphasis on the potential to utilize biomarkers in saliva for systemic diseases, the issue of existing oral disease is an important consideration that could adversely affect the interpretation of diagnostic results obtained from saliva. We addressed the question does a patient’s oral inflammation status confound biom...
Article
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The comparative utility of serum and saliva as diagnostic fluids for identifying biomarkers of acute myocardial infarction (AMI) was investigated. The goal was to determine if salivary biomarkers could facilitate a screening diagnosis of AMI, especially in cases of non-ST elevation MI (NSTEMI), since these cases are not readily identified by electr...
Conference Paper
Epithelial recognition of P. gingivalis through TLR2 is crucial in mounting the innate immune response to counter bacterial attack in the human gingiva. However, in certain patients, gingival epithelial cells become dysfunctional creating abrogated epithelial inflammatory and antimicrobial response that may contribute to periodontal disease suscept...
Conference Paper
Hydrastis canadensis L. also known as “golden seal” is used to treat skin infections. The use of this herb in oral infections particularly against periodontitis is being explored. Objective: The aim was to test the anti-microbial and anti-inflammatory properties of H. canadensis aqueous extract (HC) against Porphyromonas gingivalis (Pg) and primary...
Article
Full-text available
P. gingivalis is a prominent periodontal pathogen that has potent effects on host cells. In this study we challenged gingival epithelial cells with P. gingivalis with the aim of assessing how mRNA levels of key target genes were modulated by P. gingivalis via the transcription factors FOXO1 and FOXO3. Primary mono- and multi-layer cultures of gingi...
Article
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This cross-sectional case-control study was conducted to provide a comparative evaluation of clinical periodontal measurements, together with serum levels of certain bioactive peptides and inflammatory cytokines, in relation to obesity. For this purpose, clinical periodontal measurements and the levels of serum leptin, adiponectin, interleukin-6 (I...
Article
Anti-citrullinated protein antibody (ACPA) responses may precede clinical onset of rheumatoid arthritis. Porphyromonas gingivalis peptidylarginine deiminase can citrullinate proteins possibly inducing autoimmunity in susceptible individuals. To determine whether periodontitis, carriage of P. gingivalis, smoking and periodontal therapy influence ACP...
Article
To evaluate clinical outcomes and effects of non-surgical periodontal therapy on serum, gingival crevicular fluid (GCF) interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α) levels in chronic periodontitis patients with/without rheumatoid arthritis (RA), fifteen RA patients with chronic periodontitis (RA-P) and 15 systemically healthy n...
Conference Paper
Objective: To determine whether oral health status confounds biomarker levels used in the assessment of myocardial infarction (MI). Methods: A cross-sectional clinical study was implemented where oral health status was determined and serum and unstimulated whole saliva (UWS) were obtained from 92 MI patients (<48 hours of chest pain onset) and 11...
Conference Paper
Porphyromonas gingivalis is a Gram –ve anaerobe that initiates periodontitis. As a first line of defense against pathogen attack, human gingival epithelial cells (HGECs) secrete antimicrobial peptides, chemokines and pro-inflammatory cytokines including Interleukin-7. IL-7 is a growth factor cytokine and crucial in lymphocyte homeostasis during inf...
Conference Paper
Objective: B Lymphocyte Stimulator (BLYS) and ‪A PRoliferation-Inducing Ligand (APRIL) are members of the TNF-alpha superfamily that are involved in the induction of B cell proliferation/differentiation and maintenance of plasma cell survival, respectively. The predominance of plasma cells in chronic periodontitis lesions suggests that these mole...
Conference Paper
Pathogen mediated gain of epigenetic reprogramming in humans is recently being implicated in cancer and immune mediated diseases. Periodontitis is an immune mediated disease instigated by a biofilm pathogen Porphyromonas gingivalis. The host innate immune system recognizes P. gingivalis through TLR2/4. Nevertheless, P. gingivalis induced epigenetic...
Article
A gingival crevice model (epithelial cell-Porphyromonas gingivalis-neutrophil) was established and used to profile gingipain, matrix metalloproteinase (MMP), MMP mediators [neutrophil gelatinase-associated lipocalin (NGAL) and tissue inhibitor of metalloproteinases 1 (TIMP-1)] and cytokine networks. Smoking is the primary environmental risk factor...
Conference Paper
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Objectives: To evaluate whether oral swabbing with 0.2% chlorhexidine gluconate (CHX) decreases risk of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients. Methods: 61 dentate patients scheduled for invasive mechanical ventilation for at least 48 hours were included in this randomized, double-blind, controlled study. As t...
Conference Paper
Objective: Porphyromonas gingivalis, a Gram-negative oral pathogen has been shown to induce apoptosis in human gingival epithelial cells, yet the underlining cellular mechanisms controlling this process are poorly understood. We hypothesized that ‘P. gingivalis induced apoptosis’ is mediated through degradation of actin by gingipains inducing cyt...
Conference Paper
Objective: Systemic inflammation is common in obese individuals with elevated levels of inflammatory cytokines such as TNF-a and IL-6 accompanied by high levels of acute phase proteins such as CRP. These inflammatory mediators are commonly considered as sequelae to periodontal disease. This project is part of a larger study aimed at determining rel...
Conference Paper
Objective: Having identified TLR3 as one of the important receptors in primary gingival epithelial cells inflammation, we hypothesized that its downstream signalling may control other TLRs expression and require Myd88 for proinflammatory cytokines expression. Method: To test this hypothesis, we utilized primary human gingival epithelial cells (HG...
Article
Porphyromonas gingivalis, a Gram-negative oral pathogen, has been shown to induce apoptosis in human gingival epithelial cells, yet the underlining cellular mechanisms controlling this process are poorly understood. We have previously shown that the P. gingivalis proteases arginine and lysine gingipains, are necessary and sufficient to induce host...
Article
The aim was to evaluate whether oral swabbing with 0.2% chlorhexidine gluconate (CHX) decreases the risk of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients. Sixty-one dentate patients scheduled for invasive mechanical ventilation for at least 48 h were included in this randomized, double-blind, controlled study. As these...
Article
This chapter addresses the host responses to the microbial biofilm that constitutes the subgingival dental plaque. The host response to infection draws upon the innate, inflammatory and adaptive immune systems, whose role is to provide the appropriate response to the offending microorganisms. In some cases, this will be little or no response when e...
Article
To characterize and map temporal changes in the biological and clinical phenotype during a 21-day experimental gingivitis study. Experimental gingivitis was induced over 21 days in healthy human volunteers (n = 56), after which normal brushing was resumed (resolution phase). Gingival and plaque indices were assessed. Gingival crevicular fluid was c...
Book
Our understanding of the etiopathology of periodontal disease has changed greatly over the last decade. The huge diversity of species within the microbial biofilm and the enormous multi-layered complexity of the innate, inflammatory and adaptive immune responses generated in response to it warrant study and discussion. Comprising reviews from renow...
Article
Activation of the Akt pathway plays a pivotal role in regulating the inflammatory response. Rictor is a component of the mTORC2 complex, and its loss has been shown to abrogate the phosphorylation of Akt at serine 473. However, the biological importance of mTORC2 in innate immunity is currently unknown. Here we demonstrate that rictor plays a criti...
Conference Paper
Recent studies implicate the mammalian target of rapamycin (mTOR) pathway in the control of inflammatory responses following Toll-like receptors (TLRs) stimulation in myeloid cells but its role in non-myeloid cells such as human gingival epithelial cells is unknown. Objective: Our objective was to unravel the role of mTOR and its signaling in non-m...
Conference Paper
Porphyromonas gingivalis is a Gram-negative anaerobe of dental plaque and a putative pathogen in chronic periodontitis. Recently our group demonstrated the induction of apoptosis by P. gingivalis in human gingival epithelial cells (HGECs) or oral keratinocytes through gingipain dependent manner (Stathopoulou et. al. BMC Microbiol. 2009 May 27;9:107...
Conference Paper
Toll like receptors are germ line encoded receptors that play a key role in innate immunity. Human Gingival Epithelial Cells (HGECs) forms first line of defense against plaque bacteria and viruses in the oral cavity. Analyzing the expression of TLRs and its signaling networks in HGECs becomes important in understanding periodontal disease pathogene...
Article
This study compared total NIH research funding across US dental institutions from 2005 to 2009. Utilizing the online NIH RePORT, we obtained comprehensive award data for US dental schools by funding NIH Institutes/Centers (ICs). Fifty dental schools were awarded a total of $974.393 million, 69.3% from NIDCR and 30.7% from 21 other ICs. These provid...
Article
Sanz M, Lang NP, Kinane DF, Berglundh T, Chapple I, Tonetti MS. Seventh European Workshop on Periodontology of the European Academy of Periodontology at the Parador at La Granja, Segovia, Spain. J Clin Periodontol 2011; 38 (Suppl. 11): 1-2. doi: 10.1111/j.1600-051X.2010.01692.x.
Article
A major challenge in clinical periodontics is to find a reliable molecular marker of periodontal tissue destruction with high sensitivity, specificity and utility. The aim of this systematic review is to evaluate available literature on 'the utility of molecular markers of soft and hard periodontal tissue destruction'. Based on the focused question...
Article
Major challenges in periodontology include understanding the pathophysiology, the interplay between various components of the host response, parallels with other diseases and identifying biomarkers of the disease. Four reviews were compiled with the aim of better understanding: (1) the role of polymorphic nuclear leucocytes (PMNs), i.e. neutrophils...
Article
To evaluate initial periodontal treatment effects on gingival crevicular fluid (GCF) interleukin-6 (IL-6), tissue-type plasminogen activator (tPA), plasminogen activator inhibitor-2 (PAI-2), albumin levels in type 2 diabetic patients. GCF samples were collected from 20 type 2 diabetic, 22 non-diabetic non-smokers all with chronic periodontitis at b...
Article
The ability of IFN-β to induce IL-10 production from innate immune cells is important for its anti-inflammatory properties and is believed to contribute to its therapeutic value in treating multiple sclerosis patients. In this study, we identified that IFN-β stimulates IL-10 production by activating the JAK1- and PI3K-signaling pathways. JAK1 activ...
Conference Paper
Adiponectin is one of a group of adipokines produced by adipose cells and is considered an anti-inflammatory molecule. In contrast, C-reactive protein has been identified as a hallmark of systemic inflammation and used as a risk marker of cardiovascular risk and disease. Objectives: We hypothesized a differential response in these biomolecules in t...
Article
Full-text available
Host defense against invading pathogens is triggered by various receptors including toll-like receptors (TLRs). Activation of TLRs is a pivotal step in the initiation of innate, inflammatory, and antimicrobial defense mechanisms. Human beta-defensin 2 (HBD-2) is a cationic antimicrobial peptide secreted upon gram-negative bacterial perturbation in...
Conference Paper
Objective: The utility of saliva as an alternative diagnostic fluid for identifying biomarkers of acute myocardial infarction (AMI) was investigated using classification and regression tree (CART). Methods: Serum and unstimulated whole saliva (UWS) from 80 AMI patients obtained <48 hours of chest pain onset and 85 asymptomatic healthy controls were...
Conference Paper
Objectives: We set out to determine the influence of cigarette smoke extract (CSE) on cytokine and protease networks produced in a novel model of mucosal inflammation representing the mucosal surface (primary human gingival epithelial cells; HGECs); the major overlying sulcular immune infiltrate (primary human neutrophils; PMNs) and a relevant infl...
Article
The comparison of the efficacy of surgical and nonsurgical procedures revealed that scaling and root planing alone or in combination with flap procedures are effective methods for the treatment of chronic periodontitis. Also, the consistent message is that in treating deep pockets, open-flap debridement results in greater probing pocket depth reduc...
Article
Full-text available
This study was performed to evaluate the effects of initial periodontal treatment on clinical periodontal measurements, glycemic control, and systemic inflammatory mediator levels in patients with type 2 diabetes and chronic periodontitis. Thirteen well-controlled (glycated hemoglobin [HbA1c] <7%) and 12 poorly controlled (HbA1c > or =7%) patients...
Article
Full-text available
The dental plaque is comprised of numerous bacterial species, which may or may not be pathogenic. Human gingival epithelial cells (HGECs) respond to perturbation by various bacteria of the dental plaque by production of different levels of inflammatory cytokines, which is a putative reflection of their virulence. The aim of the current study was to...
Article
Full-text available
Microbial biofilms are known to cause an increasing number of chronic inflammatory and infectious conditions. A classical example is chronic periodontal disease, a condition initiated by the subgingival dental plaque biofilm on gingival epithelial tissues. We describe here a new model that permits the examination of interactions between the bacteri...
Article
In recent years, there has been a dramatic shift in the overall oral health status of populations in the developed world: people are living longer and retaining more natural teeth into old age. While this can be viewed as a sign of improvement, this situation brings its own problems. The prevalence of caries, enamel erosion and chronic periodontal...
Article
In recent years, there has been a dramatic shift in the overall oral health status of populations in the developed world: people are living longer and retaining more natural teeth into old age. While this can be viewed as a sign of improvement, this situation brings its own problems. The prevalence of caries, enamel erosion and chronic periodontal...
Article
IL-12p70 is an immunoregulatory cytokine that has been shown to induce IL-10 production from CD4+ T cells, yet the underlying cellular mechanisms controlling this process are poorly understood. In the present study, we demonstrate that IL-12p70 induces IL-10 production from human memory CD4+ T cells via a PI3K-dependent signaling mechanism. Specifi...
Article
Full-text available
The purpose of this study was to evaluate and compare salivary concentrations of reduced, oxidized glutathione, uric acid, ascorbic acid, and total antioxidant capacity in subjects with diabetes and systemically healthy subjects with inflammatory periodontal disease. Sixteen patients with type 1 diabetes mellitus (DM), 25 patients with type 2 DM, a...
Article
Full-text available
For adults with chest pain, the electrocardiogram (ECG) and measures of serum biomarkers are used to screen and diagnose myocardial necrosis. These measurements require time that can delay therapy and affect prognosis. Our objective was to investigate the feasibility and utility of saliva as an alternative diagnostic fluid for identifying biomarker...
Article
Kinane DF, Hajishengallis G. Polymicrobial infections, biofilms, and beyond. J Clin Periodontol 2009; 36: 404–405 doi: 10.1111/j.1600-051X.2009.01396.x.
Article
Full-text available
Mammalian biological processes such as inflammation, involve regulation of hundreds of genes controlling onset and termination. MicroRNAs (miRNAs) can translationally repress target mRNAs and regulate innate immune responses. Our model system comprised primary human keratinocytes, which exhibited robust differences in inflammatory cytokine producti...
Article
In the pathogenesis of chronic inflammatory periodontal disease, neutrophils are recognized as a major cellular component from the histopathology of the periodontal lesion around teeth and from clinical cases where absence or dysfunction of neutrophils results in major periodontal destruction. Neutrophils are recruited in vast numbers into the ging...
Conference Paper
Objectives: Chronic inflammatory periodontal disease is initiated by the dental plaque biofilm's perturbation of the gingival tissues. The epithelium lining the gingival crevice is in juxtaposition to the subgingival plaque biofilm. We aimed to develop a model that incorporated this eukaryotic:prokaryotic cell interaction by co-culturing primary hu...
Conference Paper
Objectives: The general aim is to model the mutual interactions between an artificial subgingival biofilm formed in vitro by 10 species and primary human gingival epithelial cells (HGEC). This presentation addresses the creation of the biofilm. Methods: The in vitro subgingival plaque model is an advancement of the 6-species Zrich biofilm model des...
Conference Paper
Objectives: Gingival epithelium provides the first line of defense against oral pathogens. Neutrophils are the most abundant immune cells recruited to the early inflammatory lesion and the most numerous host cells within the periodontal tissues. The aim of this study is to determine how neutrophils modulate the initial responses of primary human gi...
Conference Paper
Background: Periodontitis is currently diagnosed almost entirely on gross clinical manifestations, i.e., signs of gingival inflammation such as redness and bleeding on probing, periodontal pocketing, and periodontal attachment or alveolar bone loss. It is generally agreed such parameters do not reliably identify susceptible individuals or distingui...
Conference Paper
Objective: To assess the role of Sphingosine kinase 1 (SPHK1) and GSK3-β in the regulation of human beta defensin 2 (HBD2), an antimicrobial peptide produced by oral gingival keratinocytes. Methods: Primary human gingival epithelial cells (HGECs) were challenged with heat inactivated Porphyromonas gingivalis and a variety of Toll-Like Receptor (T...
Article
Clinical studies indicate that primary proinflammatory cytokines, such as interleukin-1beta (IL-1beta) are elevated in the gingival crevice around teeth with periodontitis but the secondary cytokines and chemokines, IL-6 and IL-8, are not. The human gingival epithelial cells (HGECs) lining the gingival sulcus respond to perturbation by microbes of...
Article
IL-1 receptor antagonist (IL-1Ra), a natural inhibitor of IL-1beta, has been shown to regulate the progression of a variety of inflammatory diseases. Although experimental studies and clinical trials have demonstrated the importance of IL-1Ra in chronic inflammatory diseases, the cellular mechanisms responsible for regulating the endogenous product...