Barros SP, Wirojchanasak S, Barrow DA, Panagakos F, Devizio W, Offenbacher S. Triclosan inhibition of acute and chronic inflammatory gene pathways. J Clin Periodontol 2010; 37: 412–418. doi: ...10.1111/j.1600‐051X.2010.01548.x.
Aim: We sought to determine whether triclosan (2,4,4′‐trichloro‐2′‐hydroxydiphenylether), an extensively used anti‐plaque agent with broad‐spectrum anti‐microbial activity, with reported anti‐inflammatory effects via inhibition of prostaglandin E2 and interleukin 1 (IL‐1)β, could also more broadly suppress multiple inflammatory gene pathways responsible for the pathogenesis of gingivitis and periodontitis.
Materials and Methods: As an exploratory study, the effects of triclosan on the inflammatory gene expression profile were assessed ex vivo using peripheral whole blood samples from eight periodontally healthy donors. Ten‐millilitres whole blood aliquots were incubated 2 h with 0.3 μg/ml Escherichia coli lipopolysaccharide (LPS) with or without 0.5 μg/ml triclosan. Affymetrix microarray gene expression profiles from isolated leucocytes and pathway‐specific quantitative polymerase chain reaction arrays were used to investigate changes in expression of target cytokines and cell signalling molecules.
Results: Ex vivo human whole blood assays indicated that triclosan significantly down‐regulated the LPS‐stimulated expression of Toll‐like receptor signalling molecules and other multiple inflammatory molecules including IL‐1 and IL‐6 and the dampening of signals that activate the T‐helper type 1 acquired immune response via suppression of CD70 with concomitant up‐regulation of growth factors related to bone morphogenetic protein (BMP)2 and BMP6 synthesis.
Conclusions: Anti‐inflammatory effects were found in this exploratory survey, including suppression of microbial‐pathogen recognition pathway molecules and the suppression of acute and chronic mediators of inflammation.
Background: To our knowledge, changes in the patterns of whole‐transcriptome gene expression that occur during the induction and resolution of experimental gingivitis in humans were not previously ...explored using bioinformatic tools.
Methods: Gingival biopsy samples collected from 14 subjects during a 28‐day stent‐induced experimental gingivitis model, followed by treatment, and resolution at days 28 through 35 were analyzed using gene‐expression arrays. Biopsy samples were collected at different sites within each subject at baseline (day 0), at the peak of gingivitis (day 28), and at resolution (day 35) and processed using whole‐transcriptome gene‐expression arrays. Gene‐expression data were analyzed to identify biologic themes and pathways associated with changes in gene‐expression profiles that occur during the induction and resolution of experimental gingivitis using bioinformatic tools.
Results: During disease induction and resolution, the dominant expression pathway was the immune response, with 131 immune response genes significantly up‐ or downregulated during induction, during resolution, or during both at P <0.05. During induction, there was significant transient increase in the expression of inflammatory and oxidative stress mediators, including interleukin (IL)‐1 alpha (IL1A), IL‐1 beta (IL1B), IL8, RANTES, colony stimulating factor 3 (CSF3), and superoxide dismutase 2 (SOD2), and a decreased expression of IP10, interferon inducible T‐cell alpha chemoattractant (ITAC), matrix metalloproteinase 10 (MMP10), and beta 4 defensin (DEFB4). These genes reversed expression patterns upon resolution in parallel with the reversal of gingival inflammation.
Conclusions: A relatively small subset (11.9%) of the immune response genes analyzed by array was transiently activated in response to biofilm overgrowth, suggesting a degree of specificity in the transcriptome‐expression response. The fact that this same subset demonstrates a reversal in expression patterns during clinical resolution implicates these genes as being critical for maintaining tissue homeostasis at the biofilm–gingival interface. In addition to the immune response pathway as the dominant response theme, new candidate genes and pathways were identified as being selectively modulated in experimental gingivitis, including neural processes, epithelial defenses, angiogenesis, and wound healing.
Epigenetics as a modifiable risk factor in periodontal diseases has been investigated in light of the current knowledge of how chronic infection and inflammation can affect gene‐specific epigenetic ...reprogramming in periodontal tissues. Epigenomic programming might be particularly sensitive to environmental influences, and a combination of physiological stressors and environmental exposures appears to affect the epigenomic program acquired by a cell during differentiation and throughout the cellular lineage lifespan. Viral and bacterial infections can establish several types of epigenetic modifications, which sometimes engage in a complex epigenetic crosstalk also reflecting in the establishment and progress of periodontal diseases. The inflammatory and metabolic states of the periodontal tissues are driven by the infectious stimuli, and the magnitude of the cellular and molecular signature response is further dictated by the host genetic and epigenetic traits associated with various systemic exposures, including smoking, obesity and diabetes/hyperglycemia. This review discusses the advances in epigenetics, focusing on the role of DNA methylation in the pathogenesis of periodontal disease and the potential of epigenetic therapy.
The third author, Zvi G. Loewy, was given the incorrect affiliation. Department of Pharmaceutical and Biomedical Sciences, Touro College of Pharmacy, New York, New York, United States of America and ...Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, New York, United States of America Citation: Barros SP, Suruki R, Loewy ZG, Beck JD, Offenbacher S (2013) Correction: A Cohort Study of the Impact of Tooth Loss and Periodontal Disease on Respiratory Events among COPD Subjects: Modulatory Role of Systemic Biomarkers of Inflammation.
Background: This study measures microbial composition changes during biofilm overgrowth and subsequent removal among patients with various states of periodontal disease.
Methods: In this prospective ...cohort study, 175 participants with various periodontal states (five biofilm‐gingival interface BGI groups) abstained from oral hygiene while using an acrylic stent. At day 21, participants reinstituted oral hygiene and were followed for 4 weeks. Clinical parameters were recorded, and subgingival plaque samples were analyzed at baseline, peak of induction (day 21), and resolution using 16S rRNA probes (human oral microbe identification microarray HOMIM). Using the change score (peak at induction minus baseline) for bleeding on probing and probing depth (PD), the patients were separated into high and low clinical responders.
Results: At baseline, synergistetes were more abundant in moderate and severe periodontitis (BGI‐P2 and ‐P3) compared to mild periodontitis (BGI‐P1), health (BGI‐H), and gingivitis (BGI‐G) (P = 0.005). Overall, at day 21 there was an increase in HOMIM scores of firmicutes (P ≤0.001), fusobacteria (P = 0.003), proteobacteria (P ≤0.001), synergistetes (P = 0.04), and bacteroidetes (P ≤0.001). At resolution, these phyla returned to baseline, except for synergistetes. Levels of synergistetes were significantly higher at day 21 (P ≤0.0001) and resolution (P = 0.0002) for high clinical responders compared to low responders.
Conclusion: The association of synergistetes as a baseline predictor of incident PD increase, as well as the higher levels at day 21, indicates a pathogenic role for these organisms in disease progression in addition to the previously characterized fusobacteria, proteobacteria, firmicutes, and bacteroidetes.
The peroxisome proliferator-activated receptor gamma (PPARG) gene encodes a transcription factor involved in the regulation of complex metabolic and inflammatory diseases. We investigated whether ...single nucleotide polymorphisms (SNPs) and haplotypes of the PPARG gene could contribute with susceptibility to develop periodontitis alone or together with type 2 diabetes mellitus (T2DM). Moreover, we evaluated the gene-phenotype association by assessing the subjects' biochemical and periodontal parameters, and the expression of PPARG and other immune response-related genes. We examined 345 subjects with a healthy periodontium and without T2DM, 349 subjects with moderate or severe periodontitis but without T2DM, and 202 subjects with moderate or severe periodontitis and T2DM. PPARG SNPs rs12495364, rs1801282, rs1373640, and rs1151999 were investigated. Multiple logistic regressions adjusted for age, sex, and smoking status showed that individuals carrying rs1151999-GG had a 64% lower chance of developing periodontitis together with T2DM. The CCGT haplotype increased the risk of developing periodontitis together with T2DM. The rs1151999-GG and rs12495364-TC were associated with reduced risk of obesity, periodontitis, elevated triglycerides, and elevated glycated hemoglobin, but there was no association with gene expression. Polymorphisms of the PPARG gene were associated with developing periodontitis together with T2DM, and with obesity, lipid, glycemic, and periodontal characteristics.
Aim
Investigate short‐term effects of power brushing following experimental induction of biofilm overgrowth in periodontal disease states.
Materials and Methods
Overall, 175 subjects representing ...each of five biofilm–gingival interface (BGI) periodontal groups were enrolled in a single‐blind, randomized study. After stent‐induced biofilm overgrowth for 21 days subjects received either a manual or a power toothbrush to use during a 4 weeks resolution phase. At baseline and during induction and resolution, standard clinical parameters were measured. Subclinical parameters included multikine analysis of 13 salivary biomarkers and 16s Human Oral Microbe Identification Microarray (HOMIM) probe analysis of subgingival plaque samples.
Results
All groups exhibited significantly greater reductions in bleeding on probing (BOP) (p = 0.002), gingival index (GI) (p = 0.0007), pocket depth (PD) (p = 0.04) and plaque index (p = 0.001) with power brushing compared to manual. When BGI groups were combined to form a shallow PD (PD ≤ 3 mm) and a deep PD group (PD > 4 mm) power brushing reduced BOP and GI in subjects with both pocket depths. Power brushing significantly reduced IL‐1β levels at resolution while changes in bacterial levels showed non‐significant trends between both brushing modalities.
Conclusions
Short‐term changes in select clinical parameters and subclinical salivary biomarkers may be useful in assessing efficacy of power brushing interventions in a spectrum of periodontal disease states.
Accumulating evidence suggests that bacteria associated with periodontal disease may exert systemic immunomodulatory effects. Although the improvement in oral hygiene practices in recent decades ...correlates with the increased incidence of asthma in developed nations, it is not known whether diseases of the respiratory system might be influenced by the presence of oral pathogens. The present study sought to determine whether subcutaneous infection with the anaerobic oral pathogen Porphyromonas gingivalis exerts a regulatory effect on allergic airway inflammation. BALB/c mice sensitized and subsequently challenged with ovalbumin exhibited airway hyperresponsiveness to methacholine aerosol and increased airway inflammatory cell influx and Th2 cytokine (interleukin-4 IL-4, IL-5, and IL-13) content relative to those in nonallergic controls. Airway inflammatory cell and cytokine contents were significantly reduced by establishment of a subcutaneous infection with P. gingivalis prior to allergen sensitization, whereas serum levels of ovalbumin-specific IgE and airway responsiveness were not altered. Conversely, subcutaneous infection initiated after allergen sensitization did not alter inflammatory end points but did reduce airway responsiveness in spite of increased serum IgE levels. These data provide the first direct evidence of a regulatory effect of an oral pathogen on allergic airway inflammation and responsiveness. Furthermore, a temporal importance of the establishment of infection relative to allergen sensitization is demonstrated for allergic outcomes.
Increasing evidence suggests that clinical signs of periodontal disease are independently associated with renal impairment. However, no studies have examined the possible linkage of kidney disease ...with serum antibody to oral pathogens.
The periodontal disease status was assessed in an older community-dwelling population (Dental Atherosclerosis Risk in Communities) to include: clinical measurements; oral biofilm microbial composition by DNA checkerboard, and serum antibody immunoglobulin-gamma (IgG) titers to specific bacteria by immunocheckerboard. Baseline characteristics were used to compute estimated glomerular filtration rate defining eGFR <60 ml/min/1.73 m(2) as impaired renal function in 103 of 5,032 subjects. Levels of serum IgG to specific oral bacteria were categorized by quartiles (comparing upper vs. lower three) as high titer and GFR <60 as the dependent variable in logistic regression models, adjusting for multiple comparisons (Hotelling T(2)) and traditional risk factors including age, race, smoking, diabetes, hypertension, body mass, waist-to-hip ratio, serum triglycerides, HDL, and LDL cholesterol.
High levels of serum IgG to selected periodontal pathogens including Porphyromonas gingivalis, Treponema denticola and Aggregobacter actinomycetemcomitans were associated with an increased odds for GFR <60 ml/min/1.73 m(2), adjusted odds ratio ranging from 1.6 to 1.8 and p < 0.05.
Elevated IgG to periodontal pathogens is significantly associated with impaired kidney function, independent of traditional risk factors. Prospective studies are necessary to confirm these findings.
Objectives We examined the potential association between prior chronic obstructive pulmonary disease (COPD) and edentulism, and whether the association varied by COPD severity using data from the ...Dental Atherosclerosis Risk in Communities Study. Design Cross-sectional. Setting Community dwelling subjects from four US communities. Participants and measurements Cases were identified as edentulous (without teeth) and subjects with one or more natural teeth were identified as dentate. COPD cases were defined by spirometry measurements that showed the ratio of forced expiratory volume (1 s) to vital capacity to be less than 0.7. The severity of COPD cases was also determined using a modified Global Initiative for Chronic Obstructive Lung Disease classification criteria (GOLD stage I–IV). Multiple logistic regression was used to examine the association between COPD and edentulism, while adjusting for age, gender, centre/race, ethnicity, education level, income, diabetes, hypertension, coronary heart disease and congestive heart failure, body mass index, smoking, smokeless tobacco use and alcohol consumption. Results 13 465 participants were included in this analysis (2087 edentulous; 11 378 dentate). Approximately 28.3% of edentulous participants had prior COPD compared with 19.6% among dentate participants (p<0.0001). After adjustment for potential confounders, we observed a 1.3 (1.08 to 1.62) and 2.5 (1.68 to 3.63) fold increased risk of edentulism among GOLD II and GOLD III/IV COPD, respectively, as compared with the non-COPD/dentate referent. Given the short period of time between the measurements of COPD (visit 2) and dentate status (visit 4) relative to the natural history of both diseases, neither temporality nor insight as to the directionality of the association can be ascertained. Conclusions We found a statistically significant association between prior COPD and edentulism, with evidence of a positive incremental effect seen with increasing GOLD classification.
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