scholarly journals Effects of a tart cherry (Prunus cerasus L.) phenolic extract on Porphyromonas gingivalis and its ability to impair the oral epithelial barrier

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246194
Author(s):  
Amel Ben Lagha ◽  
Geneviève Pellerin ◽  
Katy Vaillancourt ◽  
Daniel Grenier

Periodontal diseases, including gingivitis and periodontitis, are a global oral health problem. Porphyromonas gingivalis, a key pathogen involved in the onset of periodontitis, is able to colonize the subgingival epithelium and invade the underlying connective tissue due to the contribution of cysteine proteases known as gingipains. In this study, we investigated the effects of a phenolic extract prepared from tart cherry (Prunus cerasus L.) juice on the growth, adherence, and protease activity of P. gingivalis. We also assessed the protective effect of the tart cherry extract on the disruption of the oral epithelial barrier induced by P. gingivalis. The tart cherry extract that contains procyanidins and quercetin and its derivatives (rutinoside, glucoside) as the most important phenolic compounds attenuated P. gingivalis growth, reduced adherence to an experimental basement membrane matrix model, and decreased the protease activities of P. gingivalis. The tart cherry extract also exerted a protective effect on the integrity of the oral epithelial barrier in an in vitro model infected with P. gingivalis. More specifically, the extract prevented a decrease in transepithelial electrical resistance as well as the destruction of tight junction proteins (zonula occludens-1 and occludin). These results suggest that the tart cherry phenolic extract may be a promising natural product for the treatment of periodontitis through its ability to attenuate the virulence properties of P. gingivalis and curtail the ability of this pathogen to impair the oral epithelial barrier.

2001 ◽  
Vol 12 (3) ◽  
pp. 192-216 ◽  
Author(s):  
M.A. Curtis ◽  
J. Aduse-Opoku ◽  
M. Rangarajan

The cysteine proteases of Porphyromonas gingivalis are extracellular products of an important etiological agent in periodontal diseases. Many of the in vitro actions of these enzymes are consistent with the observed deregulated inflammatory and immune features of the disease. They are significant targets of the immune responses of affected individuals and are viewed by some as potential molecular targets for therapeutic approaches to these diseases. Furthermore, they appear to represent a complex group of genes and protein products whose transcriptional and translational control and maturation pathways may have a broader relevance to virulence determinants of other persistent bacterial pathogens of human mucosal surfaces. As a result, the genetics, chemistry, and virulence-related properties of the cysteine proteases of P. gingivalis have been the focus of much research effort over the last ten years. In this review, we describe some of the progress in their molecular characterization and how their putative biological roles, in relation to the in vivo growth and survival strategies of P. gingivalis, may also contribute to the periodontal disease process.


2001 ◽  
Vol 69 (7) ◽  
pp. 4242-4247 ◽  
Author(s):  
K. Nisapakultorn ◽  
K. F. Ross ◽  
M. C. Herzberg

ABSTRACT Calprotectin, an S100 calcium-binding protein with broad-spectrum antimicrobial activity in vitro, is expressed in neutrophils, monocytes, and gingival keratinocytes. In periodontitis, calprotectin appears upregulated and is detected at higher levels in gingival crevicular fluid and tissue specimens. How calprotectin contributes to the pathogenesis of periodontal diseases is unknown. To isolate the effects of calprotectin, a calprotectin-negative oral epithelial cell line was transfected with calprotectin genes to enable expression.Porphyromonas gingivalis was permitted to bind and invade transfected cells expressing calprotectin and sham transfectants. Rates of invasion into both cell lines were compared using the antibiotic protection assay. Transfected cells expressing calprotectin showed 40 to 50% fewer internalized P. gingivalis than sham transfectants. Similarly, binding to calprotectin expressing cells was reduced approximately twofold at all time points (15, 30, 45, and 60 min) as estimated by immunofluorescence analysis. Independent of invasion, however, prolonged exposure to P. gingivalisinduced epithelial cell rounding and detachment from the substratum. These morphological changes were delayed, however, in cells expressing calprotectin. Using P. gingivalis protease-deficient mutants, we found that Arg-gingipain and Lys-gingipain contributed to epithelial cell rounding and detachment. In conclusion, expression of calprotectin appears to protect epithelial cells in culture against binding and invasion by P. gingivalis. In addition, cells expressing calprotectin are more resistant to detachment mediated by Arg-gingipain and Lys-gingipain. In periodontal disease, calprotectin may augment both the barrier protection and innate immune functions of the gingival epithelium to promote resistance to P. gingivalis infection.


2019 ◽  
Vol 98 (10) ◽  
pp. 1150-1158 ◽  
Author(s):  
W. Chen ◽  
A. Alshaikh ◽  
S. Kim ◽  
J. Kim ◽  
C. Chun ◽  
...  

Oral mucosa provides the first line of defense against a diverse array of environmental and microbial irritants by forming the barrier of epithelial cells interconnected by multiprotein tight junctions (TJ), adherens junctions, desmosomes, and gap junction complexes. Grainyhead-like 2 (GRHL2), an epithelial-specific transcription factor, may play a role in the formation of the mucosal epithelial barrier, as it regulates the expression of the junction proteins. The current study investigated the role of GRHL2 in the Porphyromonas gingivalis ( Pg)–induced impairment of epithelial barrier functions. Exposure of human oral keratinocytes (HOK-16B and OKF6 cells) to Pg or Pg-derived lipopolysaccharides ( Pg LPSs) led to rapid loss of endogenous GRHL2 and the junction proteins (e.g., zonula occludens, E-cadherin, claudins, and occludin). GRHL2 directly regulated the expression levels of the junction proteins and the epithelial permeability for small molecules (e.g., dextrans and Pg bacteria). To explore the functional role of GRHL2 in oral mucosal barrier, we used a Grhl2 conditional knockout (KO) mouse model, which allows for epithelial tissue-specific Grhl2 KO in an inducible manner. Grhl2 KO impaired the expression of the junction proteins at the junctional epithelium and increased the alveolar bone loss in the ligature-induced periodontitis model. Fluorescence in situ hybridization revealed increased epithelial penetration of oral bacteria in Grhl2 KO mice compared with the wild-type mice. Also, blood loadings of oral bacteria (e.g., Bacteroides, Bacillus, Firmicutes, β- proteobacteria, and Spirochetes) were significantly elevated in Grhl2 KO mice compared to the wild-type littermates. These data indicate that Pg bacteria may enhance paracellular penetration through oral mucosa in part by targeting the expression of GRHL2 in the oral epithelial cells, which then impairs the epithelial barrier by inhibition of junction protein expression, resulting in increased alveolar tissue destruction and systemic bacteremia.


2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Isaac Maximiliano Bugueno ◽  
Fareeha Batool ◽  
Laetitia Keller ◽  
Sabine Kuchler-Bopp ◽  
Nadia Benkirane-Jessel ◽  
...  

2009 ◽  
Vol 53 (8) ◽  
pp. 3308-3316 ◽  
Author(s):  
Hiroyuki Wakabayashi ◽  
Koji Yamauchi ◽  
Tetsuo Kobayashi ◽  
Tomoko Yaeshima ◽  
Keiji Iwatsuki ◽  
...  

ABSTRACT Lactoferrin (LF) is an iron-binding antimicrobial protein present in saliva and gingival crevicular fluids, and it is possibly associated with host defense against oral pathogens, including periodontopathic bacteria. In the present study, we evaluated the in vitro effects of LF-related agents on the growth and biofilm formation of two periodontopathic bacteria, Porphyromonas gingivalis and Prevotella intermedia, which reside as biofilms in the subgingival plaque. The planktonic growth of P. gingivalis and P. intermedia was suppressed for up to 5 h by incubation with ≥130 μg/ml of human LF (hLF), iron-free and iron-saturated bovine LF (apo-bLF and holo-bLF, respectively), and ≥6 μg/ml of bLF-derived antimicrobial peptide lactoferricin B (LFcin B); but those effects were weak after 8 h. The biofilm formation of P. gingivalis and P. intermedia over 24 h was effectively inhibited by lower concentrations (≥8 μg/ml) of various iron-bound forms (the apo, native, and holo forms) of bLF and hLF but not LFcin B. A preformed biofilm of P. gingivalis and P. intermedia was also reduced by incubation with various iron-bound bLFs, hLF, and LFcin B for 5 h. In an examination of the effectiveness of native bLF when it was used in combination with four antibiotics, it was found that treatment with ciprofloxacin, clarithromycin, and minocycline in combination with native bLF for 24 h reduced the amount of a preformed biofilm of P. gingivalis compared with the level of reduction achieved with each agent alone. These results demonstrate the antibiofilm activity of LF with lower iron dependency against P. gingivalis and P. intermedia and the potential usefulness of LF for the prevention and treatment of periodontal diseases and as adjunct therapy for periodontal diseases.


Author(s):  
Mohsen Ali Al-Hamzi ◽  
Ayman Ahmed Ahmed Al-jorany ◽  
Hassan A. Al-Shamahy ◽  
Amani Abdulhakeem Al-Sharani

Chronic periodentitis is a quite common disease in adult patients characterized by pocket formation and/or recession while progressive loss of periodontal attachment occurs slowly to moderately local risk factors, e.g. bacterial plaque. Wide array of microorganisms have been associated with periodontal disease, out of which Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg) have been predominantly associated with periodontal diseases. The objectives of this study were to determine phototoxic effect of visible blue light on Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis clinical isolates from chronic periodentitis patients, and to study their antibiotic sensitivity against selected antibiotics. The test was carried out on 15 strains of Aggregatibacter actinomycetemcomitans and 15 strains of Porphyromonas gingivalis isolated from pockets of chronic periodentitis patients aged between 30-50 years old with pocket depths of 5-6 mm. The bacteria cultured, isolated, and identified by standard bacteriological methods, then subjected to visible blue light at different periods of time exposures. After light exposure, the bacterial killing rates were calculated from colony forming unit (CFU) counts after 48hours of anaerobic incubation. There was a decrease in CFU for both microorganisms as we proceeded from zero, 20, 40 and 60 seconds of blue light exposure. In conclusions, there was a phototoxic effect for the visible blue light emitted from the light curing device against the anaerobic periodontal pathogens and blue light exposure is effective in reducing periodontal pathogens. It is recommended that an adjunctive exogenous photosensitizer be used and that pathogens be exposed to visible light for clinical antimicrobial periodontal therapy.


1996 ◽  
Vol 64 (2) ◽  
pp. 660-664 ◽  
Author(s):  
P N Madianos ◽  
P N Papapanou ◽  
U Nannmark ◽  
G Dahlén ◽  
J Sandros

2008 ◽  
Vol 57 (4) ◽  
pp. 500-507 ◽  
Author(s):  
Akiko Uehara ◽  
Mariko Naito ◽  
Takahisa Imamura ◽  
Jan Potempa ◽  
James Travis ◽  
...  

Cysteine proteinases from Porphyromonas gingivalis, or gingipains, are considered to be key virulence factors of the bacterium in relation to periodontal diseases. Incubation of human oral epithelial cells with lysine-specific gingipain (Kgp) and high-molecular-mass arginine-specific gingipain (HRgpA) resulted in a decrease in the production of interleukin (IL)-8, but not in the production of other pro-inflammatory cytokines. In contrast, arginine-specific gingipain 2 (RgpB) increased IL-8 production. RNA interference assays demonstrated that Kgp- and HRgpA-mediated downregulation and RgpB-mediated upregulation occurred through protease-activated receptor (PAR)-1 and PAR-2 signalling. Although the RgpB-mediated upregulation of IL-8 production occurred through nuclear factor-kappa B (NF-κB), the Kgp- and HRgpA-mediated downregulation was not negated in NF-κB-silenced cells. Both the haemagglutinin and the enzymic domains are required for Kgp and HRgpA to downregulate the production of IL-8 in human oral epithelial cells, and the two domains are thought to co-exist. These results suggest that gingipains preferentially suppress IL-8, resulting in attenuation of the cellular recognition of bacteria, and as a consequence, sustain chronic inflammation.


Sign in / Sign up

Export Citation Format

Share Document