sRNA23392 packaged by Porphyromonas gingivalis outer membrane vesicles promotes oral squamous cell carcinomas migration and invasion by targeting desmocollin‐2

2021 ◽  
Author(s):  
Dongjuan Liu ◽  
Sai Liu ◽  
Junchao Liu ◽  
Lei Miao ◽  
Shuwei Zhang ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Squamous Cell ◽  
Membrane Vesicles ◽  
Squamous Cell Carcinomas ◽  
Outer Membrane Vesicles ◽  
Migration And Invasion ◽  
Oral Squamous Cell Carcinomas

scholarly journals Melatonin Suppresses Oral Squamous Cell Carcinomas Migration and Invasion through Blocking FGF19/FGFR 4 Signaling Pathway

2021 ◽  
Vol 22 (18) ◽  
pp. 9907
Author(s):  
Leilei Wang ◽  
Yuxiong Su ◽  
Wing Shan Choi
Keyword(s):  
Squamous Cell ◽  
Squamous Cell Carcinomas ◽  
Migration And Invasion ◽  
Promising Alternative ◽  
Oral Squamous Cell Carcinomas ◽  
Invasion And Migration ◽  
Human Tongue ◽  
Underlying Mechanisms ◽  
And Migration ◽  
Fibroblast Growth Factor 19

Oral squamous cell carcinomas (OSCCs) are one of the most prevalent malignancies, with a low five-year survival rate, thus warranting more effective drugs or therapy to improve treatment outcomes. Melatonin has been demonstrated to exhibit oncostatic effects. In this study, we explored the anti-cancer effects of melatonin on OSCCs and the underlying mechanisms. A human tongue squamous cell carcinoma cell line (SCC-15) was treated with 2 mM melatonin, followed by transwell migration and invasion assays. Relative expression levels of Fibroblast Growth Factor 19 (FGF19) was identified by Cytokine Array and further verified by qPCR and Western blot. Overexpression and downregulation of FGF19 were obtained by adding exogenous hFGF19 and FGF19 shRNA lentivirus, respectively. Invasion and migration abilities of SCC-15 cells were suppressed by melatonin, in parallel with the decreased FGF19/FGFR4 expression level. Exogenous hFGF19 eliminated the inhibitory effects of melatonin on SCC-15 cells invasion and migration, while FGF19 knocking-down showed similar inhibitory activities with melatonin. This study proves that melatonin suppresses SCC-15 cells invasion and migration through blocking the FGF19/FGFR4 pathway, which enriches our knowledge on the anticancer effects of melatonin. Blocking the FGF19/FGFR4 pathway by melatonin could be a promising alternative for OSCCs prevention and management, which would facilitate further development of novel strategies to combat OSCCs.

scholarly journals Sphingolipid Containing Outer Membrane Vesicles Serve as a Delivery Vehicle to Limit Host Immune Response to Porphyromonas gingivalis

2020 ◽  
Author(s):  
Fernanda G. Rocha ◽  
Gregory Ottenberg ◽  
Zavier G. Eure ◽  
Mary E. Davey ◽  
Frank C. Gibson
Keyword(s):  
Immune Response ◽  
Inflammatory Response ◽  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Delivery Vehicle ◽  
Cellular Inflammatory Response ◽  
Elevated Expression ◽  
Host Inflammatory Response

ABSTRACTSphingolipids (SLs) are essential structural components of mammalian cell membranes. Our group recently determined that the oral anaerobe Porphyromonas gingivalis delivers its SLs to host cells, and that the ability of P. gingivalis to synthesize SLs limits the elicited host inflammatory response during cellular infection. As P. gingivalis robustly produces outer membrane vesicles (OMVs), we hypothesized that OMVs serve as a delivery vehicle for SLs, that the SL status of the OMVs may impact cargo loading to OMVs, and that SL-containing OMVs limit elicited host inflammation similar to that observed by direct bacterial challenge. Transwell cell culture experiments determined that in comparison to the parent strain W83, the SL-null mutant elicited a hyper-inflammatory immune response from THP-1 macrophage-like cells with elevated TNF-α, IL-1β, and IL-6. Targeted assessment of Toll-like receptors (TLRs) identified elevated expression of TLR2, unchanged TLR4, and elevated expression of the adaptor molecules MyD88 and TRIF by SL-null P. gingivalis. No significant differences in gingipain activity were observed in our infection models and both strains produced OMVs of similar size. Using comparative 2-dimensional gel electrophoresis we identified differences in the protein cargo of the OMVs between parent and SL-null strain. Importantly, use of purified OMVs recapitulated the cellular inflammatory response observed in the transwell system with whole bacteria. These findings provide new insights into the role of SLs in P. gingivalis OMV cargo assembly and expand our understanding of SL-OMVs as bacterial structures that modulate the host inflammatory response.

scholarly journals PPAD Activity Promotes Outer Membrane Vesicle Biogenesis and Surface Translocation by Porphyromonas gingivalis

2020 ◽  
Author(s):  
Danielle M. Vermilyea ◽  
M. Fata Moradali ◽  
Hey-Min Kim ◽  
Mary E. Davey
Keyword(s):  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Membrane Vesicle ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Virulence Determinants ◽  
Peptidylarginine Deiminase ◽  
Arginine Metabolism ◽  
Key Factor ◽  
Surface Translocation

Many bacteria switch between a sessile and a motile mode in response to environmental and host-related signals. Porphyromonas gingivalis, an oral anaerobe implicated in the etiology of chronic periodontal disease, has long been described as a non-motile bacterium. Yet, recent studies have shown that under certain conditions, P. gingivalis is capable of surface translocation. Considering these findings, this work aimed to increase our understanding as to how P. gingivalis transitions between sessile growth and surface migration. Here we show that the peptidylarginine deiminase secreted by P. gingivalis (PPAD), an enzyme previously shown to be upregulated during surface translocation and to constrain biofilm formation, promotes surface translocation. In the absence of PPAD, the production of outer membrane vesicles (OMVs) was drastically reduced. In turn, there was a reduction in gingipain-mediated proteolysis and a reduced zone of hydration around the site of inoculation. RNA-Seq and metabolomics analyses also showed that these changes corresponded to a shift in arginine metabolism. Overall, this study provides new evidence for the functional relevance of PPAD and proteases, as well as the importance of PPAD activity in OMV biogenesis and release. Our findings support the model that citrullination is a critical mechanism during lifestyle transition between surface-attached growth and surface translocation by modulating OMV-mediated proteolysis and arginine metabolism. IMPORTANCE Gram-negative bacteria produce nanosized OMVs that are actively released into their surroundings. The oral anaerobe P. gingivalis is prolific in OMV production and many of the proteins packaged in these vesicles are proteolytic or protein modifying enzymes. This includes key virulence determinants, such as the gingipains and PPAD (a unique peptidylarginine deiminase). Here, we show that PPAD activity (citrullination) is involved in OMV biogenesis. The study reveals an unusual mechanism that allows this bacterium to transform its surroundings. Since OMVs are detected in circulation and in systemic tissues, our study also supports the notion that PPAD activity may be a key factor in the correlation between periodontitis and systemic diseases further supporting PPAD as an important therapeutic target.

scholarly journals Citrullinome of Porphyromonas gingivalis Outer Membrane Vesicles: Confident Identification of Citrullinated Peptides

2019 ◽  
Vol 19 (1) ◽  
pp. 167-180 ◽  
Author(s):  
Daniel Nyberg Larsen ◽  
Christian Engelbrecht Mikkelsen ◽  
Mads Kierkegaard ◽  
Grzegorz P. Bereta ◽  
Zuzanna Nowakowska ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles

An Investigation into the Effects of Outer Membrane Vesicles and Lipopolysaccharide of Porphyromonas gingivalis on Blood-Brain Barrier Integrity, Permeability, and Disruption of Scaffolding Proteins in a Human in vitro Model

2022 ◽  
pp. 1-22
Author(s):  
Anna Barlach Pritchard ◽  
Zsolt Fabian ◽  
Clare L. Lawrence ◽  
Glyn Morton ◽  
StJohn Crean ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Human Brain ◽  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Virulence Factors ◽  
Membrane Vesicles ◽  
Outer Membrane Vesicles ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells

Background: The effects of the key pathogens and virulence factors associated with gum disease such as Porphyromonas gingivalis (P. gingivalis) on the central nervous system is of great interest with respect to development of neuropathologies and hence therapeutics and preventative strategies. Chronic infections and associated inflammation are known to weaken the first line of defense for the brain, the blood-brain barrier (BBB). Objective: The focus of this study is to utilize an established human in vitro BBB model to evaluate the effects of P. gingivalis virulence factors lipopolysaccharide (LPS) and outer membrane vesicles (OMVs) on a primary-derived human model representing the neurovascular unit of the BBB. Methods: Changes to the integrity of the BBB after application of P. gingivalis LPS and OMVs were investigated and correlated with transport of LPS. Additionally, the effect of P. gingivalis LPS and OMVs on human brain microvascular endothelial cells in monolayer was evaluated using immunofluorescence microscopy. Results: The integrity of the BBB model was weakened by application of P. gingivalis LPS and OMVs, as measured by a decrease in electrical resistance and a recovery deficit was seen in comparison to the controls. Application of P. gingivalis OMVs to a monoculture of human brain microvascular endothelial cells showed disruption of the tight junction zona occludens protein (ZO-1) compared to controls. Conclusion: These findings show that the integrity of tight junctions of the human BBB could be weakened by association with P. gingivalis virulence factors LPS and OMVs containing proteolytic enzymes (gingipains).

scholarly journals Outer Membrane Vesicles of Porphyromonas gingivalis Elicit a Mucosal Immune Response

PLoS ONE ◽  
2011 ◽  
Vol 6 (10) ◽  
pp. e26163 ◽  
Author(s):  
Ryoma Nakao ◽  
Hideki Hasegawa ◽  
Kuniyasu Ochiai ◽  
Shogo Takashiba ◽  
Akira Ainai ◽  
...  
Keyword(s):  
Immune Response ◽  
Outer Membrane ◽  
Porphyromonas Gingivalis ◽  
Membrane Vesicles ◽  
Mucosal Immune Response ◽  
Outer Membrane Vesicles
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