Phosphatidylinositol 3-Kinase/Akt signal pathway resists the apoptosis and inflammation in human extravillous trophoblasts induced by Porphyromonas gingivalis

2018 ◽  
Vol 104 ◽  
pp. 100-107 ◽  
Author(s):  
Haiying Guo ◽  
Hongyu Ren ◽  
Shanshan Liang ◽  
Yaoting Ji ◽  
Han Jiang ◽  
...  
Keyword(s):  
Porphyromonas Gingivalis ◽  
Signal Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Apoptosis And Inflammation ◽  
Extravillous Trophoblasts ◽  
Phosphatidylinositol 3

scholarly journals Silencing of SPP1 Suppresses Progression of Tongue Cancer by Mediating the PI3K/Akt Signaling Pathway

2020 ◽  
Vol 19 ◽  
pp. 153303382097130
Author(s):  
Qiaoli Zhang ◽  
Lifeng Li ◽  
Yueli Lai ◽  
Tong Zhao
Keyword(s):  
Protein Interaction ◽  
Protein Interaction Network ◽  
Tongue Cancer ◽  
Interaction Network ◽  
Signal Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Protein Protein Interaction ◽  
Si Rna ◽  
Protein Protein Interaction Network ◽  
Phosphatidylinositol 3

Background: In the present study, we aimed to find an effective target for the treatment of tongue cancer using gene chip screening and signal pathway research. Methods: We used microarray screening and gene expression profile analyses to find important differentially expressed genes in tongue cancer. We constructed a protein-protein interaction network, and used enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes to screen for important genes. We then silenced the genes of interest in SCC154 cells to study the relationship with the Phosphatidylinositol 3-kinase/Akt signal pathway. Western blot analyses, the 3-(4,5Dimethylthiazol-yl)-2,5Dimethylthiazol-2-yl)-2,5diphenyltetrazolium bromide (MTT) test, and immunofluorescence assays were used to compare the expression levels of Phosphatidylinositol 3-kinase/Akt signal pathway-related proteins, cell viability, and cell proliferation ability in normal SCC154 cells, Si-RNA SCC154 cells, and gene-silenced SCC154 cells. The scratch test, Transwell test, and western blotting were used to determine migration, invasion, and carcinogenesis. Results: Using GSE9844, GSE13601, and GSE31056 gene chips, we identified 93 upregulated genes and 76 downregulated genes in tongue cancer. Using the protein-protein interaction network and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we further identified 47 differentially expressed genes. Using Kaplan-Meier plotter online tools, we also identified 3 genes (SPP1, Recombinant Human Secreted Phosphoprotein 1; PLAU, plasminogen activator urinary; and APP, amyloid precursor protein). Compared with normal SCC154 cells and Si-RNA control SCC154 cells, the expressions of Phosphatidylinositol 3-kinase/Akt pathway proteins in si-SPP1 SCC154 cells were significantly decreased (*P < 0.05), and the protein activities and proliferation abilities were also significantly decreased (*P < 0.05), while the migration ability, invasion ability, and cancer forming ability were significantly increased (*P < 0.05). Conclusion: Inhibition of the SPP1 gene may have a therapeutic effect on tongue cancer, and could be an effective target for the treatment of this disorder.

scholarly journals Porphyromonas gingivalis Fimbriae Proactively Modulate β2 Integrin Adhesive Activity and Promote Binding to and Internalization by Macrophages

2006 ◽  
Vol 74 (10) ◽  
pp. 5658-5666 ◽  
Author(s):  
George Hajishengallis ◽  
Min Wang ◽  
Evlambia Harokopakis ◽  
Martha Triantafilou ◽  
Kathy Triantafilou
Keyword(s):  
Porphyromonas Gingivalis ◽  
Chinese Hamster Ovary Cells ◽  
Chinese Hamster ◽  
Binding Activity ◽  
Kinase Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
High Affinity ◽  
Inside Out ◽  
Tlr2 Signaling ◽  
Phosphatidylinositol 3

ABSTRACT In monocytes, the fimbriae of the oral pathogen Porphyromonas gingivalis activate cross talk signaling from Toll-like receptor 2 (TLR2) to the β2 integrin CD11b/CD18, leading to the induction of the high-affinity state of the latter receptor. CD14 plays an important role in this “inside-out” proadhesive pathway by binding fimbriae and facilitating the activation of TLR2 and phosphatidylinositol 3-kinase signaling. In its high-affinity state, CD11b/CD18 mediates monocyte adhesion to endothelial cells and transmigration to sites of infection. We have now shown that P. gingivalis fimbriae function as both an activator and a ligand of CD11b/CD18; thus, fimbriae proactively promote their own binding to monocytes. Indeed, treatments that interfered with fimbria-induced activation of CD11b/CD18 (i.e., blockade of CD14, TLR2, or phosphatidylinositol 3-kinase signaling) also suppressed the cell binding activity of fimbriae, which was largely inducible and CD11b/CD18 dependent. Development of a recombinant inside-out signaling system in Chinese hamster ovary cells confirmed the ability of fimbriae to activate CD14/TLR2 signaling and induce their own CD11b/CD18-dependent binding. Induction of this proadhesive pathway by P. gingivalis fimbriae appeared to take place in lipid rafts. Indeed, methyl-β-cyclodextrin, a cholesterol-sequestering agent that disrupts lipid raft organization, was found to inhibit the fimbria-induced assembly of CD14/TLR2 signaling complexes and the activation of the high-affinity state of CD11b/CD18. Experiments using macrophages from mice deficient in various pattern recognition receptors indicated that the receptors involved in the inside-out proadhesive pathway (CD14, TLR2, and CD11b/CD18) are important for mediating P. gingivalis internalization within macrophages. It therefore appears that P. gingivalis proactively modulates β2 integrin adhesive activity for intracellular uptake.

scholarly journals Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Contributes to Survival of Primary Epithelial Cells Infected with the Periodontal Pathogen Porphyromonas gingivalis

2004 ◽  
Vol 72 (7) ◽  
pp. 3743-3751 ◽  
Author(s):  
Özlem Yilmaz ◽  
Thomas Jungas ◽  
Philippe Verbeke ◽  
David M. Ojcius
Keyword(s):  
Epithelial Cells ◽  
Host Cell ◽  
Porphyromonas Gingivalis ◽  
Periodontal Pathogen ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitor Ly294002 ◽  
Mitochondrial Membrane Depolarization ◽  
Infected Cells ◽  
Phosphatidylinositol 3

ABSTRACT Porphyromonas gingivalis, an important periodontal pathogen, infects primary gingival epithelial cells (GECs). Despite the large number of bacteria that replicate inside the GECs, the host cell remains viable. We demonstrate that P. gingivalis triggers rapid and reversible surface phosphatidylserine exposure through a mechanism requiring caspase activation. However, after 1 day of infection, the bacteria no longer induce phosphatidylserine externalization and instead protect infected cells against apoptosis. Infection exerts its effect at the level of mitochondria, as P. gingivalis also blocks depolarization of the mitochondrial transmembrane potential and cytochrome c release. Interestingly, protein kinase B/Akt is phosphorylated during infection, which can be blocked with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Suppression of the PI3K/Akt pathway following staurosporine treatment results in mitochondrial-membrane depolarization, cytochrome c release, DNA fragmentation, and increased apoptosis of infected GECs. Thus, P. gingivalis stimulates early surface exposure of phosphatidylserine, which could downmodulate the inflammatory response, while also promoting host cell survival through the PI3K/Akt pathway.

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