ArticleCellular microbiology2014
Blockade of the PI-3K signalling pathway by the Aggregatibacter actinomycetemcomitans cytolethal distending toxin induces macrophages to synthesize and secrete pro-inflammatory cytokines.
Article in Cellular microbiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
40 citing papers in PubMed, 55 citations in OpenAlex.
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- Current Knowledge about Gastric Microbiota with Special Emphasis onCurrent issues in molecular biology · 2024Review
- Campylobacter jejuni virulence factors: update on emerging issues and trends.Journal of biomedical science · 2024Review
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- Cellugyrin (synaptogyrin-2) dependent pathways are used by bacterial cytolethal distending toxin and SARS-CoV-2 virus to gain cell entry.Frontiers in cellular and infection microbiology · 2024Article
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- Chronic exposure to Cytolethal Distending Toxin (CDT) promotes a cGAS-dependent type I interferon response.Cellular and molecular life sciences : CMLS · 2021Article
- Cytolethal distending toxin: from genotoxin to a potential biomarker and anti-tumor target.World journal of microbiology & biotechnology · 2021Review
- Assessment of a Small Molecule Synthetic Lignan in Enhancing Oxidative Balance and Decreasing Lipid Accumulation in Human Retinal Pigment Epithelia.International journal of molecular sciences · 2021Article
- The Active Subunit of the Cytolethal Distending Toxin, CdtB, Derived From BothFrontiers in cellular and infection microbiology · 2021Article
- Rab5a Promotes Cytolethal Distending Toxin B-Induced Cytotoxicity and Inflammation.Infection and immunity · 2020Article
- Gut Microbiota and Colon Cancer: A Role for Bacterial Protein Toxins?International journal of molecular sciences · 2020Review
- Cytolethal distending toxin-induced release of interleukin-1β by human macrophages is dependent upon activation of glycogen synthase kinase 3β, spleen tyrosine kinase (Syk) and the noncanonical inflammasome.Cellular microbiology · 2020Article
- Bacterial Genotoxin-Induced DNA Damage and Modulation of the Host Immune Microenvironment.Toxins · 2020Review
- The Cell-Cycle Regulatory Protein p21Pathogens (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The Aggregatibactor actinomycetemcomitans cytolethal distending toxin (Cdt) induces G2 arrest and apoptosis in lymphocytes; these toxic effects are due to the active subunit, CdtB, which functions as a phosphatidylinositol-3,4,5-triphosphate (PIP3) phosphatase. We now extend our investigation and demonstrate that Cdt is able to perturb human macrophage function. THP-1- and monocyte-derived macrophages were found not to be susceptible to Cdt-induced apoptosis. Nonetheless, the toxin was capable of binding to macrophages and perturbing PI-3K signalling resulting in decreased PIP3 levels and reduced phosphorylation of Akt and GSK3β; these changes were accompanied by concomitant alterations in kinase activity. Exposure of monocytes and macrophages to Cdt resulted in pro-inflammatory cytokine production including increased expression and release of IL-1β, TNFα and IL-6. Furthermore, treatment of cells with either TLR-2, -3 or -4 agonists in the presence of Cdt resulted in an augmented pro-inflammatory response relative to agonist alone. GSK3β inhibitors blocked the Cdt-induced pro-inflammatory cytokine response suggesting a pivotal role for PI-3K blockade, concomitant decrease in GSK3β phosphorylation and increased kinase activity. Collectively, these studies provide new insight into the virulence potential of Cdt in mediating the pathogenesis of disease caused by Cdt-producing organisms.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.