ArticleMolecular medicine (Cambridge, Mass.)2014
The α7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function.
Article in Molecular medicine (Cambridge, Mass.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 26 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 49 citations in OpenAlex.
- Impact of Neuroimmune System Activation by Adolescent Binge Alcohol Exposure on Adult Neurobiology.Advances in experimental medicine and biology · 2025Review
- Therapeutic implications of SARS-CoV-2 dysregulation of the gut-brain-lung axis.World journal of gastroenterology · 2021Review
- Nicotinic α7 acetylcholine receptor (α7nAChR) in human airway smooth muscle.Archives of biochemistry and biophysics · 2021Article
- Vagus nerve stimulation enhances the cholinergic anti-inflammatory pathway to reduce lung injury in acute respiratory distress syndrome via STAT3.Cell death discovery · 2021Article
- Review
- Loss of Basal Forebrain Cholinergic Neurons Following Adolescent Binge Ethanol Exposure: Recovery With the Cholinesterase Inhibitor Galantamine.Frontiers in behavioral neuroscience · 2021Article
- Retraction Note: The α7 nicotinic acetylcholine receptor agonist GTS-21 improves bacterial clearance in mice by restoring hyperoxia-compromised macrophage function.Molecular medicine (Cambridge, Mass.) · 2020Article
- The α7 nicotinic acetylcholine receptor agonist, GTS-21, attenuates hyperoxia-induced acute inflammatory lung injury by alleviating the accumulation of HMGB1 in the airways and the circulation.Molecular medicine (Cambridge, Mass.) · 2020Article
- The cholinergic anti-inflammatory pathway alleviates acute lung injury.Molecular medicine (Cambridge, Mass.) · 2020Article
- Vagal-α7nAChR signaling promotes lung stem cells regeneration via fibroblast growth factor 10 during lung injury repair.Stem cell research & therapy · 2020Article
- The nitric oxide donor, (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NONOate/D-NO), increases survival by attenuating hyperoxia-compromised innate immunity in bacterial clearance in a mouse model of ventilator-associated pneumonia.Biochemical pharmacology · 2020Article
- Dietary Antioxidants Significantly Attenuate Hyperoxia-Induced Acute Inflammatory Lung Injury by Enhancing Macrophage Function via Reducing the Accumulation of Airway HMGB1.International journal of molecular sciences · 2020Article
- The Role of HMGB1, a Nuclear Damage-Associated Molecular Pattern Molecule, in the Pathogenesis of Lung Diseases.Antioxidants & redox signaling · 2019Review
- Distinct Roles of α7 nAChRs in Antigen-Presenting Cells and CD4Frontiers in immunology · 2019Article
- The Cholinergic Anti-Inflammatory Response and the Role of Macrophages in HIV-Induced Inflammation.International journal of molecular sciences · 2018Review
- Activation of Central Alpha 7 Nicotinic Acetylcholine Receptor Reverses Suppressed Immune Function of T Lymphocytes and Protects Against Sepsis Lethality.International journal of biological sciences · 2018Article
- Emerging role of HMGB1 in lung diseases: friend or foe.Journal of cellular and molecular medicine · 2017Review
- Original Research: Evaluation of pulmonary response to inhaled tungsten (IV) oxide nanoparticles in golden Syrian hamsters.Experimental biology and medicine (Maywood, N.J.) · 2017Article
- Signals of vagal circuits engaging with AKT1 in α7 nAChRCell discovery · 2017Article
- The Protective Effect of Alpha 7 Nicotinic Acetylcholine Receptor Activation on Critical Illness and Its Mechanism.International journal of biological sciences · 2017Review
Corrections and comments
- Retraction · 2020-12-30Falsification/Fabrication of Data · Falsification/Fabrication of Image · Investigation by Company/Institution · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author · Upgrade/Update of Prior Notice(s) · · Daniel J Antoine has institutional finding of misconduct; see also: https://news.liverpool.ac.uk/2020/08/17/further-update-on-research-misconduct-investigation/;
- Expression of concern · 2020-02-03Concerns/Issues about Results and/or Conclusions · Investigation by Company/Institution · Updated to Retraction ·
- Expression of concern
- Retracted
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mechanical ventilation with supraphysiological concentrations of oxygen (hyperoxia) is routinely used to treat patients with respiratory distress. However, prolonged exposure to hyperoxia compromises the ability of the macrophage to phagocytose and clear bacteria. Previously, we showed that the exposure of mice to hyperoxia elicits the release of the nuclear protein high mobility group box-1 (HMGB1) into the airways. Extracellular HMGB1 impairs macrophage phagocytosis and increases the mortality of mice infected with Pseudomonas aeruginosa (PA). The aim of this study was to determine whether GTS-21 [3-(2,4 dimethoxybenzylidene)-anabaseine dihydrochloride], an α7 nicotinic acetylcholine receptor (α7nAChR) agonist, could inhibit hyperoxia-induced HMGB1 release into the airways, enhance macrophage function and improve bacterial clearance from the lungs in a mouse model of ventilator-associated pneumonia. GTS-21 (0.04, 0.4 and 4 mg/kg) or saline was systemically administered via intraperitoneal injection to mice that were exposed to hyperoxia (≥99% O2) and subsequently challenged with PA. We found that systemic administration of 4 mg/kg GTS-21 significantly increased bacterial clearance, decreased acute lung injury and decreased accumulation of airway HMGB1. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophagelike cell line, were incubated with different concentrations of GTS-21 in the presence of 95% O2. The phagocytic activity of macrophages was significantly increased by GTS-21 in a dose-dependent manner. In addition, hyperoxia-induced hyperacetylation of HMGB1 was significantly reduced in macrophages incubated with GTS-21. Furthermore, GTS-21 significantly inhibited the cytoplasmic translocation and release of HMGB1 from these macrophages. Our results indicate that GTS-21 is effective in improving bacterial clearance and reducing acute lung injury by enhancing macrophage function via inhibiting the release of nuclear HMGB1. Therefore, the α7nAChR represents a possible pharmacological target to improve the clinical outcome of patients on ventilators by augmenting host defense against bacterial infections.
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