ArticleMolecular medicine (Cambridge, Mass.)2012
Inhibition of high-mobility group box 1 protein (HMGB1) enhances bacterial clearance and protects against Pseudomonas Aeruginosa pneumonia in cystic fibrosis.
Article in Molecular medicine (Cambridge, Mass.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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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.
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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
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- The Effect of Conservative Oxygen Therapy in Reducing Mortality in Critical Care Patients: A Meta-Analysis and Trial Sequential Analysis.Frontiers in medicine · 2021Pooled it
- Are Sputum High Mobility Group Box 1 and D-Dimer Changes Relevant Markers of Tissue Damage and Fibrinolysis in Cystic Fibrosis?Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Article
- Necroptosis induced by MLKL overexpression in liver triggers cellular senescence and leads to chronic inflammation and fibrosis.GeroScience · 2026Article
- Myeloid cell-specific HMGB1 deficiency exaggerates mucoinflammatory responses but promotes bacterial clearance in mucoinflammatory lung disease.Scientific reports · 2026Article
- HMGB1 and metabolic pathways in Acinetobacter baumannii pneumonia: an associative study.BMC infectious diseases · 2025Article
- Radiation-induced eCIRP impairs macrophage bacterial phagocytosis.Journal of leukocyte biology · 2024Article
- Review
- AMPK activation improves recovery from pneumonia-induced lung injury via reduction of er-stress and apoptosis in alveolar epithelial cells.Respiratory research · 2023Article
- Article
- Dioleoylphosphatidylglycerol Inhibits Heat Shock Protein B4 (HSPB4)-Induced Inflammatory Pathways In Vitro.International journal of molecular sciences · 2023Article
- The chemokine landscape: one system multiple shades.Frontiers in immunology · 2023Review
- Pamoic acid is an inhibitor of HMGB1·CXCL12 elicited chemotaxis and reduces inflammation in murine models of Pseudomonas aeruginosa pneumonia.Molecular medicine (Cambridge, Mass.) · 2022Article
- Dual effects of supplemental oxygen on pulmonary infection, inflammatory lung injury, and neuromodulation in aging and COVID-19.Free radical biology & medicine · 2022Review
- RNase 7 Inhibits UropathogenicInternational journal of molecular sciences · 2022Article
- From Inflammation to Fibrosis: Novel Insights into the Roles of High Mobility Group Protein Box 1 in Schistosome-Induced Liver Damage.Pathogens (Basel, Switzerland) · 2022Review
- Too much tolerance for hyperoxemia in mechanically ventilated patients with SARS-CoV-2 pneumonia? Report from an Italian intensive care unit.Frontiers in medicine · 2022Article
- Airway epithelial cell-specific deletion of HMGB1 exaggerates inflammatory responses in mice with muco-obstructive airway disease.Frontiers in immunology · 2022Article
- Targeting Inflammation Driven by HMGB1 in Bacterial Keratitis-A Review.Pathogens (Basel, Switzerland) · 2021Review
- Bioenergetic maladaptation and release of HMGB1 in calcineurin inhibitor-mediated nephrotoxicity.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- 2-O, 3-O desulfated heparin (ODSH) increases bacterial clearance and attenuates lung injury in cystic fibrosis by restoring HMGB1-compromised macrophage function.Molecular medicine (Cambridge, Mass.) · 2021Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Pulmonary infection with Pseudomonas aeruginosa and neutrophilic lung inflammation significantly contribute to morbidity and mortality in cystic fibrosis (CF). High-mobility group box 1 protein (HMGB1), a ubiquitous DNA binding protein that promotes inflammatory tissue injury, is significantly elevated in CF sputum. However, its mechanistic and potential therapeutic implications in CF were previously unknown. We found that HMGB1 levels were significantly elevated in bronchoalveolar lavage fluids (BALs) of CF patients and cystic fibrosis transmembrane conductance regulator (CFTR )(-/-) mice. Neutralizing anti-HMGB1 monoclonal antibody (mAb) conferred significant protection against P. aeruginosa-induced neutrophil recruitment, lung injury and bacterial infection in both CFTR(-/-) and wild-type mice. Alveolar macrophages isolated from mice treated with anti-HMGB1 mAb had improved phagocytic activity, which was suppressed by direct exposure to HMGB1. In addition, BAL from CF patients significantly impaired macrophage phagocytotic function, and this impairment was attenuated by HMGB1-neutralizing antibodies. The HMGB1-mediated suppression of bacterial phagocytosis was attenuated in macrophages lacking toll-like receptor (TLR)-4, suggesting a critical role for TLR4 in signaling HMGB1-mediated macrophage dysfunction. These studies demonstrate that the elevated levels of HMGB1 in CF airways are critical for neutrophil recruitment and persistent presence of P. aeruginosa in the lung. Thus, HMGB1 may provide a therapeutic target for reducing bacterial infection and lung inflammation in CF.
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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.