ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02595060 (GM-CSF Inhalation to Improve Host Defense and Pulmonary Barrier Restoration), which is not on this map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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.
GM-CSF Inhalation to Improve Host Defense and Pulmonary Barrier Restoration (GI-HOPE). A Randomized, Double-blind, Parallel Group, Multicenter, Phase II Study
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- Association between TLR4 A299G polymorphism and pneumonia risk: a meta-analysis.Medical science monitor : international medical journal of experimental and clinical research · 2015Pooled it
- Phage therapy for Klebsiella pneumoniae: Understanding bacteria-phage interactions for therapeutic innovations.PLoS pathogens · 2025Review
- Insights into the roles of macrophages in Klebsiella pneumoniae infections: a comprehensive review.Cellular & molecular biology letters · 2025Review
- Bilobalide attenuates lipopolysaccharide‑induced HepG2 cell injury by inhibiting TLR4‑NF‑κB signaling via the PI3K/Akt pathway.Experimental and therapeutic medicine · 2024Article
- Cell-free hemoglobin triggers macrophage cytokine production via TLR4 and MyD88.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Autophagy, cell death, and cytokines inEmerging microbes & infections · 2023Review
- Alveolar macrophages in tissue homeostasis, inflammation, and infection: evolving concepts of therapeutic targeting.The Journal of clinical investigation · 2023Review
- In vivo single-cell transcriptomics reveal Klebsiella pneumoniae skews lung macrophages to promote infection.EMBO molecular medicine · 2022Article
- Review
- Host Immune Response to Clinical HypervirulentJournal of immunology research · 2022Article
- miR-140-5p Overexpression Protects Against Lipopolysaccharide-Induced Necrotizing PneumoniaCellular and molecular bioengineering · 2021Article
- Tenascin-C Deficiency Is Associated With Reduced Bacterial Outgrowth DuringFrontiers in immunology · 2021Article
- The Role of Innate Immunity in Pulmonary Infections.BioMed research international · 2021Review
- Potential Repurposed Therapeutics and New Vaccines against COVID-19 and Their Clinical Status.SLAS discovery : advancing life sciences R & D · 2020Article
- Electroacupuncture pre‑conditioning protects from lung injury induced by limb ischemia/reperfusion through TLR4 and NF‑κB in rats.Molecular medicine reports · 2020Article
- GM-CSF-based treatments in COVID-19: reconciling opposing therapeutic approaches.Nature reviews. Immunology · 2020Review
- Recruiting the innate immune system with GM-CSF to fight viral diseases, including West Nile Virus encephalitis and COVID-19.F1000Research · 2020Article
- Alpha-hemolysin of uropathogenic Escherichia coli induces GM-CSF-mediated acute kidney injury.Mucosal immunology · 2020Article
- TLRs in pulmonary diseases.Life sciences · 2019Review
- Toll-like receptor 4: A promising therapeutic target for pneumonia caused by Gram-negative bacteria.Journal of cellular and molecular medicine · 2019Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Toll-like receptors (TLRs) are required for protective host defense against bacterial pathogens. However, the role of TLRs in regulating lung injury during Gram-negative bacterial pneumonia has not been thoroughly investigated. In this study, experiments were performed to evaluate the role of TLR4 in pulmonary responses against Klebsiella pneumoniae (Kp). Compared with wild-type (WT) (Balb/c) mice, mice with defective TLR4 signaling (TLR4(lps-d) mice) had substantially higher lung bacterial colony-forming units after intratracheal challenge with Kp, which was associated with considerably greater lung permeability and lung cell death. Reduced expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA and protein was noted in lungs and bronchoalveolar lavage fluid of TLR4 mutant mice postintratracheal Kp compared with WT mice, and primary alveolar epithelial cells (AEC) harvested from TLR4(lps-d) mice produced significantly less GM-CSF in vitro in response to heat-killed Kp compared with WT AEC. TLR4(lps-d) AEC underwent significantly more apoptosis in response to heat-killed Kp in vitro, and treatment with GM-CSF protected these cells from apoptosis in response to Kp. Finally, intratracheal administration of GM-CSF in TLR4(lps-d) mice significantly decreased albumin leak, lung cell apoptosis, and bacteremia in Kp-infected mice. Based on these observations, we conclude that TLR4 plays a protective role on lung epithelium during Gram-negative bacterial pneumonia, an effect that is partially mediated by GM-CSF.
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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.