ArticleJournal of immunology (Baltimore, Md. : 1950)2011
Abnormal trafficking and degradation of TLR4 underlie the elevated inflammatory response in cystic fibrosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 93 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.
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Who cites it
93 citing papers in PubMed, 132 citations in OpenAlex.
- The Involvement of MicroRNAs in Innate Immunity and Cystic Fibrosis Lung Disease: A Narrative Review.Current issues in molecular biology · 2026Review
- Human iPSC-derived macrophages for studying intrinsic and extrinsic factors in cystic fibrosis.EXO : beyond the cell · 2026Article
- Review
- Future Perspectives on Targeting the Activated TLR4/NFκB Pathway in Cystic Fibrosis: A Possible Interplay Between Ethnopharmacology and microRNA Therapeutics.Molecules (Basel, Switzerland) · 2025Review
- Molecular Study from the Signaling Pathways of Four PotentialInternational journal of molecular sciences · 2025Article
- Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Article
- METTL3 mediates SOX5 m6A methylation in bronchial epithelial cells to attenuate Th2 cell differentiation in T2 asthma.Heliyon · 2024Article
- CFTR is required for zinc-mediated antibacterial defense in human macrophages.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- miR-146a-3p as a potential novel therapeutic by targeting MBD2 to mediate Th17 differentiation in Th17 predominant neutrophilic severe asthma.Clinical and experimental medicine · 2023Article
- Genome Editing for Cystic Fibrosis.Cells · 2023Review
- CAGE sequencing reveals CFTR-dependent dysregulation of type I IFN signaling in activated cystic fibrosis macrophages.Science advances · 2023Article
- Cystic Fibrosis Bone Disease: The Interplay between CFTR Dysfunction and Chronic Inflammation.Biomolecules · 2023Review
- Use of Fluorescent Chemical Probes in the Study of Toll-like Receptors (TLRs) Trafficking.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Recruited monocytes/macrophages drive pulmonary neutrophilic inflammation and irreversible lung tissue remodeling in cystic fibrosis.Cell reports · 2022Article
- The Impact of Highly Effective Modulator Therapy on Cystic Fibrosis Microbiology and Inflammation.Clinics in chest medicine · 2022Review
- Alternatives to Antibiotics againstAntibiotics (Basel, Switzerland) · 2022Review
- Emerging Concepts in Defective Macrophage Phagocytosis in Cystic Fibrosis.International journal of molecular sciences · 2022Review
- Lipopolysaccharide Accelerates Neuropilin-1 Protein Degradation by Activating the Large GTPase Dynamin-1 in Macrophages.Inflammation · 2022Article
- Recruitment of monocytes primed to express heme oxygenase-1 ameliorates pathological lung inflammation in cystic fibrosis.Experimental & molecular medicine · 2022Article
33 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Morbidity and mortality in cystic fibrosis (CF) are due not only to abnormal epithelial cell function, but also to an abnormal immune response. We have shown previously that macrophages lacking CF transmembrane conductance regulator (CFTR), the gene mutated in CF, contribute significantly to the hyperinflammatory response observed in CF. In this study, we show that lack of functional CFTR in murine macrophages causes abnormal TLR4 subcellular localization. Upon LPS stimulation, CFTR macrophages have prolonged TLR4 retention in the early endosome and reduced translocation into the lysosomal compartment. This abnormal TLR4 trafficking leads to increased LPS-induced activation of the NF-κB, MAPK, and IFN regulatory factor-3 pathways and decreased TLR4 degradation, which affects downregulation of the proinflammatory state. In addition to primary murine cells, mononuclear cells isolated from CF patients demonstrate similar defects in response to LPS. Moreover, specific inhibition of CFTR function induces abnormal TLR4 trafficking and enhances the inflammatory response of wild-type murine cells to LPS. Thus, functional CFTR in macrophages influences TLR4 spatial and temporal localization and perturbs LPS-mediated signaling in both murine CF models and patients with 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.