ArticleAmerican journal of physiology. Lung cellular and molecular physiology2013
Toll-like receptor 4 is not targeted to the lysosome in cystic fibrosis airway epithelial cells.
Article in American journal of physiology. Lung cellular and molecular physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Macrophage SH3 domain‑containing GRB2‑like protein B1 is required for Rab7‑mediated mitophagy in inflammation during sea water drowning acute lung injury.International journal of molecular medicine · 2026Article
- Future Perspectives on Targeting the Activated TLR4/NFκB Pathway in Cystic Fibrosis: A Possible Interplay Between Ethnopharmacology and microRNA Therapeutics.Molecules (Basel, Switzerland) · 2025Review
- Genetic characterization of Tibetan pigs adapted to high altitude under natural selection based on a large whole-genome dataset.Scientific reports · 2024Article
- A Splice Switch in SIGIRR Causes a Defect of IL-37-Dependent Anti-Inflammatory Activity in Cystic Fibrosis Airway Epithelial Cells.International journal of molecular sciences · 2022Article
- TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling.Cellular and molecular life sciences : CMLS · 2021Review
- Are cystic fibrosis mutation carriers a potentially highly vulnerable group to COVID-19?Journal of cellular and molecular medicine · 2020Article
- Dysregulated signalling pathways in innate immune cells with cystic fibrosis mutations.Cellular and molecular life sciences : CMLS · 2020Review
- Article
- Killing of Pseudomonas aeruginosa by Chicken Cathelicidin-2 Is Immunogenically Silent, Preventing Lung InflammationInfection and immunity · 2017Article
- Ezrin links CFTR to TLR4 signaling to orchestrate anti-bacterial immune response in macrophages.Scientific reports · 2017Article
- Connectivity mapping (ssCMap) to predict A20-inducing drugs and their antiinflammatory action in cystic fibrosis.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Induction of the inflammatory regulator A20 by gibberellic acid in airway epithelial cells.British journal of pharmacology · 2016Article
- Current Concepts and Controversies in Innate Immunity of Cystic Fibrosis Lung Disease.Journal of innate immunity · 2016Review
- Cystic Fibrosis Lung Immunity: The Role of the Macrophage.Journal of innate immunity · 2016Review
- Pharmacological modulation of the AKT/microRNA-199a-5p/CAV1 pathway ameliorates cystic fibrosis lung hyper-inflammation.Nature communications · 2015Article
- Recent advances in understanding and managing cystic fibrosis transmembrane conductance regulator dysfunction.F1000prime reports · 2015Review
- Lipopolysaccharides may aggravate apoptosis through accumulation of autophagosomes in alveolar macrophages of human silicosis.Autophagy · 2015Article
- Cystic Fibrosis from Laboratory to Bedside: The Role of A20 in NF-κB-Mediated Inflammation.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2015Review
- Rhinovirus Load Is High despite Preserved Interferon-β Response in Cystic Fibrosis Bronchial Epithelial Cells.PloS one · 2015Article
- Lung cell-specific modulation of LPS-induced TLR4 receptor and adaptor localization.Communicative & integrative biology · 2014Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
The innate immune response to bacterial infection is mediated through Toll-like receptors (TLRs), which trigger tightly regulated signaling cascades through transcription factors including NF-κB. LPS activation of TLR4 triggers internalization of the receptor-ligand complex which is directed toward lysosomal degradation or endocytic recycling. Cystic fibrosis (CF) patients display a robust and uncontrolled inflammatory response to bacterial infection, suggesting a defect in regulation. This study examined the intracellular trafficking of TLR4 in CF and non-CF airway epithelial cells following stimulation with LPS. We employed cells lines [16hBE14o-, CFBE41o- (CF), and CFTR-complemented CFBE41o-] and confirmed selected experiments in primary nasal epithelial cells from non-CF controls and CF patients (F508del homozygous). In control cells, TLR4 expression (surface and cytoplasmic) was reduced after LPS stimulation but remained unchanged in CF cells and was accompanied by a heightened inflammatory response 24 h after stimulation. All cells expressed markers of the early (EEA1) and late (Rab7b) endosomes at basal levels. However, only CF cells displayed persistent expression of Rab7b following LPS stimulation. Rab7 variants may directly internalize bacteria to the Golgi for recycling or to the lysosome for degradation. TLR4 colocalized with the lysosomal marker LAMP1 in 16 hBE14o- cells, suggesting that TLR4 is targeted for lysosomal degradation in these cells. However, this colocalization was not observed in CFBE41o- cells, where persistent expression of Rab7 and release of proinflammatory cytokines was detected. Consistent with the apparent inability of CF cells to target TLR4 toward the lysosome for degradation, we observed persistent surface and cytoplasmic expression of this pathogen recognition receptor. This defect may account for the prolonged cycle of chronic inflammation associated with CF.
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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.