ArticleThe Journal of biological chemistry2018
Lipopolysaccharide (LPS)-binding protein stimulates CD14-dependent Toll-like receptor 4 internalization and LPS-induced TBK1-IKKϵ-IRF3 axis activation.
Article in The Journal of biological chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 2 of them syntheses that pooled it.
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Who cites it
119 citing papers in PubMed, 2 syntheses or guidelines pooled it, 208 citations in OpenAlex.
- Fructose-Containing Dietary Exposures and Pediatric Atopic Disease: A Review of Epidemiologic Evidence.Nutrients · 2026Pooled it
- Systematic Review of Multi-Omics Approaches to Investigate Toxicological Effects in Macrophages.International journal of molecular sciences · 2020Pooled it
- Effect of probiotic supplementation along with calorie restriction on metabolic endotoxemia, and inflammation markers in coronary artery disease patients: a double blind placebo controlled randomized clinical trial.Nutrition journal · 2021Trial
- A Novel Platform for Fast and Cost-Effective Screening of Immunomodulatory Compounds.Advanced biology · 2026Article
- A polymer that reinforces luminal barrier function and attenuates inflammation in murine colitis.Research square · 2026Article
- LRP1 Activation Promotes Metabolic Reprogramming and Mrc1 Expression to Attenuate LPS-Induced Cognitive Deficits: An Integrated Omics Analysis.CNS neuroscience & therapeutics · 2026Article
- Oral Microbiota and Cardiovascular Diseases: A Study Integrating Genome-Wide Association and 16S rRNA Sequence Analyses.International dental journal · 2026Article
- Genomic Map of Escherichia coli and Single Nucleotide Polymorphism Markers in Colorectal Cancer.Microbial biotechnology · 2026Article
- Defined culture conditions improve functional properties of mature iPSC-derived macrophages for therapeutic screening.Stem cell research & therapy · 2026Article
- Dysregulation of the Gut-Adipose Tissue-Liver Axis: a Possible Mechanism Behind the Relationship Between Metabolic Dysfunction-Associated Steatotic Liver Disease and Type 2 Diabetes.Current diabetes reports · 2026Review
- Anti-Inflammatory Effects of Sesamin-Loaded Nanoparticles in LPS-Stimulated RAW 264.7 Macrophages.Pharmaceutics · 2026Article
- Peptide OH-CATH30 Mitigates Cachexia-Induced Muscle Atrophy via Modulation of TLR4-Associated Inflammation.Journal of cachexia, sarcopenia and muscle · 2026Article
- Interferon Regulatory Factors in Alcohol-Associated Liver Disease: Cell-Type Programs, Danger Signaling, and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Article
- The gut microbiome in colorectal cancer: mechanisms of carcinogenesis and emerging microbiota-targeted therapies.Discover oncology · 2026Review
- Biomarker-based diagnosis of ventilator-associated pneumonia using serum and bronchoalveolar lavage fluid levels of presepsin, procalcitonin, and lipopolysaccharide-binding protein.Frontiers in cellular and infection microbiology · 2026Article
- Processed carp scales as a functional food for sepsis protection: enhancing amino acid content and bioactive peptide profiles.Frontiers in nutrition · 2026Article
- Nanoparticle-Based Drug Delivery Systems for Periodontitis: Antibacterial, Immunomodulatory, and Regenerative Strategies.International journal of nanomedicine · 2026Review
- Pulmonary injury in inflammatory bowel disease: intestinal barrier disruption, gut-lung axis remodeling, and treatment-related lung toxicity.Frontiers in immunology · 2026Review
- Integrating bioinformatics, molecular dynamics simulation and experimental verification to screen diagnostic biomarkers for polyamine metabolism-related osteoarthritis and predict potential drugs.Journal of orthopaedic surgery and research · 2025Article
59 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor 4 (TLR4) is an indispensable immune receptor for lipopolysaccharide (LPS), a major component of the Gram-negative bacterial cell wall. Following LPS stimulation, TLR4 transmits the signal from the cell surface and becomes internalized in an endosome. However, the spatial regulation of TLR4 signaling is not fully understood. Here, we investigated the mechanisms of LPS-induced TLR4 internalization and clarified the roles of the extracellular LPS-binding molecules, LPS-binding protein (LBP), and glycerophosphatidylinositol-anchored protein (CD14). LPS stimulation of CD14-expressing cells induced TLR4 internalization in the presence of serum, and an inhibitory anti-LBP mAb blocked its internalization. Addition of LBP to serum-free cultures restored LPS-induced TLR4 internalization to comparable levels of serum. The secretory form of the CD14 (sCD14) induced internalization but required a much higher concentration than LBP. An inhibitory anti-sCD14 mAb was ineffective for serum-mediated internalization. LBP lacking the domain for LPS transfer to CD14 and a CD14 mutant with reduced LPS binding both attenuated TLR4 internalization. Accordingly, LBP is an essential serum molecule for TLR4 internalization, and its LPS transfer to membrane-anchored CD14 (mCD14) is a prerequisite. LBP induced the LPS-stimulated phosphorylation of TBK1, IKKϵ, and IRF3, leading to IFN-β expression. However, LPS-stimulated late activation of NF-κB or necroptosis were not affected. Collectively, our results indicate that LBP controls LPS-induced TLR4 internalization, which induces TLR adaptor molecule 1 (TRIF)-dependent activation of the TBK1-IKKϵ-IRF3-IFN-β pathway. In summary, we showed that LBP-mediated LPS transfer to mCD14 is required for serum-dependent TLR4 internalization and activation of the TRIF pathway.
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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.