ArticleProceedings of the National Academy of Sciences of the United States of America2013
NF-κB inhibitor targeted to activated endothelium demonstrates a critical role of endothelial NF-κB in immune-mediated diseases.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 87 citations in OpenAlex.
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- RIPK3 Protects Against Endothelial Activation and Vascular Permeability in a Mouse Model of Ischemia-Reperfusion Injury.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Cholesteatoma: An Updated Review of Molecular Pathogenesis and Potential Therapeutic Directions.Current medicinal chemistry · 2026Review
- Transcriptomic profiling reveals a dramatic inflammatory shift in osteal macrophages during colitis-induced osteoporosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Article
- Article
- Distinct late-stage osteoarthritis profiles identified through NF-κB, TNF-α, and TGF-β-driven synovial inflammation and pain.Scientific reports · 2025Article
- Genetic or therapeutic disruption of the Reelin/Apoer2 signaling pathway improves inflammatory arthritis outcomes.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Decoy oligonucleotides targeting NF-κB: a promising therapeutic approach for inflammatory diseases.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Panduratin A Inhibits TNF Alpha-Stimulated Endothelial Cell Activation Through Suppressing the NF-κB Pathway.Biomolecules · 2024Article
- The role of NF-κB in carcinogenesis of cervical cancer: opportunities and challenges.Molecular biology reports · 2024Review
- Antiseptic Functions of CGK012 against HMGB1-Mediated Septic Responses.International journal of molecular sciences · 2024Article
- NF-κB in biology and targeted therapy: new insights and translational implications.Signal transduction and targeted therapy · 2024Review
- Targeting endothelial vascular cell adhesion molecule-1 in atherosclerosis: drug discovery and development of vascular cell adhesion molecule-1-directed novel therapeutics.Cardiovascular research · 2023Review
- Consensus Gene Network Analysis Identifies the Key Similarities and Differences in Endothelial and Epithelial Cell Dynamics afterInternational journal of molecular sciences · 2023Article
- ISGylation of NF-κBp65 by SCFArteriosclerosis, thrombosis, and vascular biology · 2023Article
- Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis.Biological research · 2023Article
- Targeting the Inside of Cells with Biologicals: Toxin Routes in a Therapeutic Context.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Myeloid lineage cells evince distinct steady-state level of certain gene groups in dependence on hereditary angioedema severity.Frontiers in genetics · 2023Article
- The Sponge-Derived Brominated Compound Aeroplysinin-1 Impairs the Endothelial Inflammatory Response through Inhibition of the NF-κB Pathway.Marine drugs · 2022Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 7 institutions in 2 countries.
Funding
Abstract
Activation of the nuclear transcription factor κB (NF-κB) regulates the expression of inflammatory genes crucially involved in the pathogenesis of inflammatory diseases. NF-κB governs the expression of adhesion molecules that play a pivotal role in leukocyte-endothelium interactions. We uncovered the crucial role of NF-κB activation within endothelial cells in models of immune-mediated diseases using a "sneaking ligand construct" (SLC) selectively inhibiting NF-κB in the activated endothelium. The recombinant SLC1 consists of three modules: (i) an E-selectin targeting domain, (ii) a Pseudomonas exotoxin A translocation domain, and (iii) a NF-κB Essential Modifier-binding effector domain interfering with NF-κB activation. The E-selectin-specific SLC1 inhibited NF-κB by interfering with endothelial IκB kinase 2 activity in vitro and in vivo. In murine experimental peritonitis, the application of SLC1 drastically reduced the extravasation of inflammatory cells. Furthermore, SLC1 treatment significantly ameliorated the disease course in murine models of rheumatoid arthritis. Our data establish that endothelial NF-κB activation is critically involved in the pathogenesis of arthritis and can be selectively inhibited in a cell type- and activation stage-dependent manner by the SLC approach. Moreover, our strategy is applicable to delineating other pathogenic signaling pathways in a cell type-specific manner and enables selective targeting of distinct cell populations to improve effectiveness and risk-benefit ratios of therapeutic interventions.
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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.