ArticleProceedings of the National Academy of Sciences of the United States of America1999
Defining therapeutic targets by using adenovirus: blocking NF-kappaB inhibits both inflammatory and destructive mechanisms in rheumatoid synovium but spares anti-inflammatory mediators.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 209 citations in OpenAlex.
- The Toll-like receptor adaptor proteins MyD88 and Mal/TIRAP contribute to the inflammatory and destructive processes in a human model of rheumatoid arthritis.The American journal of pathology · 2007Trial
- An NF-kB/TNF-alpha signalling feedback loop acts to coordinate tissue regeneration and macrophage behaviour in zebrafish.NPJ Regenerative medicine · 2025Article
- Proteasome Inhibitors: Potential in Rheumatoid Arthritis Therapy?International journal of molecular sciences · 2025Review
- Homoharringtonine: mechanisms, clinical applications and research progress.Frontiers in oncology · 2025Review
- Transcriptomic analysis of the cerebral hippocampal tissue in spontaneously hypertensive rats exposed to acute hypobaric hypoxia: associations with inflammation and energy metabolism.Scientific reports · 2023Article
- PpSP32, the Phlebotomus papatasi immunodominant salivary protein, exerts immunomodulatory effects on human monocytes, macrophages, and lymphocytes.Parasites & vectors · 2023Article
- Cytokine Networks in the Pathogenesis of Rheumatoid Arthritis.International journal of molecular sciences · 2021Review
- CS-semi5 Inhibits NF-κB Activation to Block Synovial Inflammation, Cartilage Loss and Bone Erosion Associated With Collagen-Induced Arthritis.Frontiers in pharmacology · 2021Article
- The One That Got Away: How Macrophage-Derived IL-1β Escapes the Mycolactone-Dependent Sec61 Blockade in Buruli Ulcer.Frontiers in immunology · 2021Article
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- IRAK2 is associated with susceptibility to rheumatoid arthritis.Clinical rheumatology · 2018Article
- Anti-inflammatory effect of hesperidin enhances chondrogenesis of human mesenchymal stem cells for cartilage tissue repair.Journal of inflammation (London, England) · 2018Article
- Brain-derived neurotrophic factor is regulated via MyD88/NF-κB signaling in experimental Streptococcus pneumoniae meningitis.Scientific reports · 2017Article
- Osteopontin stimulates matrix metalloproteinase expression through the nuclear factor-κB signaling pathway in rat temporomandibular joint and condylar chondrocytes.American journal of translational research · 2017Article
- From osteoarthritic synovium to synovial-derived cells characterization: synovial macrophages are key effector cells.Arthritis research & therapy · 2016Article
- Celastrol and Its Role in Controlling Chronic Diseases.Advances in experimental medicine and biology · 2016Article
- Lipid peroxidation-mediated inflammation promotes cell apoptosis through activation of NF-κB pathway in rheumatoid arthritis synovial cells.Mediators of inflammation · 2015Article
- HMGB1-LPS complex promotes transformation of osteoarthritis synovial fibroblasts to a rheumatoid arthritis synovial fibroblast-like phenotype.Cell death & disease · 2014Article
- Resveratrol pretreatment attenuates the isoflurane-induced cognitive impairment through its anti-inflammation and -apoptosis actions in aged mice.Journal of molecular neuroscience : MN · 2014Article
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Authors and funding
4 authors.
Funding
Abstract
The role of the transcription factor NF-kappaB in the pathogenesis of rheumatoid arthritis has long been a subject of controversy. We used an adenoviral technique of blocking NF-kappaB through overexpression of the inhibitory subunit IkappaBalpha, which has the advantage that it can be used in the diseased tissue itself, with >90% of the synovial macrophages, fibroblasts, and T cells infected. We found that the spontaneous production of tumor necrosis factor alpha and other pro-inflammatory cytokines is NF-kappaB-dependent in rheumatoid synovial tissue, in contrast to the main anti-inflammatory mediators, like IL-10 and -11, and the IL-1 receptor antagonist. Of even more interest, IkappaBalpha overexpression inhibited the production of matrix metalloproteinases 1 and 3 while not affecting their tissue inhibitor. Blocking NF-kappaB in the rheumatoid joint thus has a very beneficial profile, reducing both the inflammatory response and the tissue destruction. The adenoviral technique described here has widespread applicability, allowing rapid testing of the effects of blocking a potential therapeutic target in either cultures of normal cells or in the diseased tissue itself.
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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.