ArticleArthritis & rheumatology (Hoboken, N.J.)2016
Regulation of Transforming Growth Factor β-Activated Kinase Activation by Epigallocatechin-3-Gallate in Rheumatoid Arthritis Synovial Fibroblasts: Suppression of K(63) -Linked Autoubiquitination of Tumor Necrosis Factor Receptor-Associated Factor 6.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Molecular insights into phytochemicals exhibiting anti-arthritic activity: systematic review : John Di Battista.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2021Pooled it
- Neurotensin modulation of immune and oxido-inflammatory homeostasis targeting TGF-β activated kinase 1/Nuclear factor-kappa βeta pathway: an integrated in vivo and in silico study.Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences · 2026Article
- In Silico Exploration of Natural Antioxidants for Sepsis Drug Discovery.Molecules (Basel, Switzerland) · 2025Article
- Rheumatoid arthritis-recent advances in pathogenesis and the anti-inflammatory effect of plant-derived COX inhibitors.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Potential mechanism of tea for treating osteoporosis, osteoarthritis, and rheumatoid arthritis.Frontiers in medicine · 2024Review
- Epigallocatechin-3-Gallate Therapeutic Potential in Cancer: Mechanism of Action and Clinical Implications.Molecules (Basel, Switzerland) · 2023Review
- Inhibition of Cancer Development by Natural Plant Polyphenols: Molecular Mechanisms.International journal of molecular sciences · 2023Review
- Phytotherapeuthics Affecting the IL-1/IL-17/G-CSF Axis: A Complementary Treatment Option for Hidradenitis Suppurativa?International journal of molecular sciences · 2022Review
- Penta-o-galloyl-beta-d-Glucose (PGG) inhibits inflammation in human rheumatoid arthritis synovial fibroblasts and rat adjuvant-induced arthritis model.Frontiers in immunology · 2022Article
- DNA Methylation of T Lymphocytes as a Therapeutic Target: Implications for Rheumatoid Arthritis Etiology.Frontiers in immunology · 2022Review
- Takinib Inhibits Inflammation in Human Rheumatoid Arthritis Synovial Fibroblasts by Targeting the Janus Kinase-Signal Transducer and Activator of Transcription 3 (JAK/STAT3) Pathway.International journal of molecular sciences · 2021Article
- Regulation of Synovial Inflammation and Tissue Destruction by Guanylate Binding Protein 5 in Synovial Fibroblasts From Patients With Rheumatoid Arthritis and Rats With Adjuvant-Induced Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2021Article
- EGCG, a Green Tea Catechin, as a Potential Therapeutic Agent for Symptomatic and Asymptomatic SARS-CoV-2 Infection.Molecules (Basel, Switzerland) · 2021Review
- Suppression of monosodium urate crystal-induced inflammation by inhibiting TGF-β-activated kinase 1-dependent signaling: role of the ubiquitin proteasome system.Cellular & molecular immunology · 2021Article
- Ets-2 Propagates IL-6 Trans-Signaling Mediated Osteoclast-Like Changes in Human Rheumatoid Arthritis Synovial Fibroblast.Frontiers in immunology · 2021Article
- TWIST1-MicroRNA-10a-MAP3K7 Axis Ameliorates Synovitis of Osteoarthritis in Fibroblast-like Synoviocytes.Molecular therapy. Nucleic acids · 2020Article
- Current and novel therapeutic targets in the treatment of rheumatoid arthritis.Inflammopharmacology · 2020Review
- TAK1: a potent tumour necrosis factor inhibitor for the treatment of inflammatory diseases.Open biology · 2020Review
- Mechanism by which TRAF6 Participates in the Immune Regulation of Autoimmune Diseases and Cancer.BioMed research international · 2020Review
- Multilevel structure-activity profiling reveals multiple green tea compound families that each modulate ubiquitin-activating enzyme and ubiquitination by a distinct mechanism.Scientific reports · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveTransforming growth factor β-activated kinase 1 (TAK1) is a key MAPKKK family protein in interleukin-1β (IL-1β), tumor necrosis factor (TNF), and Toll-like receptor signaling. This study was undertaken to examine the posttranslational modification of TAK1 and its therapeutic regulation in rheumatoid arthritis (RA).
methodsThe effect of TAK1, IL-1 receptor-associated kinase 1 (IRAK-1), and TNF receptor-associated factor 6 (TRAF6) inhibition was evaluated in IL-1β-stimulated human RA synovial fibroblasts (RASFs). Western blotting, immunoprecipitation, and 20S proteasome assay were used to study the ubiquitination process in RASFs. The efficacy of epigallocatechin-3-gallate (EGCG), a potent antiinflammatory molecule, in regulating these processes in RASFs was evaluated. Molecular docking was performed to examine the interaction of EGCG with human TAK1, IRAK-1, and TRAF6. These findings were confirmed using a rat model of adjuvant-induced arthritis (AIA).
resultsInhibition of TAK1, but not IRAK-1 or TRAF6, completely abrogated IL-1β-induced IL-6 and IL-8 synthesis in RASFs. EGCG inhibited TAK1 phosphorylation at Thr(184/187) and occupied the C(174) position, an ATP-binding site, to inhibit its kinase activity. EGCG pretreatment also inhibited K(63) -linked autoubiquitination of TRAF6, a posttranslational modification essential for TAK1 autophosphorylation, by forming a stable H bond at the K(124) position on TRAF6. Furthermore, EGCG enhanced proteasome-associated deubiquitinase expression to rescue proteins from proteasomal degradation. Western blot analyses of joint homogenates from rats with AIA showed a significant increase in K(48) -linked polyubiquitination, TAK1 phosphorylation, and TRAF6 expression when compared to naive rats. Administration of EGCG (50 mg/kg/day) for 10 days ameliorated AIA in rats by reducing TAK1 phosphorylation and K(48) -linked polyubiquitination.
conclusionOur findings provide a rationale for targeting TAK1 for the treatment of RA with EGCG.
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