ArticlePloS one2011
Interleukin-6 synthesis in human chondrocytes is regulated via the antagonistic actions of prostaglandin (PG)E2 and 15-deoxy-Δ(12,14)-PGJ2.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 27 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 40 citations in OpenAlex.
- Prostaglandin and myokine involvement in the cyclooxygenase-inhibiting drug enhancement of skeletal muscle adaptations to resistance exercise in older adults.American journal of physiology. Regulatory, integrative and comparative physiology · 2013Trial
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- Dissecting specific Wnt components governing osteogenic differentiation potential by human periodontal ligament stem cells through interleukin-6.Scientific reports · 2023Article
- Genetic variants of interleukin 1B and 6 are associated with clinical outcome of surgically treated lumbar degenerative disc disease.BMC musculoskeletal disorders · 2022Article
- Fatty Acids and Oxylipins in Osteoarthritis and Rheumatoid Arthritis-a Complex Field with Significant Potential for Future Treatments.Current rheumatology reports · 2021Review
- Pathophysiological Perspective of Osteoarthritis.Medicina (Kaunas, Lithuania) · 2020Review
- The role of indoleamine 2,3 dioxygenase 1 in the osteoarthritis.American journal of translational research · 2020Review
- The Damage-Associated Molecular Patterns (DAMPs) as Potential Targets to Treat Osteoarthritis: Perspectives From a Review of the Literature.Frontiers in medicine · 2020Review
- Bystander effectors of chondrosarcoma cells irradiated at different LET impair proliferation of chondrocytes.Journal of cell communication and signaling · 2019Article
- Stichopus chloronotus aqueous extract as a chondroprotective agent for human chondrocytes isolated from osteoarthitis articular cartilage in vitro.Cytotechnology · 2019Article
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- Magnesium Ions Inhibit the Expression of Tumor Necrosis Factor α and the Activity of γ-Secretase in a β-Amyloid Protein-Dependent Mechanism in APP/PS1 Transgenic Mice.Frontiers in molecular neuroscience · 2018Article
- Prostaglandin IOncotarget · 2017Article
- MiR-124-3p attenuates hyperphosphorylation of Tau protein-induced apoptosis via caveolin-1-PI3K/Akt/GSK3β pathway in N2a/APP695swe cells.Oncotarget · 2017Article
- Article
- Prostaglandin I₂ Attenuates Prostaglandin E₂-Stimulated Expression of Interferon γ in a β-Amyloid Protein- and NF-κB-Dependent Mechanism.Scientific reports · 2016Article
- The role of cyclooxygenase-2, interleukin-1β and fibroblast growth factor-2 in the activation of matrix metalloproteinase-1 in sheared-chondrocytes and articular cartilage.Scientific reports · 2015Article
- By activating matrix metalloproteinase-7, shear stress promotes chondrosarcoma cell motility, invasion and lung colonization.Oncotarget · 2015Article
- STAT1 is Constitutively Activated in the T/C28a2 Immortalized Juvenile Human Chondrocyte Line and Stimulated by IL-6 Plus Soluble IL-6R.Journal of clinical & cellular immunology · 2015Article
- TLR4 signalling in osteoarthritis--finding targets for candidate DMOADs.Nature reviews. Rheumatology · 2015Review
Corrections and comments
- Retraction · 2024-07-30Concerns/Issues about Image · Copyright Claims · Duplication of/in Image · Euphemisms for Duplication · Investigation by Journal/Publisher · Original Data and/or Images not Provided and/or not Available · Unreliable Data ·
- Retracted
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundElevated levels of interleukin-6 (IL-6), prostaglandin (PG)E(2), PGD(2) and its dehydration end product 15-deoxy-Δ(12,14)-PGJ(2) (15d-PGJ(2)) have been detected in joint synovial fluids from patients with rheumatoid arthritis (RA). PGE(2) directly stimulates IL-6 production in human articular chondrocytes. However, the effects of PGD(2) and 15d-PGJ(2) in the absence or presence of PGE(2) on IL-6 synthesis in human chondrocytes have yet to be determined. It is believed that dysregulated overproduction of IL-6 is responsible for the systemic inflammatory manifestations and abnormal laboratory findings in RA patients. METHODOLOGY/PRINCIPAL
findingsUsing the T/C-28a2 chondrocyte cell line as a model system, we report that exogenous PGE(2) and PGD(2)/15d-PGJ(2) exert antagonistic effects on IL-6 synthesis in human T/C-28a2 chondrocytes. Using a synthesis of sophisticated molecular biology techniques, we determined that PGE(2) stimulates Toll-like receptor 4 (TLR4) synthesis, which is in turn responsible for the activation of the ERK1/2, PI3K/Akt and PKA/CREB pathways that phosphorylate the NF-κB p65 subunit leading to NF-κB activation. Binding of the activated NF-κB p65 subunit to IL-6 promoter induces IL-6 synthesis in human T/C28a2 chondrocytes. PGD(2) or 15d-PGJ(2) concurrently downregulates TLR4 and upregulates caveolin-1, which in turn inhibit the PGE(2)-dependent ERK1/2, PI3-K and PKA activation, and ultimately with NF-κB-dependent IL-6 synthesis in chondrocytes. CONCLUSIONS/SIGNIFICANCE: We have delineated the signaling cascade by which PGE(2) and PGD(2)/15d-PGJ(2) exert opposing effects on IL-6 synthesis in human chondrocytes. Elucidation of the molecular pathway of IL-6 synthesis and secretion by chondrocytes will provide insights for developing strategies to reduce inflammation and pain in RA patients.
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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.