ArticleThe Journal of biological chemistry2010
Shear-induced interleukin-6 synthesis in chondrocytes: roles of E prostanoid (EP) 2 and EP3 in cAMP/protein kinase A- and PI3-K/Akt-dependent NF-kappaB activation.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 78 citations in OpenAlex.
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- Role of the portal system in liver regeneration: From molecular mechanisms to clinical management.Liver research (Beijing, China) · 2024Review
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- The role of mechanobiology in bone and cartilage model systems in characterizing initiation and progression of osteoarthritis.APL bioengineering · 2022Review
- Effects of mechanical stimulation on metabolomic profiles of SW1353 chondrocytes: shear and compression.Biology open · 2022Article
- Chondrocytes from Osteoarthritis Patients Adopt Distinct Phenotypes in Response to Central TInternational journal of molecular sciences · 2021Article
- A 3D human adipose tissue model within a microfluidic device.Lab on a chip · 2021Article
- TAS2R16 Activation Suppresses LPS-Induced Cytokine Expression in Human Gingival Fibroblasts.Frontiers in immunology · 2021Article
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
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- Inhibition of Ep3 attenuates migration and promotes apoptosis of non-small cell lung cancer cells via suppression of TGF-β/Smad signaling.Oncology letters · 2018Article
- β-Catenin and interleukin-1β-dependent chemokine (C-X-C motif) ligand 10 production drives progression of disease in a mouse model of congenital hepatic fibrosis.Hepatology (Baltimore, Md.) · 2018Article
- 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
- Inhibitory effect of JAK inhibitor on mechanical stress-induced protease expression by human articular chondrocytes.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- Magnesium ion influx reduces neuroinflammation in Aβ precursor protein/Presenilin 1 transgenic mice by suppressing the expression of interleukin-1β.Cellular & molecular immunology · 2017Article
- Prostate Cancer and Aspirin Use: Synopsis of the Proposed Molecular Mechanisms.Frontiers in pharmacology · 2017Review
- Article
- Prostaglandin E2/cyclooxygenase pathway in human skeletal muscle: influence of muscle fiber type and age.Journal of applied physiology (Bethesda, Md. : 1985) · 2016Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Mechanical overloading of cartilage producing hydrostatic stress, tensile strain, and fluid flow can adversely affect chondrocyte function and precipitate osteoarthritis (OA). Application of high fluid shear stress to chondrocytes recapitulates the earmarks of OA, as evidenced by the release of pro-inflammatory mediators, matrix degradation, and chondrocyte apoptosis. Elevated levels of cyclooxygenase-2 (COX-2), prostaglandin (PG) E(2), and interleukin (IL)-6 have been reported in OA cartilage in vivo, and in shear-activated chondrocytes in vitro. Although PGE(2) positively regulates IL-6 synthesis in chondrocytes, the underlying signaling pathway of shear-induced IL-6 expression remains unknown. Using the human T/C-28a2 chondrocyte cell line as a model system, we demonstrate that COX-2-derived PGE(2) signals via up-regulation of E prostanoid (EP) 2 and down-regulation of EP3 receptors to raise intracellular cAMP, and activate protein kinase A (PKA) and phosphatidylinositol 3-kinase (PI3-K)/Akt pathways. PKA and PI3-K/Akt transactivate the NF-kappaB p65 subunit via phosphorylation at Ser-276 and Ser-536, respectively. Binding of p65 to the IL-6 promoter elicits IL-6 synthesis in sheared chondrocytes. Selective knockdown of EP2 or ectopic expression of EP3 blocks PKA- and PI3-K/Akt-dependent p65 activation and markedly diminishes shear-induced IL-6 expression. Similar inhibitory effects on IL-6 synthesis were observed by inhibiting PKA, PI3-K, or NF-kappaB using pharmacological and/or genetic interventions. Reconstructing the signaling network regulating shear-induced IL-6 expression in chondrocytes may provide insights for developing therapeutic strategies for arthritic disorders and for culturing artificial cartilage in bioreactors.
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