دورية أكاديمية
In vitro effects of aceclofenac and its metabolites on the production by chondrocytes of inflammatory mediators.
| العنوان: | In vitro effects of aceclofenac and its metabolites on the production by chondrocytes of inflammatory mediators. |
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| المؤلفون: | Henrotin, Yves, de Leval, X., Mathy, Marianne, Mouithys-Mickalad, Ange, Deby, Ginette, Dogné, Jean-Michel, Delarge, J., Reginster, Jean-Yves |
| المصدر: | Inflammation Research, 50 (8), 391-9 (2001) |
| بيانات النشر: | Springer Science & Business Media B.V. |
| سنة النشر: | 2001 |
| المجموعة: | University of Liège: ORBi (Open Repository and Bibliography) |
| مصطلحات موضوعية: | Adult, Aged, 80 and over, Anti-Inflammatory Agents, Non-Steroidal/pharmacology, Cells, Cultured, Chondrocytes/drug effects/metabolism, Cyclooxygenase 1, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors/pharmacology, Cytokines/metabolism, DNA/biosynthesis/genetics, Diclofenac/analogs & derivatives/pharmacology, Dinoprostone/metabolism, Humans, Inflammation Mediators/metabolism, Interleukin-1/biosynthesis/genetics, Isoenzymes/metabolism, Membrane Proteins, Middle Aged, Nitric Oxide/metabolism, Nitric Oxide Synthase/biosynthesis/genetics, Nitric Oxide Synthase Type II, Prostaglandin-Endoperoxide Synthases/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Human health sciences, Rheumatology, Sciences de la santé humaine |
| الوصف: | peer reviewed ; OBJECTIVES: To investigate the mechanisms of action underlying the anti-inflammatory action of aceclofenac in vivo, we studied in vitro the effect of aceclofenac and its main metabolite, 4'-hydroxyaceclofenac, in comparison with diclofenac, another metabolite, on cyclooxygenases activity as well as interleukin-1beta, -6 and -8, nitric oxide, and prostaglandin E2 production by human osteoarthritic and normal articular chondrocytes. METHODS: Enzymatically isolated human chondrocytes were cultured for 72 h in the absence or presence of interleukin-1beta (IL-1beta) or lipopolysacharride (LPS) and with or without increased amounts (1 to 30 microM) of aceclofenac or metabolites. The production of different cytokines was measured by Enzyme Amplified Sensitivity Immunoassays (EASIA). Prostaglandin E2 was quantified by a specific radioimmunoassay. Nitrite and nitrate concentrations in the culture supernatants were determined by spectrophotometric method based upon the Griess reaction. Cyclooxygenase-2, inducible NO synthase and IL-1beta gene expression were quantified by reverse transcription of mRNA followed by real time and quantitative polymerase chain reaction. Finally, cyclooxygenase inhibitory potency of the drugs was also tested in both a cell-free system using purified ovine cyclooxygenase-1 and -2 (COX-1 and COX-2) and at a cellular level using human whole blood assay. RESULTS: We have demonstrated that aceclofenac, 4'-hydroxyaceclofenac and diclofenac significantly decreased interleukin-6 production at concentrations ranged among 1 to 30 microM and fully blocked prostaglandin E2 synthesis by IL-1beta- or LPS-stimulated human chondrocytes. Aceclofenac and diclofenac had no effect on interleukin-8 production while 4'-hydroxyaceclofenac slightly decreased this parameter at the highest dose (30 microM). Aceclofenac was without effect on IL-1beta- or LPS-stimulated nitric oxide production. At 30 microM, 4'-hydroxyaceclofenac inhibited both IL-1beta or LPS-stimulated nitric oxide production while ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 1023-3830 1420-908X |
| العلاقة: | urn:issn:1023-3830; urn:issn:1420-908X; https://orbi.uliege.be/handle/2268/10412Test; info:hdl:2268/10412; scopus-id:2-s2.0-0034887381; info:pmid:11556519 |
| DOI: | 10.1007/PL00000261 |
| الإتاحة: | https://doi.org/10.1007/PL00000261Test https://orbi.uliege.be/handle/2268/10412Test |
| حقوق: | restricted access ; http://purl.org/coar/access_right/c_16ecTest ; info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsbas.45225EF7 |
| قاعدة البيانات: | BASE |
| تدمد: | 10233830 1420908X |
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| DOI: | 10.1007/PL00000261 |