Differential effects of the antioxidant n-acetylcysteine on the production of catabolic mediators in IL-1beta-stimulated human osteoarthritic synoviocytes and chondrocytes
| Autor: | M A Alvarez-Soria, Gabriel Herrero-Beaumont, María A. Contreras-Blasco, Raquel Largo, Jorge A. Roman-Blas, Santos Castañeda |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
medicine.medical_treatment Interleukin-1beta Osteoarthritis Nitric Oxide Chondrocyte Antioxidants Dinoprostone Nitric oxide Proinflammatory cytokine chemistry.chemical_compound Chondrocytes Internal medicine Matrix Metalloproteinase 13 medicine Humans Prostaglandin E2 Cells Cultured Nitrites Pharmacology business.industry Cartilage Synovial Membrane NF-kappa B Osteoarthritis Knee medicine.disease Acetylcysteine Enzyme Activation medicine.anatomical_structure Endocrinology Cytokine chemistry Cyclooxygenase 2 Immunology Synovial membrane Inflammation Mediators Matrix Metalloproteinase 1 business medicine.drug Subcellular Fractions |
| Zdroj: | European journal of pharmacology. 623(1-3) |
| ISSN: | 1879-0712 |
| Popis: | Oxidative stress may play a relevant role in synovial inflammation and subsequently on cartilage damage during osteoarthritis development. We have assessed how the antioxidant N-acetylcysteine (NAC) affects the expression of different proinflammatory and structural mediators in human stimulated osteoarthritic synoviocytes and chondrocytes. Synovial membrane and articular cartilage were obtained from the osteoarthritis knees of patients who underwent joint replacement surgery. In cells stimulated with IL-1beta (10U/mL), the effects of NAC (2mmol/L) were tested at the mean peak plasma level following oral administration of therapeutic doses and its influence on prostaglandin E2 (PGE(2)) production, cyclooxigenase-2 (COX-2) expression, nitric oxide (NO) synthesis, nuclear factor kappa B (NF-kappaB) activation, and metalloproteinase-1 (MMP-1) and metalloproteinase-13 (MMP-13) expression were evaluated. While NAC significantly diminished PGE(2) release and the expression of both COX-2 and MMP-13 protein in IL-1beta-stimulated synoviocytes, it failed to modify their production in stimulated chondrocytes. Likewise, NAC only inhibited IL-1beta-stimulated NF-kappaB activation in synoviocytes. No inhibition of IL-1beta-induced NO synthesis by chondrocytes was observed following NAC incubation, while synoviocytes did not release detectable levels of NO. NAC did not induce changes in MMP-1 protein expression in either IL-1beta-stimulated synoviocytes or chondrocytes. Thus, NAC decreases the synthesis of several catabolic mediators by osteoarthritic synoviocytes, whereas, it failed to produce the same effects in osteoarthritic chondrocytes. Our results suggest that NAC inhibits some oxygen-dependent mechanisms in synoviocytes but not in chondrocytes during osteoarthritis. Therefore, NAC might have a symptomatic effect on the synovium rather than a structural effect on the cartilage in osteoarthritis. |
| Databáze: | OpenAIRE |
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