Interleukin-1 in combination with oncostatin M up-regulates multiple genes in chondrocytes: Implications for cartilage destruction and repair
| Autor: | Andrew D. Rowan, Carl D. Richards, Tim E. Cawston, H. E. Barksby, J. M. Milner, Wang Hui, Heiko Peters, Ilka Wappler |
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| Rok vydání: | 2006 |
| Předmět: |
Cartilage
Articular medicine.medical_treatment Immunology Oncostatin M Matrix metalloproteinase Biology Chondrocyte Proinflammatory cytokine Extracellular matrix Chondrocytes Rheumatology medicine Humans Immunology and Allergy Pharmacology (medical) RNA Messenger Cells Cultured Oligonucleotide Array Sequence Analysis Cartilage Drug Synergism Up-Regulation Cell biology Drug Combinations medicine.anatomical_structure Cytokine biology.protein Cytokines Inflammation Mediators Signal transduction Chondrogenesis Interleukin-1 |
| Zdroj: | Arthritis & Rheumatism. 54:540-550 |
| ISSN: | 1529-0131 0004-3591 |
| Popis: | Objective To identify the genes up-regulated by interleukin-1 (IL-1) in combination with oncostatin M (OSM) in chondrocytes that may be involved in mechanisms of cartilage repair and degradation. Methods Gene microarray and real-time polymerase chain reaction (PCR) experiments were performed using RNA from SW1353 chondrocytes and primary human articular chondrocytes. Sections prepared from murine joints, injected with adenovirus vectors overexpressing IL-1 and/or OSM, were analyzed by immunohistochemistry for selected proteins. Results The combination of IL-1 and OSM markedly up-regulated the expression of various genes, including matrix metalloproteinases (MMPs), cytokines, chemokines, extracellular matrix components, and genes involved in signal transduction. Real-time PCR confirmed a synergistic induction of several MMPs, activin A, pentraxin 3 (PTX-3), and IL-8. The in vivo findings further indicated that stimulation with IL-1 plus OSM induced protein expression of activin A, PTX-3, and KC (the murine homolog of IL-8), as compared with the changes induced by individual cytokine treatment and unstimulated controls. Conclusion The results confirm that the potent proinflammatory cytokine combination of IL-1 plus OSM synergistically and coordinately up-regulates many genes and several MMPs. Moreover, chondrocytes exhibit a potential repair response following this procatabolic stimulus such that the repair mechanisms are ultimately overwhelmed by degradative processes in the cartilage. This gene-profiling study provides insight into the complex processes that mediate joint disease in the inflammatory arthritides through the coordinated expression of multiple genes. |
| Databáze: | OpenAIRE |
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