The SOD mimic MnTM-2-PyP(5+) reduces hyaluronan degradation-induced inflammation in mouse articular chondrocytes stimulated with Fe (II) plus ascorbate
| Autor: | Antonina Pisani, Alberto Calatroni, Angela D'Ascola, Michele Scuruchi, Domenico Puzzolo, Angela Avenoso, Salvatore Campo, Giancarlo Nastasi, Giuseppe M. Campo, Antonio Micali |
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| Rok vydání: | 2013 |
| Předmět: |
Cartilage
Articular Male Metalloporphyrins Cysteamine Iron Interleukin-1beta Nitric Oxide Synthase Type II Inflammation Ascorbic Acid Biochemistry Proinflammatory cytokine Superoxide dismutase Lipid peroxidation Mice chemistry.chemical_compound Chondrocytes Matrix Metalloproteinase 13 medicine Animals RNA Messenger Hyaluronic Acid chemistry.chemical_classification Reactive oxygen species biology Superoxide Dismutase Tumor Necrosis Factor-alpha NF-kappa B Cell Biology Molecular biology Toll-Like Receptor 2 Respiratory burst Molecular Weight Toll-Like Receptor 4 Hyaluronan Receptors Gene Expression Regulation chemistry biology.protein Tumor necrosis factor alpha Lipid Peroxidation medicine.symptom Peptides Reactive Oxygen Species Oxidation-Reduction Peroxynitrite |
| Zdroj: | The International Journal of Biochemistry & Cell Biology. 45:1610-1619 |
| ISSN: | 1357-2725 |
| DOI: | 10.1016/j.biocel.2013.05.007 |
| Popis: | In pathological conditions, oxidative burst generates hyaluronan (HA) fragmentation with a consequent increase in the number of small HA oligosaccharides. These fragments are able to stimulate an inflammatory response in different cell types by activating the CD44 and the toll-like receptors 4 (TLR-4) and 2 (TLR-2). The stimulation of CD44 and TLRs in turn activates the NF-kB which induces the production of several pro-inflammatory mediators that amplify and perpetuate inflammation. We aimed to study the antioxidant effect of the SOD mimic, synthetic manganese porphyrin, Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin (MnTM-2-PyP(5+)) on preventing HA degradation in mouse articular chondrocytes stimulated with Fe (II) plus ascorbate. Fe (II) plus ascorbate stimulation induced oxidative burst confirmed by high levels of hydroxyl radical/peroxynitrite production, increased lipid peroxidation and HA degradation. HA fragments highly induced mRNA expression and the related protein production of CD44, TLR-4 and TLR-2, NF-kB activation and significantly up-regulated the inflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin-1beta (IL-1beta), and other pro-inflammatory mediators, i.e. matrix metalloprotease 13 (MMP-13) and inducible nitric oxide synthase (iNOS). Treatment of cells with MnTM-2-PyP(5+)was able to attenuate oxidative burst, HA degradation and NF-kB activation, and markedly decreased mRNA expression of CD44, and TLRs and the related protein synthesis, as well as the levels of up-regulated inflammatory mediators. Adding a specific HA-blocking peptide (PEP-1) to cells significantly reduced all the inflammatory parameters up-regulated by Fe (II) plus ascorbate, and increased MnTM-2-PyP(5+) activity. These findings suggest that HA degradation plays a key role in the initial inflammatory response of cartilage and antioxidants and could be a useful tool to prevent the propagation of this mechanism. |
| Databáze: | OpenAIRE |
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