Cu/Zn Superoxide Dismutase Plays Important Role in Immune Response
| Autor: | Catherine Harris-Cerruti, Nava Nevo, Vered Ziv, Moshe Marikovsky, Ori Mahler |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Lipopolysaccharides
Male Vascular Endothelial Growth Factor A Administration Oral Endothelial Growth Factors Pharmacology Matrix metalloproteinase Antioxidants Mice Disulfiram Immunology and Allergy Hypersensitivity Delayed Cells Cultured chemistry.chemical_classification Lymphokines Mice Inbred BALB C Mitogen-Activated Protein Kinase 3 Vascular Endothelial Growth Factors Anti-Inflammatory Agents Non-Steroidal Up-Regulation Vascular endothelial growth factor A Biochemistry Intercellular Signaling Peptides and Proteins Female Mitogen-Activated Protein Kinases medicine.symptom Transgene Immunology Mice Transgenic Inflammation Immune system In vivo Extracellular medicine Animals Humans Collagenases Reactive oxygen species Superoxide Dismutase Tumor Necrosis Factor-alpha Macrophage Activation Arthritis Experimental Rats Enzyme Activation Mice Inbred C57BL chemistry Rats Inbred Lew Macrophages Peritoneal Copper |
| Zdroj: | The Journal of Immunology. 170:2993-3001 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Activation of macrophages leads to the secretion of cytokines and enzymes that shape the inflammatory response and increase metabolic processes. This, in turn, results in increased production of reactive oxygen species. The role of Cu/Zn superoxide dismutase (SOD-1), an important enzyme in cellular oxygen metabolism, was examined in activated peritoneal elicited macrophages (PEM) and in several inflammatory processes in vivo. LPS and TNF-α induced SOD-1 in PEM. SOD-1 induction by LPS was mainly via extracellular signal-regulated kinase-1 activation. Transgenic mice overexpressing SOD-1 demonstrated a significant increase in the release of TNF-α and of the metalloproteinases MMP-2 and MMP-9 from PEM. Disulfiram (DSF), an inhibitor of SOD-1, strongly inhibited the release of TNF-α, vascular endothelial growth factor, and MMP-2 and MMP-9 from cultured activated PEM. These effects were prevented by addition of antioxidants, further indicating involvement of reactive oxygen species. In vivo, transgenic mice overexpressing SOD-1 demonstrated a 4-fold increase in serum TNF-α levels and 2-fold stronger delayed-type hypersensitivity reaction as compared with control nontransgenic mice. Conversely, oral administration of DSF lowered TNF-α serum level by 4-fold, lowered the delayed-type hypersensitivity response in a dose-dependent manner, and significantly inhibited adjuvant arthritis in Lewis rats. The data suggest an important role for SOD-1 in inflammation, establish DSF as a potential inhibitor of inflammation, and raise the possibility that regulation of SOD-1 activity may be important in the treatment of immune-dependent pathologies. |
| Databáze: | OpenAIRE |
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