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SOD3 reduces inflammatory cell migration by regulating adhesion molecule and cytokine expression
Juha P Laurila1, Lilja E Laatikainen, Maria D Castellone
1Medicity Research Laboratory, University of Turku, Turku, Finland.
Plos One
|June 5, 2009
Summary
Extracellular superoxide dismutase (SOD3) reduces inflammatory cell migration in ischemic injuries. SOD3 selectively prevents monocyte/macrophage infiltration, suggesting its therapeutic potential for inflammatory disorders.
Area of Science:
- Biomedical Science
- Inflammation Research
- Ischemic Injury
Background:
- Inflammatory cell migration in ischemic damage has a dual role, aiding recovery but also causing harm.
- Extracellular superoxide dismutase (SOD3) shows anti-inflammatory effects in ischemia by promoting recovery.
- SOD3's impact on inflammatory mediators and adhesion molecules in vascular lesions requires further characterization.
Purpose of the Study:
- To investigate the effect of SOD3 on inflammatory cell extravasation in vivo.
- To analyze SOD3's response on inflammatory cytokine and adhesion molecule expression.
- To determine SOD3's selective role in mitigating inflammatory cell infiltration during ischemic injury.
Main Methods:
- Studied in vivo models: rat hind limb ischemia and mouse peritonitis.
- Identified migrated cells and analyzed SOD3's effect on cytokine and adhesion molecule expression.
- Quantified changes in specific inflammatory markers (TNFα, IL-1α, IL-6, MIP-2, MCP-1) and adhesion molecules (VCAM, ICAM, P-selectin, E-selectin).
Main Results:
- SOD3 overexpression significantly reduced key inflammatory cytokines (TNFα, IL-1α, IL-6, MIP-2, MCP-1) and adhesion molecules (VCAM, ICAM, P-selectin, E-selectin).
- Mononuclear cell infiltration, particularly CD68+ monocytes and CD3+ T cells, was significantly decreased.
- Granulocyte migration was less affected by SOD3 overexpression.
Conclusions:
- SOD3 exhibits a selective anti-inflammatory role in ischemic damage.
- SOD3 prevents the migration of reactive oxygen-producing monocyte/macrophages, which can exacerbate tissue injury.
- SOD3 presents potential as a therapeutic agent for inflammatory disorders.
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