SOD3 Reduces Inflammatory Cell Migration by Regulating Adhesion Molecule and Cytokine Expression
Open Access
- 4 June 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (6), e5786
- https://doi.org/10.1371/journal.pone.0005786
Abstract
Inflammatory cell migration characteristic of ischemic damages has a dual role providing the tissue with factors needed for tissue injury recovery simultaneously causing deleterious development depending on the quality and the quantity of infiltrated cells. Extracellular superoxide dismutase (SOD3) has been shown to have an anti-inflammatory role in ischemic injuries where it increases the recovery process by activating mitogen signal transduction and increasing cell proliferation. However, SOD3 derived effects on inflammatory cytokine and adhesion molecule expression, which would explain reduced inflammation in vascular lesions, has not been properly characterized. In the present work the effect of SOD3 on the inflammatory cell extravasation was studied in vivo in rat hind limb ischemia and mouse peritonitis models by identifying the migrated cells and analyzing SOD3-derived response on inflammatory cytokine and adhesion molecule expression. SOD3 overexpression significantly reduced TNFα, IL1α, IL6, MIP2, and MCP-1 cytokine and VCAM, ICAM, P-selectin, and E-selectin adhesion molecule expressions in injured tissues. Consequently the mononuclear cell, especially CD68+ monocyte and CD3+ T cell infiltration were significantly decreased whereas granulocyte migration was less affected. According to our data SOD3 has a selective anti-inflammatory role in ischemic damages preventing the migration of reactive oxygen producing monocyte/macrophages, which in excessive amounts could potentially further intensify the tissue injuries therefore suggesting potential for SOD3 in treatment of inflammatory disorders.This publication has 68 references indexed in Scilit:
- NADPH Oxidase-Dependent Signaling in Endothelial Cells: Role in Physiology and PathophysiologyAntioxidants and Redox Signaling, 2009
- Extracellular Superoxide Dismutase Is a Growth Regulatory Mediator of Tissue Injury RecoveryMolecular Therapy, 2009
- Adaptation to chronic hypoxia involves immune cell invasion and increased expression of inflammatory cytokines in rat carotid bodyAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Dexamethasone Inhibits High Glucose–, TNF-α–, and IL-1β–Induced Secretion of Inflammatory and Angiogenic Mediators from Retinal Microvascular PericytesInvestigative Ophthalmology & Visual Science, 2008
- Long-term cardiovascular effects of neonatal dexamethasone treatment: hemodynamic follow-up by left ventricular pressure-volume loops in ratsJournal of Applied Physiology, 2008
- Getting to the site of inflammation: the leukocyte adhesion cascade updatedNature Reviews Immunology, 2007
- Delivery of antioxidative enzyme genes protects against ischemia/reperfusion–induced liver injury in miceLiver Transplantation, 2006
- Alternative activation of macrophagesNature Reviews Immunology, 2003
- TNFα Activates c-Jun Amino Terminal Kinase through p47phoxExperimental Cell Research, 2002
- Reduction of myocardial infarct size by neutrophil depletion: Effect of duration of occlusionAmerican Heart Journal, 1986