scholarly journals Superoxide Dismutase 3 Limits Collagen-Induced Arthritis in the Absence of Phagocyte Oxidative Burst

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Tiina Kelkka ◽  
Juha Petteri Laurila ◽  
Outi Sareila ◽  
Peter Olofsson ◽  
Mikko Olavi Laukkanen ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Oxidative Burst ◽  
Adenoviral Vector ◽  
Extracellular Superoxide Dismutase ◽  
Wild Type ◽  
Collagen Induced Arthritis ◽  
Regulatory Subunits ◽  
Superoxide Dismutase 3 ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Extracellular superoxide dismutase (SOD3), an enzyme mediating dismutation of superoxide into hydrogen peroxide, has been shown to reduce inflammation by inhibiting macrophage migration into injured tissues. In inflamed tissues, superoxide is produced by the phagocytic NOX2 complex, which consists of the catalytic subunit NOX2 and several regulatory subunits (e.g., NCF1). To analyze whether SOD3 can regulate inflammation in the absence of functional NOX2 complex, we injected an adenoviral vector overexpressing SOD3 directly into the arthritic paws ofNcf1*/*mice with collagen-induced arthritis. SOD3 reduced arthritis severity in both oxidative burst-deficientNcf1*/*mice and also in wild-type mice. The NOX2 complex independent anti-inflammatory effect of SOD3 was further characterized in peritonitis, and SOD3 was found to reduce macrophage infiltration independently of NOX2 complex functionality. We conclude that the SOD3-mediated anti-inflammatory effect on arthritis and peritonitis operates independently of NOX2 complex derived oxidative burst.

scholarly journals Anti‐inflammatory effect of omega unsaturated fatty acids and dialysable leucocyte extracts on collagen‐induced arthritis in DBA/1 mice

2020 ◽  
Vol 101 (1-2) ◽  
pp. 55-64
Author(s):  
Pamela I. Pérez‐Martínez ◽  
Oscar Rojas‐Espinosa ◽  
Víctor G. Hernández‐Chávez ◽  
Patricia Arce‐Paredes ◽  
Sergio Estrada‐Parra
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Collagen Induced Arthritis ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis

2002 ◽  
Vol 282 (4) ◽  
pp. L719-L726 ◽  
Author(s):  
Russell P. Bowler ◽  
Mike Nicks ◽  
Karrie Warnick ◽  
James D. Crapo
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Pulmonary Fibrosis ◽  
Lung Injury ◽  
Immunohistochemical Staining ◽  
Extracellular Superoxide Dismutase ◽  
Wild Type ◽  
Injured Lung ◽  
Intracellular Oxidative Stress

Bleomycin administration results in well-described intracellular oxidative stress that can lead to pulmonary fibrosis. The role of alveolar interstitial antioxidants in this model is unknown. Extracellular superoxide dismutase (EC-SOD) is the primary endogenous extracellular antioxidant enzyme and is abundant in the lung. We hypothesized that EC-SOD plays an important role in attenuating bleomycin-induced lung injury. Two weeks after intratracheal bleomycin administration, we found that wild-type mice induced a 106 ± 25% increase in lung EC-SOD. Immunohistochemical staining revealed that a large increase in EC-SOD occurred in injured lung. Using mice that overexpress EC-SOD specifically in the lung, we found a 53 ± 14% reduction in bleomycin-induced lung injury assessed histologically and a 17 ± 6% reduction in lung collagen content 2 wk after bleomycin administration. We conclude that EC-SOD plays an important role in reducing the magnitude of lung injury from extracellular free radicals after bleomycin administration.

scholarly journals Dual AAV/IL-10 Plus STAT3 Anti-Inflammatory Gene Delivery Lowers Atherosclerosis in LDLR KO Mice, but without Increased Benefit

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Maohua Cao ◽  
Junaid A. Khan ◽  
Bum-Yong Kang ◽  
Jawahar L. Mehta ◽  
Paul L. Hermonat
Keyword(s):  
Plasma Cholesterol ◽  
Signal Transduction Pathway ◽  
Wild Type ◽  
Cholesterol Levels ◽  
Tail Vein Injection ◽  
Lower Blood ◽  
Aortic Wall Thickness ◽  
Adenoassociated Virus ◽  
Anti Inflammatory ◽  
Inflammatory Effect

Both IL-10 and STAT3 are in the same signal transduction pathway, with IL-10-bound IL10 receptor (R) acting through STAT3 for anti-inflammatory effect. To investigate possible therapeutic synergism, we delivered both full-length wild-type human (h) STAT3 and hIL-10 genes by separate adenoassociated virus type 8 (AAV8) tail vein injection into LDLR KO on HCD. Compared to control Neo gene-treated animals, individual hSTAT3 and hIL-10 delivery resulted in significant reduction in atherogenesis, as determined by larger aortic lumen size, thinner aortic wall thickness, and lower blood velocity (all statistically significant). However, dual hSTAT3/hIL-10 delivery offered no improvement in therapeutic effect. Plasma cholesterol levels in dual hSTAT3/hIL-10-treated animals were statistically higher compared to hIL-10 alone. While no advantage was seen in this case, we consider that the dual gene approach has intrinsic merit, but properly chosen partnered genes must be used.

scholarly journals Protective anti-inflammatory effect of ADAMTS13 on myocardial ischemia/reperfusion injury in mice

Blood ◽  
2012 ◽  
Vol 120 (26) ◽  
pp. 5217-5223 ◽  
Author(s):  
Simon F. De Meyer ◽  
Alexander S. Savchenko ◽  
Michael S. Haas ◽  
Daphne Schatzberg ◽  
Michael C. Carroll ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Myocardium ◽  
Wild Type ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Anti Inflammatory ◽  
Myocardial Ischemia Reperfusion ◽  
Inflammatory Effect

Abstract Coronary heart disease is a major cause of death in the western world. Although essential for successful recovery, reperfusion of ischemic myocardium is inevitably associated with reperfusion injury. To investigate a potential protective role of ADAMTS13, a protease cleaving von Willebrand factor multimers, during myocardial ischemia/reperfusion, we used a mouse model of acute myocardial infarction. We found that Adamts13−/− mice developed larger myocardial infarctions than wild-type control mice, whereas treatment of wild-type mice with recombinant human ADAMTS13 (rhADAMTS13) led to smaller infarctions. The protective effect of ADAMTS13 was further confirmed by a significant reduction of cardiac troponin-I release and less myocardial apoptosis in mice that received rhADAMTS13 compared with controls. Platelets adherent to the blood vessel wall were observed in few areas in the heart samples from mice treated with vehicle and were not detected in samples from mice treated with rhADAMTS13. However, we observed a 9-fold reduction in number of neutrophils infiltrating ischemic myocardium in mice that were treated with rhADAMTS13, suggesting a potent anti-inflammatory effect of ADAMTS13 during heart injury. Our data show that ADAMTS13 reduces myocardial ischemia/reperfusion injury in mice and indicate that rhADAMTS13 could be of therapeutic value to limit myocardial ischemia/reperfusion injury.

scholarly journals Protective effect of extracellular superoxide dismutase on endothelial function during aging

2009 ◽  
Vol 296 (6) ◽  
pp. H1920-H1925 ◽  
Author(s):  
Donald D. Lund ◽  
Yi Chu ◽  
Jordan D. Miller ◽  
Donald D. Heistad
Keyword(s):  
Superoxide Dismutase ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Ex Vivo ◽  
Vascular Dysfunction ◽  
Extracellular Superoxide Dismutase ◽  
Mrna Levels ◽  
Wild Type ◽  
Vasomotor Function ◽  
Old Mice

Endothelial vasomotor function decreases with increasing age. Extracellular superoxide dismutase (ecSOD) protects against vascular dysfunction in several disease states. The purpose of this study was to determine whether endogenous ecSOD protects against endothelial dysfunction in old mice. Vasomotor function of the aorta was studied ex vivo in wild-type (ecSOD+/+) and ecSOD-deficient (ecSOD−/−) mice at 11 (adult) and 29 (old) mo of age. Maximal relaxation to acetylcholine (10−4 M) was impaired in vessels from adult ecSOD−/− mice [75 ± 3% (mean ± SE)] compared with wild-type mice (89 ± 2%, P < 0.05). Maximal relaxation to acetylcholine (10−4 M) was profoundly impaired in aorta from old ecSOD−/− mice (45 ± 5%) compared with wild-type mice (75 ± 4%, P < 0.05). There was a significant correlation between expression of ecSOD and maximal relaxation to acetylcholine in adult and old mice. Tempol (1 mM), a scavenger of superoxide, improved relaxation in response to acetylcholine (63 ± 8%) in old ecSOD−/− mice ( P < 0.05), but not wild-type mice (75 ± 4%). Maximal relaxation to sodium nitroprusside was similar in aorta from adult and old wild-type and ecSOD−/− mice. Quantitative RT-PCR showed a decrease in mRNA levels of ecSOD and catalase in aorta of old mice and an increase in levels of TNFα and Nox-4 in aorta of old mice compared with adult mice. The findings support the hypothesis that impaired antioxidant mechanisms may contribute to cumulative increases in oxidative stress and impaired endothelial function in old mice. In conclusion, endogenous ecSOD plays an important role in protection against endothelial dysfunction during aging.

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