| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Animal Sciences, Faculty of Agricultural, Food, and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot, Israel; Departments of
Biological Regulation and
Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel; and
Eye Department, Kaplan Medical Center, Rehovot, Israel
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-
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- and of the metalloproteinases MMP-2 and MMP-9 from PEM. Disulfiram (DSF), an inhibitor of SOD-1, strongly inhibited the release of TNF-, 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- levels and 2-fold stronger delayed-type hypersensitivity reaction as compared with control nontransgenic mice. Conversely, oral administration of DSF lowered TNF- 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.
This article has been cited by other articles:
|
|
 |
|
  E. R. Tuller, C. T. Beavers, J. R. Lou, M. A. Ihnat, D. M. Benbrook, and W.-Q. Ding Docosahexaenoic Acid Inhibits Superoxide Dismutase 1 Gene Transcription in Human Cancer Cells: The Involvement of Peroxisome Proliferator-Activated Receptor {alpha} and Hypoxia-Inducible Factor-2{alpha} Signaling Mol. Pharmacol., September 1, 2009; 76(3): 588 - 595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Ishihara, K.-I. Tanaka, Y. Tasaka, T. Namba, J. Suzuki, T. Ishihara, S. Okamoto, T. Hibi, M. Takenaga, R. Igarashi, et al. Therapeutic Effect of Lecithinized Superoxide Dismutase against Colitis J. Pharmacol. Exp. Ther., January 1, 2009; 328(1): 152 - 164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Beers, J. S. Henkel, W. Zhao, J. Wang, and S. H. Appel CD4+ T cells support glial neuroprotection, slow disease progression, and modify glial morphology in an animal model of inherited ALS PNAS, October 7, 2008; 105(40): 15558 - 15563. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Rocic, C. Kolz, R. Reed, B. Potter, and W. M. Chilian Optimal reactive oxygen species concentration and p38 MAP kinase are required for coronary collateral growth Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2729 - H2736. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. MUKBEL, C. PATTEN JR., K. GIBSON, M. GHOSH, C. PETERSEN, and D. E. JONES MACROPHAGE KILLING OF LEISHMANIA AMAZONENSIS AMASTIGOTES REQUIRES BOTH NITRIC OXIDE AND SUPEROXIDE Am J Trop Med Hyg, April 1, 2007; 76(4): 669 - 675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. P. Bowler, M. Nicks, K. Tran, G. Tanner, L.-Y. Chang, S. K. Young, and G. S. Worthen Extracellular Superoxide Dismutase Attenuates Lipopolysaccharide-Induced Neutrophilic Inflammation Am. J. Respir. Cell Mol. Biol., October 1, 2004; 31(4): 432 - 439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Brar, C. Grigg, K. S. Wilson, W. D. Holder Jr., D. Dreau, C. Austin, M. Foster, A. J. Ghio, A. R. Whorton, G. W. Stowell, et al. Disulfiram inhibits activating transcription factor/cyclic AMP-responsive element binding protein and human melanoma growth in a metal-dependent manner in vitro, in mice and in a patient with metastatic disease Mol. Cancer Ther., September 1, 2004; 3(9): 1049 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Nguyen, T. D'Aigle, G. Gowing, J.-P. Julien, and S. Rivest Exacerbation of Motor Neuron Disease by Chronic Stimulation of Innate Immunity in a Mouse Model of Amyotrophic Lateral Sclerosis J. Neurosci., February 11, 2004; 24(6): 1340 - 1349. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
