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Induction of phospholipid hydroperoxide glutathione peroxidase in human polymorphonuclear neutrophils and HL60 cells stimulated with TNF-alpha.
- Source :
-
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2005 Nov 18; Vol. 337 (2), pp. 464-73. Date of Electronic Publication: 2005 Sep 21. - Publication Year :
- 2005
-
Abstract
- Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is characterized as an important enzyme for protecting cells from oxidative stress-induced apoptosis and regulating the production of leukotrienes and prostanoids in cells overexpressing PHGPx. We studied whether the expression level of PHGPx fluctuates in polymorphonuclear leukocytes (PMNs) which were exposed to reactive oxygen species (ROS) and inflammatory cytokines at an inflammation site. Human peripheral PMNs up-regulated the expression level of PHGPx following culture with TNF-alpha, but not with IL-1beta, IL-8, and GRO. The up-regulated PHGPx expression was also observed in neutrophil-like cells that differentiated from the human leukemia cell line HL60 only after stimulation with TNF-alpha. However, macrophage-like differentiated HL60 cells and other cell lines, A498, ECV304, HeLa, U937, and HEK293, showed no increase in the PHGPx expression. This up-regulation of PHGPx was inhibited by treatment with the anti-oxidants, pyrrolidine dithiocarbamate, and N-acetyl-L-cysteine, and by inhibitors of NFkappaB and Src kinases. The stimulation of neutrophil-like differentiated HL60 cells with TNF-alpha induced activation of NFkappaB and c-Src kinase, and the activation was attenuated by treatment with the anti-oxidants. Up-regulation in neutrophil-like HL60 cells was also observed following exposure to H(2)O(2). These results indicate that activation of NFkappaB and/or Src kinases through ROS signaling may be involved in the up-regulation of the PHGPx in human PMNs stimulated by TNF-alpha.
- Subjects :
- Antioxidants pharmacology
Cells, Cultured
Chemokine CXCL1
Chemokines, CXC pharmacology
Cytokines metabolism
Gene Expression
HL-60 Cells
Humans
Inflammation Mediators metabolism
Intercellular Signaling Peptides and Proteins pharmacology
Interleukin-1 pharmacology
Interleukin-8 pharmacology
Neutrophils metabolism
Phospholipid Hydroperoxide Glutathione Peroxidase
Reactive Oxygen Species metabolism
Up-Regulation
Glutathione Peroxidase metabolism
Neutrophils drug effects
Tumor Necrosis Factor-alpha pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0006-291X
- Volume :
- 337
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical and biophysical research communications
- Publication Type :
- Academic Journal
- Accession number :
- 16223606
- Full Text :
- https://doi.org/10.1016/j.bbrc.2005.09.076