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The role of the NADPH oxidase complex, p38 MAPK, and Akt in regulating human monocyte/macrophage survival.
- Source :
-
American journal of respiratory cell and molecular biology [Am J Respir Cell Mol Biol] 2007 Jan; Vol. 36 (1), pp. 68-77. Date of Electronic Publication: 2006 Aug 24. - Publication Year :
- 2007
-
Abstract
- M-CSF induces PI 3-kinase activation, resulting in reactive oxygen species (ROS) production. Previously, we reported that ROS mediate macrophage colony-stimulating factor (M-CSF)-induced extracellular regulated kinase (Erk) activation and monocyte survival. In this work, we hypothesized that M-CSF-stimulated ROS products modulated Akt1 and p38 activation. Furthermore, we sought to clarify the source of these ROS and the role of ROS and Akt in monocyte/macrophage survival. Macrophages from p47(phox-/-) mice, lacking a key component of the NADPH oxidase complex required for ROS generation, had reduced cell survival and Akt1 and p38 mitogen-activated protein kinase (MAPK) phosphorylation compared with wild-type macrophages in response to M-CSF stimulation, but had no difference in M-CSF-stimulated Erk. To understand how ROS affected monocyte survival and signaling, we observed that NAC and DPI decreased cell survival and Akt1 and p38 MAPK phosphorylation. Using bone marrow-derived macrophages from mice expressing constitutively activated Akt1 (Myr-Akt1) or transfecting Myr-Akt1 constructs into human peripheral monocytes, we concluded that Akt is a positive regulator of monocyte survival. Moreover, the p38 MAPK inhibitor, SB203580, inhibited p38 activity and M-CSF-induced monocyte survival. These findings demonstrate that ROS generated from the NADPH oxidase complex contribute to monocyte/macrophage survival induced by M-CSF via regulation of Akt and p38 MAPK.
- Subjects :
- Animals
Bone Marrow Cells physiology
Cell Survival
Cells, Cultured
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases metabolism
Humans
Imidazoles pharmacology
Macrophage Colony-Stimulating Factor physiology
Macrophages physiology
Mice
Phosphorylation
Pyridines pharmacology
Reactive Oxygen Species metabolism
Signal Transduction
p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
Monocytes physiology
NADPH Oxidases metabolism
Proto-Oncogene Proteins c-akt metabolism
p38 Mitogen-Activated Protein Kinases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1044-1549
- Volume :
- 36
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- American journal of respiratory cell and molecular biology
- Publication Type :
- Academic Journal
- Accession number :
- 16931806
- Full Text :
- https://doi.org/10.1165/rcmb.2006-0165OC