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Activated macrophage survival is coordinated by TAK1 binding proteins
- Source :
- PLoS ONE, Vol 9, Iss 4, p e94982 (2014), PLoS ONE
- Publication Year :
- 2014
- Publisher :
- Public Library of Science (PLoS), 2014.
-
Abstract
- Macrophages play diverse roles in tissue homeostasis and immunity, and canonically activated macrophages are critically associated with acute inflammatory responses. It is known that activated macrophages undergo cell death after transient activation in some settings, and the viability of macrophages impacts on inflammatory status. Here we report that TGFβ- activated kinase (TAK1) activators, TAK1-binding protein 1 (TAB1) and TAK1-binding protein 2 (TAB2), are critical molecules in the regulation of activated macrophage survival. While deletion of Tak1 induced cell death in bone marrow derived macrophages even without activation, Tab1 or Tab2 deletion alone did not profoundly affect survival of naive macrophages. However, in lipopolysaccharide (LPS)-activated macrophages, even single deletion of Tab1 or Tab2 resulted in macrophage death with both necrotic and apoptotic features. We show that TAB1 and TAB2 were redundantly involved in LPS-induced TAK1 activation in macrophages. These results demonstrate that TAK1 activity is the key to activated macrophage survival. Finally, in an in vivo setting, Tab1 deficiency impaired increase of peritoneal macrophages upon LPS challenge, suggesting that TAK1 complex regulation of macrophages may participate in in vivo macrophage homeostasis. Our results demonstrate that TAB1 and TAB2 are required for activated macrophages, making TAB1 and TAB2 effective targets to control inflammation by modulating macrophage survival.
- Subjects :
- Lipopolysaccharides
Lipopolysaccharide
Macrophage-activating factor
Gene Expression
lcsh:Medicine
Monocytes
chemistry.chemical_compound
White Blood Cells
Mice
Cell Signaling
Animal Cells
Molecular Cell Biology
Macrophage
Macrophage homeostasis
lcsh:Science
Macrophage inflammatory protein
Tissue homeostasis
Cellular Stress Responses
Mice, Knockout
Multidisciplinary
Cell Death
Protein Kinase Signaling Cascade
GTPase-Activating Proteins
Animal Models
MAP Kinase Kinase Kinases
Signaling Cascades
Cell biology
Cell Processes
medicine.symptom
Cellular Types
Research Article
Signal Transduction
Macrophage colony-stimulating factor
Cell Survival
Immune Cells
Immunology
Inflammation
Mouse Models
Biology
Research and Analysis Methods
Model Organisms
medicine
Genetics
Animals
Adaptor Proteins, Signal Transducing
Blood Cells
Macrophages
lcsh:R
Biology and Life Sciences
Cell Biology
Macrophage Activation
chemistry
lcsh:Q
Cytometry
Gene Deletion
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 9
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....5a67455233558bd108a7f0c9a23f689b