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Antiapoptotic effect of granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and cyclic AMP on human neutrophils: protein synthesis-dependent and protein synthesis-independent mechanisms and the role of the Janus kinase-STAT pathway
- Source :
- International journal of hematology. 77(1)
- Publication Year :
- 2003
-
Abstract
- Spontaneous neutrophil apoptosis during culture was delayed by granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), or dibutyryl-cyclic adenosine monophosphate (cAMP), whereas apoptosis was accelerated by cycloheximide or actinomycin D. G-CSF-mediated antiapoptosis was completely abolished by cycloheximide or actinomycin D, whereas GM-CSF-mediated antiapoptosis was not completely abolished by these inhibitors. Antiapoptosis induced by dibutyryl-cAMP was highly resistant to cycloheximide, and that induced by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone was unaffected by cycloheximide. G-CSF- and GM-CSF-mediated antiapoptosis and phosphorylation of signal transducer and activator of transcription 3 (STAT3) and STAT5 were inhibited by AG490, an inhibitor of Janus kinase. The level of Mcl-1 protein was not associated with neutrophil apoptosis. The results suggest that (a) neutrophil survival in the resting state is primarily regulated by the constitutive synthesis of antiapoptotic proteins; (b) the prevention of spontaneous apoptosis is mediated through the protein synthesis-dependent and/or protein synthesis-independent mechanisms according to the stimuli used; and (c) the Janus kinase-STAT pathway is involved in G-CSF- and GM-CSF-mediated antiapoptosis.
- Subjects :
- Adenosine monophosphate
STAT3 Transcription Factor
Transcription, Genetic
Neutrophils
Apoptosis
Biology
Cycloheximide
Granulocyte
chemistry.chemical_compound
Proto-Oncogene Proteins
Granulocyte Colony-Stimulating Factor
medicine
STAT5 Transcription Factor
Humans
Enzyme Inhibitors
Phosphorylation
STAT3
STAT5
JAK-STAT signaling pathway
Granulocyte-Macrophage Colony-Stimulating Factor
Hematology
Janus Kinase 2
Protein-Tyrosine Kinases
Milk Proteins
Molecular biology
DNA-Binding Proteins
medicine.anatomical_structure
chemistry
Bucladesine
Protein Biosynthesis
STAT protein
biology.protein
Trans-Activators
Janus kinase
Signal Transduction
Subjects
Details
- ISSN :
- 09255710
- Volume :
- 77
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- International journal of hematology
- Accession number :
- edsair.doi.dedup.....61bbfa74b26111fa9d9d8f1671c24d49