Insulin-like growth factor-I and the cytokines IL-3 and IL-4 promote survival of progenitor myeloid cells by different mechanisms

Hormones, such as insulin-like growth factor-I (IGF-I), and cytokines, like IL-3 and IL-4, promote survival of progenitor myeloid cells. Here we demonstrate that IGF-I, IL-3 and IL-4 all significantly block activation of caspase-3 in promyeloid cells following growth factor deprivation. However, onl...

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Bibliographic Details
Published in:Journal of neuroimmunology 2003-02, Vol.135 (1), p.82-90
Main Authors: Burgess, William, Jesse, Katie, Tang, Qinsong, Broussard, Suzanne R, Dantzer, Robert, Kelley, Keith W
Format: Article
Language:English
Subjects:
Akt
Androstadienes - pharmacology
Animals
Apoptosis
Apoptosis - drug effects
Caspase 3
Caspase Inhibitors
Cell Survival - drug effects
Cells, Cultured
Chromones - pharmacology
Cytokines
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - physiology
Hemopoiesis
Hormones
Insulin-Like Growth Factor I - pharmacology
Interleukin-3 - pharmacology
Interleukin-4 - pharmacology
Life Sciences
Mice
Morpholines - pharmacology
Phosphatidylinositol 3-Kinases - physiology
Phosphorylation
Protein-Serine-Threonine Kinases
Proto-Oncogene Proteins - biosynthesis
Proto-Oncogene Proteins c-akt
Serine - metabolism
Signal Transduction
Sirolimus - pharmacology
Wortmannin
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Summary:Hormones, such as insulin-like growth factor-I (IGF-I), and cytokines, like IL-3 and IL-4, promote survival of progenitor myeloid cells. Here we demonstrate that IGF-I, IL-3 and IL-4 all significantly block activation of caspase-3 in promyeloid cells following growth factor deprivation. However, only IL-3 and IGF-I increase enzymatic activity and phosphorylation of the survival-promoting kinase Akt. IGF-I fails to reduce caspase-3 activity and cell death in the presence of the PI 3-kinase inhibitors, wortmannin and LY294002, whereas these blockers do not affect the ability of IL-3 to maintain cell survival. IL-4 inhibits caspase-3 activity and promotes promyeloid cell survival by a substrate for PI 3-kinase that is not Akt. These data establish that IGF-I inhibits activation of caspase-3 and promotes promyeloid cell survival through a PI 3-kinase-dependent pathway, whereas IL-3 does not. It therefore appears that signal transduction pathways for all three receptors converge upstream of caspase-3 to prevent apoptosis of progenitor myeloid cells, but their receptors differ in the intracellular substrates that are used to promote cell survival.
ISSN:0165-5728
1872-8421
DOI:10.1016/S0165-5728(02)00443-5