TY - JOUR
T1 - Insulin-like growth factor-I and the cytokines IL-3 and IL-4 promote survival of progenitor myeloid cells by different mechanisms
AU - Burgess, William
AU - Jesse, Katie
AU - Tang, Qinsong
AU - Broussard, Suzanne R.
AU - Dantzer, Robert
AU - Kelley, Keith W.
PY - 2003/2
Y1 - 2003/2
N2 - 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.
AB - 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.
KW - Akt
KW - Apoptosis
KW - Caspase-3
KW - Cytokines
KW - Hemopoiesis
KW - Hormones
UR - http://www.scopus.com/inward/record.url?scp=0037311258&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037311258&partnerID=8YFLogxK
U2 - 10.1016/S0165-5728(02)00443-5
DO - 10.1016/S0165-5728(02)00443-5
M3 - Article
C2 - 12576227
AN - SCOPUS:0037311258
SN - 0165-5728
VL - 135
SP - 82
EP - 90
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -