The colony-stimulating factors induce expression of insulin-like growth factor-I messenger ribonucleic acid during hematopoiesis.
Murine bone marrow cells cultured in the presence of colony-stimulating factor-1 (CSF-1) showed coordinate induction of insulin-like growth factor-I (IGF-I) messenger RNA (mRNA) during the differentiation process, and these transcripts increased approximately 50- to 75-fold over the virtually negligible levels measured in freshly isolated bone marrow. In contrast, transcripts for the IGF-I receptor were evident in freshly isolated rat bone marrow cells and showed a 50% down-regulation during differentiation. Addition of a variety of single lineage and multilineage CSFs, including CSF-1, interleukin-3, granulocyte-macrophage-CSF, and granulocyte-CSF to mouse bone marrow cultures revealed that induction of IGF-I mRNA is a universal feature of differentiation with these CSFs, although IGF-I transcripts are at least 10- to 20-fold higher in CSF-1- and interleukin-3-differentiated lineages than in other cultures. The IGF-I induced by CSF-1 was biologically active because a natural ligand of IGF-I, IGF-binding protein-3, caused significant down-regulation of cellular proliferation, and this could be reversed by the addition of exogenous IGF-I. In addition, whereas IGF-I mRNA could be detected in resident peritoneal macrophages, these transcripts were increased 6-fold after a local injection of thioglycollate, a stimulus that induces macrophage proliferation and differentiation in vivo. These results show that CSFs induce expression of the growth factor IGF-I during differentiation of hematopoietic cells into multiple myeloid lineages and that this endogenously produced IGF-I is also a growth factor for hematopoietic cells. The induction of IGF-I mRNA during hematopoiesis should provide a new approach to understanding the expression of this gene during development and differentiation.
Arkins
S
S
Department of Animal Sciences, University of Illinois, Urbana 61801.
Rebeiz
N
N
Brunke-Reese
D L
DL
Minshall
C
C
Kelley
K W
KW
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D001854:Bone Marrow Cells; D002352:Carrier Proteins / Q000494:pharmacology; D002460:Cell Line; D003115:Colony-Stimulating Factors / Q000494:pharmacology*; D004247:DNA / Q000037:antagonists & inhibitors; D005260:Female; D006410:Hematopoiesis / Q000187:drug effects / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008264:Macrophages / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000378:metabolism*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D003115:Colony-Stimulating Factors; D018969:Insulin-Like Growth Factor Binding Proteins; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D004247:DNA