NP-KAPPA-B TRANSCRIPTION FACTORS ARE INVOLVED IN NORMAL ERYTHROPOIESIS

NF-kappa B/Rel designates a widely distributed family of transcription factors involved in immune and acute phase responses. Here, the expre ssion and function of NF-kappa B factors in erythroid proliferation an d differentiation were explored. In an erythroleukemia cell line, TF-1 , high levels of p105/p50, p100/p52, p65, and I kappa B alpha were det ected 24 hours after growth factor deprivation. In response to granulo cyte-macrophage colony-stimulating factor (GM-CSF) stimulation, signif icant induction of p52 expression was observed. GM-CSF also induced nu clear translocation of both p52 and p65. No induction of NF-kappa B fa ctors was observed with erythropoietin stimulation of TF-1 cells. Over expression of p52 and p65 in TF-1 cells by transient transfection resu lted in significant induction of a kappa B-TATA-luciferase reporter pl asmid, showing that these factors are functional in vivo in erythroid cells. To determine whether NF-kappa B factors may play a role in norm al erythropoiesis, levels of these factors were determined in burst-fo rming unit-erythroid (BFU-E)-derived cells at different stages of diff erentiation. The NF-kappa B factors p105/p50, p100/p52, and p65 were h ighly expressed in early BFU-E-derived precursors, which are rapidly p roliferating, and declined during maturation. Furthermore, nuclear lev els of NF-kappa B factors p50, p52, and p65 were higher in less mature precursors (day 10 BFU-E-derived cells) compared with more differenti ated (day 14) erythroblasts. In nuclear extracts from day 10 BFU-E-der ived cells, p50, p52; and p65 were able to form complexes, which bound to kappa B sites in the promoters of both the c-myb and c-myc genes, suggesting that c-myb and c-myc may he among the kappa B-containing ge nes regulated by NF-kappa B factors in normal erythroid cells. Taken t ogether, these data show that NF-kappa B factors are modulated by GM-C SF and suggest they function to regulate specific kappa B containing g enes involved in erythropoiesis. (C) 1998 by The American Society of H ematology.