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NF-kappa B Transcription Factors Are Involved in Normal Erythropoiesis

Min-Ying Zhang, Shao-Cong Sun, Laurie Bell, and Barbara A. Miller

From the Departments of Pediatrics and Microbiology and Immunology, The Pennsylvania State University College of Medicine, Milton S. Hershey Medical Center, Hershey, PA.

NF-kappa B/Rel designates a widely distributed family of transcription factors involved in immune and acute phase responses. Here, the expression and function of NF-kappa B factors in erythroid proliferation and differentiation were explored. In an erythroleukemia cell line, TF-1, high levels of p105/p50, p100/p52, p65, and Ikappa Balpha were detected 24 hours after growth factor deprivation. In response to granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulation, significant induction of p52 expression was observed. GM-CSF also induced nuclear translocation of both p52 and p65. No induction of NF-kappa B factors was observed with erythropoietin stimulation of TF-1 cells. Overexpression of p52 and p65 in TF-1 cells by transient transfection resulted in significant induction of a kappa B-TATA-luciferase reporter plasmid, showing that these factors are functional in vivo in erythroid cells. To determine whether NF-kappa B factors may play a role in normal erythropoiesis, levels of these factors were determined in burst-forming unit-erythroid (BFU-E)-derived cells at different stages of differentiation. The NF-kappa B factors p105/p50, p100/p52, and p65 were highly expressed in early BFU-E-derived precursors, which are rapidly proliferating, and declined during maturation. Furthermore, nuclear levels of NF-kappa B factors p50, p52, and p65 were higher in less mature precursors (day 10 BFU-E-derived cells) compared with more differentiated (day 14) erythroblasts. In nuclear extracts from day 10 BFU-E-derived 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 be among the kappa B-containing genes regulated by NF-kappa B factors in normal erythroid cells. Taken together, these data show that NF-kappa B factors are modulated by GM-CSF and suggest they function to regulate specific kappa B containing genes involved in erythropoiesis.

Blood, Vol. 91 No. 11 (June 1), 1998: pp. 4136-4144
© 1998 by The American Society of Hematology.


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