Granulocyte-macrophage colony-stimulating factor, phorbol ester, and sodium butyrate induce the CD11c integrin gene promoter activity during myeloid cell differentiation.
Abstract
To analyze the activity of the CD11c promoter during myeloid differentiation without the limitations of transient expression systems, we have stably transfected the myeloid U937 cell line with the pCD11C361-Luc plasmid, in which the expression of the firefly luciferase cDNA is driven by the CD11c promoter region -361/+43, previously shown to confer myeloid specificity to reporter genes. The stable transfectants (U937-C361) retained the ability to differentiate in response to phorbol-ester (PMA), sodium butyrate (SB), granulocyte-macrophage colony-stimulating factor (GM-CSF), and other differentiating agents. U937-C361 differentiation correlated with increased cellular luciferase levels, showing the inducibility of the CD11c promoter during myeloid differentiation and establishing the U937-C361 cells as a suitable system for studying the myeloid differentiation-inducing capacity of cytokines, growth, factors, and other biological response modifiers. Unexpectedly, the inducibility of the CD11c gene promoter showed distinct kinetics and magnitude on the PMA-, SB-, GM-CSF-triggered differentiation. Moreover, SB synergized with either PMA or GM-CSF in enhancing both the CD11c promoter activity and the cell surface expression of p150,95 on differentiating U937 cells. Furthermore, we showed the existence of a c-Myb-binding site at -85, the importance of the -99/-61 region in the CD11c promoter inducibility during PMA- or SB-triggered differentiation, and the dependency of the GM-CSF and PMA responsiveness of the CD11c promoter on an intact AP-1-binding site located at -60. These results, together with the lack of functional effect of mutations disrupting the Sp1-and Myb-binding sites within the proximal region of the CD11c promoter, indicate that the myeloid differentiation pathways indicated by SB and phorbol esters (or GM-CSF) activate a distinct set of transcription factors and show that the myeloid differentiation-inducibility of the CD11c gene maps to the -99/-53 proximal region of the promoter.Citation
Blood, 86(10): 3715-3724Publisher
American Society of HematologyPubMed ID
7579338Additional Links
http://www.bloodjournal.org/cgi/reprint/86/10/3715Type
Journal articleLanguage
enISSN
0006-4971Collections
Related articles
- CD11c integrin gene promoter activity during myeloid differentiation.
- Authors: Córbi AL, Lopéz-Rodríguez C
- Issue date: 1997 May
- Multiple signals are required for function of the human granulocyte-macrophage colony-stimulating factor gene promoter in T cells.
- Authors: Jenkins F, Cockerill PN, Bohmann D, Shannon MF
- Issue date: 1995 Aug 1
- During differentiation of the monocytic cell line U937, Pur alpha mediates induction of the CD11c beta 2 integrin gene promoter.
- Authors: Shelley CS, Teodoridis JM, Park H, Farokhzad OC, Böttinger EP, Arnaout MA
- Issue date: 2002 Apr 15
- Granulocyte-colony stimulating factor, granulocyte-macrophage colony stimulating factor and interleukin 4 induce differentiation in the U-937 human monocytic leukemia cell line.
- Authors: Koss A, Lucero G, Koziner B
- Issue date: 1996 Jun
- AP-1 regulates the basal and developmentally induced transcription of the CD11c leukocyte integrin gene.
- Authors: López-Rodríguez C, Kluin-Nelemans HC, Corbí AL
- Issue date: 1996 May 15