Concanavalin A-induced granulocyte-macrophage colony-stimulating factor production in a murine T-cell line is posttranscriptionally controlled.
Exp Hematol
; 20(2): 271-5, 1992 Feb.
Article
em En
| MEDLINE
| ID: mdl-1544398
ABSTRACT
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a hematopoietic growth factor (HGF) that regulates the proliferation and differentiation of cells of the myeloid lineage. It can be produced by a variety of cells. One of the major sources of GM-CSF is activated T cells, which transiently produce this HGF. We used the EL-4 thymoma cell line as a model system to address the molecular basis for GM-CSF regulation in T cells. Both concanavalin A (ConA) and the phorbol ester, 12-O-tetradecanoylphorbol 13-acetate (TPA) induce GM-CSF expression in EL-4 cells. However, the biological activity of GM-CSF in the supernatants of the TPA-stimulated cells was higher than that of ConA-stimulated cells. To elucidate this difference in biological activity levels, we examined how ConA regulates GM-CSF gene expression in EL-4 cells and compared it to the better-characterized regulation by TPA. Peak mRNA levels of GM-CSF occur 6 h after stimulation with either of these two agents. GM-CSF mRNA levels after ConA treatment are lower and decrease significantly after 10 h compared to TPA treatment, which causes much higher levels that persist for at least 24 h. Neither agent alters GM-CSF gene transcription. Actinomycin D chase experiments show that ConA increases the GM-CSF mRNA half-life from less than 30 to 90 min, whereas TPA prolongs it to greater than 3 h. These results indicate that GM-CSF mRNA induction by ConA (in common with TPA) is regulated predominantly via RNA stabilization and that the difference in prolongation of the mRNA half-life provides the primary explanation for the lower levels of GM-CSF mRNA induced by ConA compared to TPA.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Processamento Pós-Transcricional do RNA
/
Fator Estimulador de Colônias de Granulócitos e Macrófagos
/
Concanavalina A
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
1992
Tipo de documento:
Article