Human interleukin-3 mRNA accumulation is controlled at both the transcriptional and posttranscriptional level.
Interleukin-3 (IL-3) is a hematopoietic growth factor that regulates the differentiation of multilineage and committed progenitor cells and the functions of some mature blood cells. The expression of human IL-3 appears to be restricted to stimulated T lymphocytes. We have investigated the kinetics and mechanisms involved in the induction of IL-3 expression in the human T lymphocytic tumor cell line Jurkat. We show that accumulation of IL-3 mRNA is controlled at both the transcriptional and posttranscriptional level. Transcription of the IL-3 gene in these cells appears to be constitutive but no IL-3 mRNA was detected in unstimulated cells, indicating that in resting cells IL-3 mRNA is highly unstable. Treatment with phytohemagglutinin (PHA) induced a small and transient increase in the IL-3 gene transcription rate and led to the production of detectable levels of IL-3 mRNA and protein. Optimal induction of IL-3 expression required a second stimulus. Costimulation of Jurkat cells with both phorbol myristate acetate and PHA caused both a transient increase in IL-3 gene transcription, which is dependent on new protein synthesis, and also a transient increase in mRNA stability.
Ryan
G R
GR
Institute of Medical and Veterinary Science, Adelaide, South Australia.
Milton
S E
SE
Lopez
A F
AF
Bardy
P G
PG
Vadas
M A
MA
Shannon
M F
MF
D002460:Cell Line; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007377:Interleukin-3 / Q000235:genetics* / Q000378:metabolism; D016399:Lymphoma, T-Cell / Q000378:metabolism / Q000473:pathology; D010835:Phytohemagglutinins / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*
D007377:Interleukin-3; D010835:Phytohemagglutinins; D012333:RNA, Messenger; D013755:Tetradecanoylphorbol Acetate