Transcriptional modulation of human T-cell growth factor gene by phorbol ester and interleukin 1.

T-cell growth factor (TCGF) is a protein that is required for the continuous proliferation of activated normal T lymphocytes. It is produced by a subset of T lymphocytes upon appropriate stimulation. A human leukemic T-cell line (Jurkat) can be induced with the lectin phytohemagglutinin and the phorbol ester tetradecanoylphorbolacetate (TPA) to produce T-cell growth factor. This production was enhanced by including the lymphokine interleukin 1 in the induction medium. Interleukin 1 alone did not substantially increase T-cell growth factor production by cells treated only with phytohemagglutinin. These effects were preceded by and correlated with the induction of T-cell growth factor mRNA. Northern blot experiments with cloned TCGF DNA as a probe showed that TCGF mRNA was induced rapidly in cells treated with TPA and phytohemagglutinin, and this induction was augmented by interleukin 1. Thus, the production of T-cell growth factor was regulated at the level of its mRNA. Nuclear transcription experiments suggested that the TCGF gene was more actively transcribed in cells treated with TPA and phytohemagglutinin than in cells treated with phytohemagglutinin alone. The transcription of the TCGF gene was further increased when interleukin 1 was included along with TPA and phytohemagglutinin. When continued synthesis of RNA in induced cells was blocked with actinomycin D and cells were subsequently cultured in the presence or absence of inducing agents, the steady-state levels of TCGF mRNA declined in all cultures. This decline was roughly equivalent in cells incubated without the inducers and those incubated with phytohemagglutinin.(ABSTRACT TRUNCATED AT 250 WORDS)