J. Gogusev et al., REGULATION OF TNF-ALPHA AND IL-1 GENE-EXPRESSION DURING TPA-INDUCED DIFFERENTIATION OF MALIGNANT HISTIOCYTOSIS DEL CELL-LINE T(5-6) (Q35-P21), Anticancer research, 16(1), 1996, pp. 455-460
The production of TNF-alpha and IL-1 alpha and beta molecules has been
shown to be associated with the proliferation and activation of cells
of the monocyte/macrophage series the intermediate steps in the synth
esis of these molecules have been less investigated Unstimulated and T
PA stimulated DEL cells (a CD30-positive, t(5;6)(q35;p21) malignant hi
stiocytosis cell line) were used to study the expression of TNF-alpha
and IL-1 genes and to evaluate, by nuclear run-on assay and biological
measurements, the control of their transcription and the level of pro
tein production. To refine this analysis, the effects of cycloheximide
and actinomycin D were also evaluated in this investigation. Followin
g TPA stimulation, transcription of TNF-alpha (constitutively present)
increased threefold as early as 30 mins and stat-red decreasing by 24
h. Cycloheximide superinduced the expression of TNF-alpha mRNA and ac
cordingly, the release of its protein. By contrast, transcription of I
L-1 molecules appeared de novo and did not result in a biologically de
tectable protein. Measurements of RNA half life after actinomycin D in
dicated that TNF-alpha and IL-1 alpha mRNAs are not as stable as that
of IL-1 beta. These results indicate that, despite their common synerg
istic activity, the transcriptional and post-transcriptional mechanism
s regulating the synthesis of TNF-alpha and IL-1 alpha and IL-1 beta i
nvolve different pathways.