TRANSCRIPTIONAL REGULATION OF THE INTERFERON-BETA-2/B CELL-DIFFERENTIATION FACTOR BSF-2/HEPATOCYTE-STIMULATING FACTOR GENE IN HUMAN-FIBROBLASTS BY OTHER CYTOKINES

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  • 1 February 1988
    • journal article
    • research article
    • Vol. 140  (3) , 974-977
Abstract
Levels of mRNA for IFN-.beta.2/B cell differentiation factor2/hepatocyte-stimulating factor (IFN-.beta.2) in confluent quiescent cultures of human diploid fibroblasts (FS-4 strain) are enhanced by TNF, IL-1.alpha. and .beta., platelet-derived growth factor (PDGF) and IFN-.beta.1. Of these cytokines, IL-1.alpha. and .beta. cause a particularly strong increase in the accumulation of IFN-.beta.2 mRNA in fibroblasts. We have evaluated whether the IFN-.beta.2 gene is regulated at the transcriptional level by using nuclear run-on transcription assays. We observed that the IFN-.beta.2 gene is transcribed at a low level in uninduced FS-4 cells and that this transcriptional activity is increased 2- to 3-fold in cycloheximide-treated cells, 20- to 35-fold in IL-1.alpha.-treated cells, and 5- to 15-fold in TNF-treated cells. PDGF and IFN-.beta.1 enhance transcription across the IFN-.beta.2 gene 2- to 3-fold. The enhancing effect of IL-1.alpha. on IFN-.beta.2 gene transcription, but not that of TNF, PDGF, or IFN-.beta.1, is inhibited by cycloheximide, suggesting that newly-synthesized protein is involved in the increase in IFN-.beta.2 transcription in response to IL-1.alpha. but not in the response to the other stimuli. Furthermore, the enhancement of IFN-.beta.2 transcription is sustained for up to 14 h after IL-1.alpha. induction but is transient and declines to base line levels within 6 h after TNF addition. These observations suggest that there are important differences in the mechanisms by which IL-1.alpha. and TNF increase IFN-.beta.2 gene transcription in fibroblasts.