Regulation of gene expression by cytokines and virus in human cells lacking the type-I interferon locus.
A number of genes that are induced by type-I interferons are also activated by one or more other inducers, including double-stranded RNA, viruses, interferon-gamma, interleukin-1 and tumor necrosis factor. However, these inducers can also activate the expression of type-I interferons. Thus, the activation of type-I interferon-inducible genes by these other inducers could be direct, or a secondary consequence of the induction of interferon. To distinguish between these possibilities, we have used cell lines lacking all type-I interferon genes to study the direct effect of potential inducers on the expression of 14 interferon-inducible human genes. We show that double-stranded RNA, virus, interferon-gamma or tumor necrosis factor-alpha can act directly to induce specific subsets of type-I interferon-inducible genes in the absence of any possible type-I interferon involvement. The cis-acting element which confers inducibility by type-I interferon has been shown in some cases to confer inducibility by interferon-gamma, double-stranded RNA or virus as well. However, not all promoters containing such an element respond to both interferon and other inducers. Thus, the ability of a given gene to respond to different inducers most likely depends on the exact nature and specific combination of cis-acting elements present in its promoter.
Wathelet
M G
MG
Département de Biologie Moléculaire, Université Libre de Bruxelles, Belgium.
Berr
P M
PM
Huez
G A
GA
D000818:Animals; D015152:Blotting, Northern; D016207:Cytokines / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D007370:Interferon Type I / Q000235:genetics* / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology; D009522:Newcastle disease virus / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014709:Vero Cells; D014721:Vesicular stomatitis Indiana virus / Q000502:physiology; D018406:Virus Physiological Phenomena
D016207:Cytokines; D007370:Interferon Type I; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011070:Poly I-C