Constitutive Expression of a Murine Interferon Alpha Gene in Hamster Cells and Characterization of Its Protein Product

Ec, Zwarthoff; Ij, Bosveld; Wp, Vonk; Trapman, Jan

doi:10.1099/0022-1317-66-4-685

Cited by 15 publications

(9 citation statements)

References 20 publications

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“…Preliminary data show that all three genes code for a protein with antiviral properties (data not shown). The protein product of gene 1OEF has already been studied in detail (33).…”

Section: Structure Of the Hu Ifn-a Genesmentioning

confidence: 99%

Organization, structure and expression of murine interferon alpha genes

1985

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Using a human interferon-alpha probe we have isolated recombinant phages containing murine interferon-alpha (Mu IFN-alpha) genes from a genomic library. One of these phages contained two complete Mu IFN-alpha genes and part of a third gene. The insert of a second phage held two IFN genes. This indicates that the Mu IFN-alpha genes are clustered in the genome as is the case for the analogous human genes. The nucleotide sequences of these 5 genes were determined. They show that the genes are all different, albeit highly homologous. The deduced amino acid sequences show that four of the five genes contain a putative glycosylation site. Three genes were transiently expressed in COS cells and they gave rise to protein products showing antiviral properties. The expression of the five Mu IFN-alpha genes and the Mu IFN-beta gene was studied in virus-induced mouse L cells. The individual mRNAs were visualized in a nuclease S1 experiment, using a specific probe for each gene. In RNA preparations from induced cells mRNAs for each of the five alpha genes and the beta gene were present. However, substantial differences in the amounts of the individual mRNAs were observed.

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“…Preliminary data show that all three genes code for a protein with antiviral properties (data not shown). The protein product of gene 1OEF has already been studied in detail (33).…”

Section: Structure Of the Hu Ifn-a Genesmentioning

confidence: 99%

Organization, structure and expression of murine interferon alpha genes

1985

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“…(O) control mice; (") anti-IFN-.y antibody treatment (F3 ascites, 0.1 ml i.p. )24 h before the preparatory LPS dose .…”

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confidence: 99%

Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice.

Heremans

Damme

Dillen

et al. 1990

The Journal of Experimental Medicine

201

119

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The involvement of cytokines in the pathogenesis of a generalized, Shwartzman-like lethal inflammatory response to bacterial lipopolysaccharides (LPS) was studied by testing the ability of cytokines or neutralizing anticytokine antibodies to modify the course of the syndrome. The reaction was elicitable in non-SPF NMRI mice by two consecutive injections of S. marcescens LPS: a first injection in the footpad, followed after 24 h by an intravenous dose; the size and route of the preparatory LPS dose were found to be critical. Treatment with mAbs against IFN-gamma was found to completely prevent the reaction. Treatment with IFN-gamma on the other hand, rendered the mice more sensitive to elicitation of the reaction. In contrast, systemic administration of IFN-alpha/beta exerted a desensitizing effect. The role of endogenous cytokines in the pathogenesis of this generalized Shwartzman reaction was also documented by a study of the cytokine levels in the serum of the mice. In comparisons between mice given lethal and nonlethal induction schedules, a good correlation was found between mortality rates and height of IFN or TNF levels, but no correlation was seen with IL-6 levels. Also, in mice that were protected by anti-IFN-gamma antibody, serum IFN and TNF were undetectable, whereas IL-6 levels were as high as in unprotected mice. These data provide evidence that among the cytokines that govern the inflammatory response to LPS, endogenous IFN-gamma occupies a key position. These findings therefore also open perspectives for clinical application of IFN-gamma antagonists.

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“…3A, B,C, lanes 8, 9,13,14). This is the case for both a 4 (15, 61) and for a 6 producers (28,106). In contrast, the ISG 54 transcript was undetectable or present at a very low level in producer cells (Fig.…”

Section: -mentioning

confidence: 74%

“…here for the a6 producer [28]. Interestingly, the a 1 protein also displays high antiviral activity on hamster cells [ 6 ] .…”

Section: Discussionmentioning

confidence: 93%

“…The IFN produced by these cell lines is very well suited for further characterization. Earlier, the present authors and others described the application of CHO cells for production of 7IFNs from different species [22-241, of human (Hu) IFN-a [25] and -6 [26,271 and Mu IFN-a1 [28]. In most of these studies, except for the amount of IFN produced, little attention has been given to other properties of the producer cells.…”

Section: Discussionmentioning

confidence: 99%

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Interferon‐α‐(IFN) producing CHO cell lines are resistant to the antiproliferative activity of IFN: A correlation with gene expression

Heuvel

Govaert-Siemerink

Bosveld

et al. 1988

J of Cellular Biochemistry

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CHO cell lines that constitutively produce the murine interferon-alpha (IFN-alpha) subspecies alpha 4 and alpha 6 were constructed. The producer cell lines were protected against viral (vesicular stomatitis virus) infection by the IFN species secreted, but were resistant to the growth inhibitory activity of the IFN species. As compared with alpha 4, the alpha 6 protein displayed a high antiproliferative activity when added to normal CHO cells, which correlates completely with the high antiviral activity of alpha 6 on these cells. Three messenger ribonucleic acid (mRNA) species, which are normally induced in CHO cells by IFN treatment (1-8, 2-5A synthetase, and ISG 15) were constitutively present in CHO producer cell lines. The level of another mRNA (ISG 54), however, was very low in the producer cells as compared with its expression in short-term IFN-treated cells. These data indicate that 1-8, 2-5A synthetase and ISG 15 are not involved in the antigrowth activity of IFN in this system, but rather suggest a function of ISG 54 in this respect.

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Constitutive Expression of a Murine Interferon Alpha Gene in Hamster Cells and Characterization of Its Protein Product

Cited by 15 publications

References 20 publications

Organization, structure and expression of murine interferon alpha genes

Organization, structure and expression of murine interferon alpha genes

Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice.

Interferon‐α‐(IFN) producing CHO cell lines are resistant to the antiproliferative activity of IFN: A correlation with gene expression

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