Differential regulation of HLA-DR mRNAs and cell surface antigens by interferon.

Rosa, Frédéric; Hatat, D.; Abadie, A; Wallach, David; Revel, Michel; Fellous, Marc

doi:10.1002/j.1460-2075.1983.tb01628.x

Cited by 106 publications

(45 citation statements)

References 22 publications

(11 reference statements)

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“…The HLA class I mRNA was induced 2 -3 times more in y-IFN-treated cells than in a-IFN-treated cells (cf. [7]) 6-16 mRNA was not induced significantly by y-IFN (Fig. 3 b), providing an examplc of a mRNA induced specifically by a-IFN.…”

Section: Induction Qf Mrnas By Y-ifnmentioning

confidence: 72%

“…When the effects of a-and y-interferons were compared, the induced levels and kinetics were very similar for one mRNA (1-8) but were significantly different for the others. One mRNA (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) was induced more than 100-fold by a-interferon but not significantly by y-interferon. Parallel analysis of the level of c-myc mRNA showed it to decrease twofold in response to a-interferon, but to increase more than threefold in response to y-interferon, despite a more profound inhibition of cell growth by the latter.…”

mentioning

confidence: 99%

“…These include cDNAs corresponding to a 2-5A synthetase [20], a 56-kDa protein [21] and a number of HLA class I and I1 antigens (e.g. [7]) from human cells, and a 56-kDa protein [22] and the Mx protein [I 61, which is associated with resistance against influenza virus, from mouse cells. In our own laboratory, cDNAs for several mRNAs induced by human a-IFNs have been isolated and sequenced, including those for metallothionein (MTII) and an HLA class I antigen [17].…”

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confidence: 99%

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Differential regulation of interferon‐induced mRNAs and c‐myc mRNA by α‐ and γ‐interferons

Kelly¹,

Gilbert²,

Stark³

et al. 1985

European Journal of Biochemistry

108

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The extent and kinetics of induction have been determined for eight mRNAs induced by a-and y-interferons in HeLa cells. The mRNAs which code for a 2-5A synthetase, metallothionien 11, HLA class I antigen and five unknown proteins were induced 2-> 100-fold by a-interferons. In the continued presence of a-interferon some mRNAs were maintained at the induced levels until at least 40 h, whereas others were induced only transiently. When the effects of a-and y-interferons were compared, the induced levels and kinetics were very similar for one mRNA (1-8) but were significantly different for the others. One mRNA (6-16) was induced more than 100-fold by a-interferon but not significantly by y-interferon. Parallel analysis of the level of c-myc mRNA showed it to decrease twofold in response to a-interferon, but to increase more than threefold in response to y-interferon, despite a more profound inhibition of cell growth by the latter. There must, therefore, be differences in how the levels of different mRNAs are sustained by a-interferons and how a-and y-interferons regulate the levels of the same mRNAs. . When an IFN binds to its receptor there is an increase in both the rates of transcription and the steady-state levels of induced mRNAs [15, 17, 181. In contrast the levels of at least one mRNA, c-myc, is reduced in cells treated with p-IFN [19]. The mechanisms by which the different IFNs affect the intracellular levels of mRNA are not known and the roles played by most of the induced proteins in the antiviral response or growth regulation remain to be elucidated.Complementary DNA (cDNA) clones corresponding to several mRNAs induced by IFN in human and mouse cells have been isolated and characterised. These include cDNAs corresponding to a 2-5A synthetase [20], a 56-kDa protein [21] and a number of HLA class I and I1 antigens (e.g. [7]) from human cells, and a 56-kDa protein [22] and the Mx protein [I 61, which is associated with resistance against influenza virus, from mouse cells. In our own laboratory, cDNAs for several mRNAs induced by human a-IFNs have been isolated and sequenced, including those for metallothionein (MTII) and an HLA class I antigen [17]. In the present work,

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Section: Induction Qf Mrnas By Y-ifnmentioning

confidence: 72%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Differential regulation of interferon‐induced mRNAs and c‐myc mRNA by α‐ and γ‐interferons

Kelly¹,

Gilbert²,

Stark³

et al. 1985

European Journal of Biochemistry

108

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“…The two types of IFNs (␣␤ and ␥) bind to unique cell surface receptors, which induce the transcription of a number of distinct, but overlapping sets of genes (1)(2)(3). Among the genes that are inducible by both ␣␤ and ␥ IFNs are the MHC class I genes (1, 4 -7).…”

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confidence: 99%

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Snyder

Waring

Sheng

et al. 2001

The Journal of Immunology

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The expression of several MHC class I genes is up-regulated at the transcriptional level by IFN-γ. Posttranscriptional mechanisms also have been implicated, but not well characterized. To investigate the mechanism of IFN-γ stimulation of the human MHC class I gene HLA-A2, several human tumor cell lines were transfected with reporter gene constructs driven by the HLA-A2 promoter. We have previously shown that the extended 525-bp HLA-A2 promoter alone, which includes a 5′ IFN-stimulated response element consensus sequence, is not sufficient for IFN-γ response in either K562 or Jurkat cells. In the current study, stable transfection of a genomic HLA-A2 gene construct, containing both 5′- and 3′-flanking sequences, resulted in stimulation of the gene by IFN-γ. Nuclear run-on assays revealed that, unlike other class I genes, IFN-γ stimulation of HLA-A mRNA accumulation occurs almost entirely through posttranscriptional mechanisms. RNA stability assays showed that the effect is not mediated by alteration of the half-life of the HLA-A2 mRNA. Formation of the 3′ end was unaffected by IFN-γ treatment. Sequences that mediate the majority of IFN-γ induction of HLA-A2 mRNA reside in a 127-bp 3′-transcribed region of the gene. This region contains the terminal splice site, the usage of which is not affected by IFN-γ treatment. These results demonstrate a novel posttranscriptional mechanism of regulation of MHC class I genes by IFN-γ.

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“…[20][21][22][23] Indeed, our data showed that in vitro infection of AK7 cells with Ad.mIFN-g enhanced the expression of MHC antigens, more significantly class I antigens that are expressed at low levels by uninfected AK7 cells (Fig 2). Abundant CD4 + and CD8 + aggregates, which were not detected in PBS-and Ad.bgaltreated tumors, were present in Ad.mIFN-g-treated tumors of immunocompetent mice (Fig 7f-h).…”

Section: Discussionmentioning

confidence: 59%

Regression of AK7 malignant mesothelioma established in immunocompetent mice following intratumoral gene transfer of interferon gamma

et al. 2003

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Malignant mesothelioma (MM) is a lethal tumor linked with a prior exposure to asbestos in which limited progress has been made so far using conventional therapies. MM is an example of a ''nonimmunogenic'' tumor characterized by a fibrous stroma and an absence of infiltrating T lymphocytes. High levels of transforming growth factor-beta (TGF-b) produced by mesothelioma cells have been related to the immune tolerance towards the tumor. In order to evaluate the effect of local delivery of cytokines such as interferon gamma (IFN-g) by gene transfer, we characterized and used a murine model, AK7, which appeared very similar to human mesothelioma. AK7 cells expressed low levels of major histocompatibility class I and class II antigens and secreted high levels of latent TGF-b. The TGF-b pathway in AK7 cells is operative but inefficient because endogenous TGF-b is predominantly inactive. Treatment of pre-established AK7 tumors by direct intratumoral injection of an adenovirus vector expressing murine IFN-g, Ad.mIFN-g, led to significant tumor regression. Peripheral tumor infiltration by CD4+ and CD8+ T lymphocytes in the treated tumors appeared to be because of the induction of an immune response. Tumor relapse was observed, which could be due to local TGF-b secretion by remaining tumor cells.

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Differential regulation of HLA-DR mRNAs and cell surface antigens by interferon.

Cited by 106 publications

References 22 publications

Differential regulation of interferon‐induced mRNAs and c‐myc mRNA by α‐ and γ‐interferons

Differential regulation of interferon‐induced mRNAs and c‐myc mRNA by α‐ and γ‐interferons

A 3′-Transcribed Region of the HLA-A2 Gene Mediates Posttranscriptional Stimulation by IFN-γ

Regression of AK7 malignant mesothelioma established in immunocompetent mice following intratumoral gene transfer of interferon gamma

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