The Cellular Effects of Interferon

Taylor, Jerry; Sabran, J L; Grossberg, Sidney E.

doi:10.1007/978-3-642-69178-2_9

Cited by 27 publications

(19 citation statements)

References 154 publications

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“…One of these effects is the pronounced growth inhibition of cells in culture (for a review see Taylor et al, 1984). This effect of IFN has been known for several years, but the molecular mechanisms by which IFN inhibits cell division are not understood.…”

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confidence: 99%

Treatment of lymphoblastoid cells with interferon decreases insulin binding

Faltynek¹,

McCandless²,

Baglioni³

1984

Journal Cellular Physiology

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Lymphoblastoid Daudi cells, which are highly sensitive to growth inhibition by interferon (IFN), can be grown in a defined serum-free medium containing insulin, transferrin, and albumin as the only proteins. We examined whether the growth inhibition by IFN could be in part due to a change in receptors for insulin or transferrin. Cells treated for at least 2 days with 100 units/ml of IFN-alpha 2 bound less 125I-insulin and after 3 days of treatment this binding was reduced by more than 50%. No change in the binding of 125I-transferrin was observed. Treatment with IFN of Raji cells, which are resistant to growth inhibition by IFN, resulted in a similar decrease in 125I-insulin binding. Growth inhibition of Daudi cells by serum deprivation had no effect on 125I-insulin binding. Therefore, the IFN-induced loss of insulin binding sites is not a consequence of growth inhibition.

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confidence: 99%

Treatment of lymphoblastoid cells with interferon decreases insulin binding

Faltynek¹,

McCandless²,

Baglioni³

1984

Journal Cellular Physiology

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“…The multiple effects of interferons (IFNs) on the phenotype of vertebrate cells include the establishment of antiviral resistance, reduction in the rate of cell proliferation, and inhibition or stimulation of the expression of many differentiated cellular functions (1,2). The primary actions of IFNs to achieve these very different effects remain uncertain, as are the loci of such actions.…”

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confidence: 99%

Murine interferon-beta receptor-mediated endocytosis and nuclear membrane binding.

Kushnaryov¹,

MacDonald²,

Sedmak³

et al. 1985

Proc. Natl. Acad. Sci. U.S.A.

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Radioiodinated mouse interferon-fl (125I-MuIFN-j3) bound with high affinity (Kd = 9.8 X 10-10 M) to plasma membrane of L929 murine fibroblasts (4-6 x 103 receptor sites per cell). The binding was saturable and inhibited by a 100-fold excess of unlabeled but not by excess mouse IFN-y (MuIFN-y). MuIFN-P bound at 40C was very rapidly internalized upon warming of the cells to 370C (t /2 = 1.5 min). Indirect immunoferritin labeling indicated that MuIFNfi was initially located in coated pits and subsequently internalized by receptor-mediated endocytosis. Isolated L929 cell nuclei bound 125I-MuIFN-fl with a 7-fold higher affinity (Kd = 1.4 x 10-10 M) and higher receptor density (about 104 per nucleus) than that for the plasma membrane. Binding to the nuclear membrane was inhibited by a 100-fold excess of unlabeled The multiple effects of interferons (IFNs) on the phenotype of vertebrate cells include the establishment of antiviral resistance, reduction in the rate of cell proliferation, and inhibition or stimulation of the expression of many differentiated cellular functions (1, 2). The primary actions of IFNs to achieve these very different effects remain uncertain, as are the loci of such actions. The first step in the action of IFN is its binding to a specific plasma membrane protein receptor (3-9) located in coated pits (4,8), which are specialized cell membrane formations involved in a highly selective and efficient mechanism of receptor-mediated endocytosis of ligands, such as hormones, serum lipoproteins, antibodies, toxins, and viruses (10, 11). Following binding, IFN can be internalized (3,7,8,12), but subsequent steps in its processing are unclear.Treatment with IFNs at physiological temperatures stimulates the synthesis of many polypeptides (13). Although some enzymes are induced or activated that are important in the inhibition of translation of viral proteins (14, 15), the effects on host cell synthetic activities remain less clear. If IFNs act only at the plasma membrane, second messenger(s) (16,17) or transmembrane signaling must be postulated to mediate such effects. However, if binding can be demonstrated on intracellular structures, such as nuclei, it is possible that IFN molecules can directly affect the functions of target organelles. Certain hormones, such as insulin or steroids (18)(19)(20), epidermal growth factor (21), and polyribonucleotides (22), have been shown to bind to the nuclear membrane, and some exert nuclear effects. In the present study we show by radiolabeling and immunocytochemical techniques that mouse IFN-/3 (MuIFN-03) is very rapidly internalized by the mechanism of receptor-mediated endocytosis and that MuIFN-f3 binds to isolated nuclei of mouse fibroblasts: not only are the nuclear membrane receptors of higher affinity than those on the plasma membrane, but they are also present in greater density.MATERIALS AND METHODS Cells. Mouse L929 fibroblasts were grown in suspension as described (4). After 3 days at 36WC, the cells were centrifuged, washed three times with E...

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“…Interferons were initially described for their antiviral activity [2]. In addition, other properties have been attributed to IFNs, such as cell growth inhibition and the modulation of differentiated function [for reviews see 1, [3][4][5]. The antiproliferative effects of IFNs on a wide variety of human tumor cell lines [6,7], mouse model systems [8][9][10] and clinical trials [11][12][13][14][15][16] have been well described.…”

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confidence: 99%

Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations

Dick

Hubbell

1987

J Neuro-Oncol

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The antiproliferative effects of human interferons (IFNs) and double-stranded RNAs (dsRNAs) were studied in five human glioma cell lines. Dose response curves were generated over a 72 hour treatment period. The concentration of interferon or double-stranded RNA necessary to produce a 50% antiproliferative response (GI50) was calculated by linear regression analysis. Two cell lines were more sensitive to IFN-beta than to IFN-alpha, one cell line was more sensitive to IFN-alpha than to IFN-beta and two cell lines had approximately equal sensitivities to both interferons. All cell lines showed some sensitivity to either IFN-alpha or IFN-beta. IFN-gamma had no antiproliferative effect on any of the cell lines. In addition, only one of the cell lines displayed sensitivity to dsRNA, in which the response to poly(I).poly(C) was greater than that to a mismatched analogue of poly(I).poly(C), r(I)n.r(C12,U)n (Ampligen). There was no correlation between the sensitivities to type I IFNs (alpha and beta), type II IFN (gamma) or the dsRNAs. The antiproliferative effect of combinations of IFNs, or IFNs and Ampligen, was studied in one of the cell lines. A significant synergistic antitumor effect was seen with all of the IFN/Ampligen combinations (p less than 0.02), including IFN-gamma/Ampligen, even though these cells were resistant to IFN-gamma alone. Synergy was also seen in the IFN-alpha/IFN-gamma (p less than 0.02) and IFN-beta/IFN-gamma (p less than 0.05) combinations. The IFN-alpha/IFN-beta combination gave an additive antitumor effect. These results indicate that IFN-alpha and IFN-beta alone or combinations of type I IFNs, type II IFNs and Ampligen can be effective in inhibiting the growth of glioma cells.

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The Cellular Effects of Interferon

Cited by 27 publications

References 154 publications

Treatment of lymphoblastoid cells with interferon decreases insulin binding

Treatment of lymphoblastoid cells with interferon decreases insulin binding

Murine interferon-beta receptor-mediated endocytosis and nuclear membrane binding.

Sensitivities of human glioma cell lines to interferons and double-stranded RNAs individually and in synergistic combinations

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