Interferon

Ho, Monto; Armstrong, John A.; Breinig, Mary C.

doi:10.1146/annurev.mi.29.100175.001023

Cited by 137 publications

(51 citation statements)

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“…Cultures of human diploid fibroblasts (FS-4 strain) can be induced to synthesize and secrete interferon into the extracellular medium by exposure to poly-(inosinic acid)-poly(cyticylic acid) [poly(I)'poly(C)] (4)(5)(6)(7)(8). Ex-tensive studies with inhibitors of RNA or protein synthesis indicate that the regulation of interferon production in poly(I)-poly(C)-induced FS-4 cells is complex (7,(9)(10)(11).…”

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confidence: 99%

“…This repressor mechanism is thought to be responsible for the rapid shutoff of interferon production by [6][7][8] hr after induction despite the intrinsic stability of interferon mRNA (7,16,18). It has been proposed that inhibitors of macromolecular synthesis, given at appropriate times, interfere with the synthesis of components of the shutoff mechanism and hence are able to enhance interferon yield (5,7,9,10,12,14,15,18,19).…”

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confidence: 99%

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Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production

Sehgal

Dobberstein

Tamm

1977

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

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Translation of injected mRNA in oocytes of Xenopus laevis has been used as a highly sensitive and quantitative assay for interferon mRNA. Injection into oocytes of polyadenylylated RNA extracted from poly(I)poly(C)induced human diploid fibroblasts leads to the synthesis of biologically active human fibroblast interferon over a period of 24-32 hr. There is a linear relationship between the amount of mRNA injected and the interferon yield obtained over a range of 1-20 ng of injected RNA. Injection of 40-80 ng of mRNA into each of 15 oocytes, homogenized in 0.3 ml of incubation medium, gave a titer of 128-256 interferon reference units/ml of homogenate.FS-4 cells at the peak of interferon production-i.e., approximately 2.5 hr after the beginning of induction with poly(I)poly(C-gave mRNA that yielded 24-48 interferon reference units/ml in the oocyte assay (30 ng of RNA injected per oocyte). An equivalent amount of mRNA from FS-4 cells in the shutoff phase, approximately 6 hr after induction, gave <4 interferon reference units/ml. In contrast, mRNA extracted from FS-4 cells that had been induced and maintained in the presence of 40 uM 5,6-dichloro-1-j-o-ribofuranosylbenzimidazole for 6 hr produced 64-128 interferon reference units/ ml. Polyadenylylated RNA obtained from uninduced FS-4 cells did not lead to detectable interferon synthesis (<4 interferon reference units/ml). These data provide a direct verification of the hypothesis that the shutoff of interferon production in FS-4 cells involves a regulatory event leading to the posttranscriptional inactivation or degradation of interferon mRNA. Because the inactivating mechanism is sensitive to inhibition by 5,6-dichloro-1--D-ribofuranosylbenzimidazole, a selective inhibitor of nuclear heterogeneous RNA and mRNA synthesis, it is likely that synthesis of an RNA molecule is necessary for the shutoff of interferon production.

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confidence: 99%

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confidence: 99%

Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production

Sehgal

Dobberstein

Tamm

1977

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

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“…administration, high-titered IFN was detected in the lung within 15 min after administration and continued for 90 min. Thus the findings demonstrated that the maintenance of a detectable amount of IFN in mice organs is dependent on the route of administration, and the higher the titer of IFN in the lung, the higher the protective effect of IFN against influenza virus infection, mouse interferon; anti-influenza effect; distribution Distribution and metabolism of IFN in animals were well reviewed by Ho and Armstrong (1975). The clearance of IFN given to animals and man was also documented by Cantell et al (1974), Cantell andPyhala (1976) and other workers (Gresser et al 1967;Nuwer et al 1972;Pyhala and Cantell 1974;Edy et al 1976).…”

mentioning

confidence: 79%

“…Distribution and metabolism of IFN in animals were well reviewed by Ho and Armstrong (1975). The clearance of IFN given to animals and man was also documented by Cantell et al (1974), Cantell and Pyhala (1976) and other workers (Gresser et al 1967;Nuwer et al 1972;Pyhala and Cantell 1974;Edy et al 1976).…”

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confidence: 93%

Antiviral effect of interferon on influenza virus infection in mice.

Saito¹,

Suzuki²,

Ishida³

1983

Tohoku J. Exp. Med.

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The antiviral effect of highly purified mouse interferon (IFN) was studied on influenza virus infection in mice, by changing the routes of administration. By repeated intravenous (iv.) administrations of IFN, no antiviral effect was observed. However, IFN was effective when the infected mice received either intraperitoneal (i.p.) or intranasal (in.) administrations. While all of the untreated mice died within 10 days after infection, 20% of the i.p. treated mice and 67% of the i.n. treated mice survived more than 30 days. To explain these different effects after administration by different routes, the distribution of given IFN in mouse organs was examined. Fifteen min after i.v. injection, only a low-titered IFN was detected in the serum, lung, spleen and liver of the mice and soon disappeared. However, a relatively high-titered IFN was detected 30 min after i.p, administration in the lung and serum. After i.n. administration, high-titered IFN was detected in the lung within 15 min after administration and continued for 90 min. Thus the findings demonstrated that the maintenance of a detectable amount of IFN in mice organs is dependent on the route of administration, and the higher the titer of IFN in the lung, the higher the protective effect of IFN against influenza virus infection, mouse interferon; anti-influenza effect; distribution Distribution and metabolism of IFN in animals were well reviewed by Ho and Armstrong (1975). The clearance of IFN given to animals and man was also documented by Cantell et al. (1974), Cantell andPyhala (1976) and other workers (Gresser et al. 1967;Nuwer et al. 1972;Pyhala and Cantell 1974;Edy et al. 1976). Their results may be summarized as follows : (i) In the blood, IFN has an extremely rapid half-life (about 20 min), hence it is difficult to maintain elevated serum concentrations. (ii) IFN in the blood slowly decreases after repeated i.v. injections of IFN. (iii) IFN activity has been detected in the blood for more than 5 hr after i.p. administration. However, the relationship between the effect of IFN on viral infections and the distribution of IFN in the organs of these animals has never been fully investigated.Only Finter (1967) described the fact that, although intramuscular (i.m.) or i.v. injections of IFN were not effective against aerosolized influenza virus infection in mice, levels of IFN sufficient to protect against Semilki forest virus infection were obtained from the blood after those injections. On the other hand, nose-dropped IFN was found to be effective against

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“…Interferon is antiviral, has immunoregulatory effects in living cells, and inhibits cell growth [27]. IFNs have been shown to have a direct effect on the multiplication of various human tumour cells [28].…”

Section: Discussionmentioning

confidence: 99%

Phosphatidylinositol turnover is not a general regulator of neuroblastoma cell differentiation: comparison between two differentiating agents, retinoic acid and γ‐interferon

Lanciotti¹,

Cornaglia-Ferraris²,

Ponzoni³

1989

FEBS Letters

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The turnover of phosphatidylinositol (PI) is believed to constitute a crucial step in the signaling pathways for stimulation of cells by a variety of bioactive substances, including differentiating agents; however decisive evidence for the idea has not been obtained. In the present paper, we investigated the involvement of PI turnover in cell differentiation using a human neuroblastoma cell line, LAN-1, which can be induced to differentiate along the neuronal pathway by both retinoic acid (RA) and ~,-interferon (?-IFN). Analysis of labelled phosphatidylinositol metabolites from prelabelled cells indicated a rapid decrease of inositol 1,4,5-trisphosphate and 1,2-diacylglycerol within 1 min of induction of LAN-1 cell differentiation by RA, while no changes were observed in ~,-IFN-treated cells. These findings indicate the occurrence of decreased inositol phospholipid turnover in RA-treated LAN-I cells and suggest that phosphoinositide-derived metaholites may not constitute general regulators of cellular differentiation.

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Interferon

Cited by 137 publications

References 0 publications

Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production

Interferon messenger RNA content of human fibroblasts during induction, shutoff, and superinduction of interferon production

Antiviral effect of interferon on influenza virus infection in mice.

Phosphatidylinositol turnover is not a general regulator of neuroblastoma cell differentiation: comparison between two differentiating agents, retinoic acid and γ‐interferon

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