Effects of Interferon on Sensitive and Resistant L1210 Cell Lines.

Marti, Jacques; Vandenbussche, Pierre-Yves; Silhol, Michelle; Milhaud, Pierre G.; Verhaegen, Martine; Content, Jean; Lebleu, Bernard

doi:10.1089/jir.1981.1.287

Cited by 14 publications

(3 citation statements)

References 14 publications

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“…Cells of the IFN-resistant L1210 subline were shown not to express specific IFN receptors (Aguet, 1980), and IFN did not increase the level of the synthetase (Marti et aL, 1981). On the other hand, mouse embryonal carcinoma cells express specific IFN receptors that are apparently functional, as IFN increases the level of (2'-5')A synthetase, even though the cells are resistant to both the antiviral and the antiproliferative effects of IFN (Aguet et aL, 1981).…”

Section: Ipmentioning

confidence: 95%

Biological Activities and Receptor Binding of Two Human Recombinant Interferons and their Hybrids

Meister

Uzé

Mogensen

et al. 1986

Journal of General Virology

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SUMMARYTwo human recombinant lymphoblastoid interferon-0t subtypes, LylFN-B (~ts) and LyIFN-D (~q), and 10 hybrids generated therefrom were produced in Escherichia coli and purified. The antiviral and antiproliferative activities and the induction of (2'-5")oligoadenylate synthetase were compared to their receptor binding affinities. The IFN subtypes and their hybrids had similar specific antiviral activities on bovine cells. On human cells both the specific antiviral and antiproliferative activities of LylFN-B were about 30-fold higher than those of LyIFN-D. This difference in activity could be attributed partly to the N-terminal amino acids 1 to 60 and partly to amino acids 61 to 92. A third domain affecting the biological activities was found within the carboxyproximal segment from amino acids 93 to 150. The differences in these activities were found to correlate with their ability to bind the receptor, suggesting that the differences in activity might be due to altered binding of the IFNs to the cellular receptors. In contrast, the induction of (2'-5')oligoadenylate synthetase did not follow the same activity profile. On mouse cells, the efficiency of the hybrids was affected by at least four sites on the IFN protein. A hybrid with the N-terminal segment 1 to 60 from IFN-B and amino acids 61 to 166 from IFN-D had a specific antiviral activity on mouse cells as high as on human cells corresponding to a 500-and 5000-fold increase in specific activity compared to IFN-D and IFN-B, respectively. We suggest that on mouse cells the IFN activity may be more dependent on conformational differences than on human cells, which in turn might reflect a less precise fit to the mouse receptor than to the human receptor.

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Section: Ipmentioning

confidence: 95%

Biological Activities and Receptor Binding of Two Human Recombinant Interferons and their Hybrids

Meister

Uzé

Mogensen

et al. 1986

Journal of General Virology

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“…All p2-M serum levels during treatment were higher, but never sta¬ tistically significantly so, than baseline. Because 2',5'OAS plays a leading role in the antiviral and antiproliferative action of jpjsi (36)(37)(38)(39)(40) ;ts I/2 V|-v0 behavior has been repeatedly investigated in the cells and serum of IFN-treated patients.' 6-32"33-35-41' We docu¬ mented increases in both serum and intracellular 2',5'A during IFN treatment, which is in line with previous reports by our¬ selves and others.…”

Section: Discussionmentioning

confidence: 99%

Interferon-α-Induced Biologic Modifications in Patients with Chronic Myelogenous Leukemia

Liberati¹,

Horisberger

Garofani

et al. 1994

Journal of Interferon Research

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Serum neopterin (Np), beta 2-microglobulin (beta 2-M), and 2',5'-adenylate (2',5'A) levels and intracellular 2',5'A and human Mx (Hu-Mx) protein synthesis were measured in 20-24 chronic myeloid leukemia patients before and during 1 year of IFN-alpha treatment and in a further 8-9 patients before and at the end of the first and second treatment weeks only. Univariate analysis showed that IFN-alpha increased Np and 2',5'A serum levels and intracellular concentrations of 2',5'A and Hu-Mx significantly from the end of the first week to month 12 of therapy. The biologic marker profiles were similar in cytogenetic responders and nonresponders, as well as in patients treated with IFN-alpha early (< 12 months from diagnosis) or late (after > 12 months standard chemotherapy). Further, there were no differences in the short-term (first 14 days) or long-term (during 12 month therapy) induction of the biologic markers irrespective of whether IFN-alpha 2a or IFN-alpha 2b was given. Because multivariate analysis revealed no significant interactions between cytogenetic response, time to treatment, and type of IFN-alpha used, increments in intracellular 2',5'A and Hu-Mx protein were similar at all study times for all factor combinations tested. Np levels varied significantly only during the first 14 therapy days; changes in serum 2',5'A were never statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Cell extracts were made as previously described [14]. Protein concentrations were determined according to the method of the cell lysate was spun at 30,000 g for 30 min and the supernatant used as a source of 2'5'-oligoadenylate polymerase.…”

Section: Cell Extractsmentioning

confidence: 99%