Inhibition of transcription and translation of globin messenger RNA in dimethyl sulfoxide-stimulated Friend erythroleukemic cells treated with interferon.

Abstract

The addition of appropriate doses of interferon (IF) to cultures of Friend erythroleukemic cells inhibits dimethyl sulfoxide (Me2SO)-stimulated erythroid differentiation. In this study, the synthesis of heme, hemoglobin, and globin mRNA in Me2SO-stimulated cultures, with or without IF added, was compared. Although the hemoglobin content in Me2SO+IF-treated cultures was reduced 6- to 9-fold compared to that of cultures treated with Me2SO alone, there was less than a 2-fold decrease in the amount of heme accumulated. Globin mRNA, although unchanged in size or base sequence, was reduced in content in the Me2SO+IF cultures. The level of reduction of globin mRNA was insufficient to account for the lack of globin synthesis. Thus, it appears that IF may operate on two levels--one involving the transcription of globin mRNA and the other involving its translation.

Effect of interferon on growth and division cycle of Friend erythroleukemic murine cells in vitro.

“…Briefly, when interferon is administered on day 1 to cultures seeded in the presence of dimethyl sulfoxide, cell growth is still depressed but to a lesser extent, whereas heine and hemoglobin synthesis are inhibited two-and ninefold, respectively (23). Globin messenger RNA accumulation in cells treated with interferon plus dimethyl sulfoxide is reduced twofold, whereas globin synthesis is almost completely blocked under conditions where the overall protein synthesis is not affected (24).…”

Electrophoretically pure mouse interferon exerts multiple biologic effects.

“…It seems possible that interferon may also influence other metabolic processes such as energy utilization. In view of these considerations, it is not surprising that interferon can either inhibit or enhance certain cell functions (9)(10)(11)(12)(13)(14)(15)(16)(35)(36)(37).…”

“…In addition to interferon's well-known antiviral action, preparations of it have been reported to exert multiple effects on cells [i.e., inhibition of the multiplication of bormal and tumor cells in culture (2)(3)(4)(5), inhibition of the growth of a variety of transplantable tumors in mice (6)(7)(8), modulation of the synthesis and release of specific cellular products (9)(10)(11)(12)(13)(14)(15)(16), modification of the cell surface (17)(18)(19)(20)(21), and modulation of both the humoral (22)(23)(24)(25)(26)(27) and cell-mediated immune responses (28)(29)(30)(31)(32)(33)(34)]. Although experimental results support the hypothesis that the antiviral action of interferon is only one manifestation of its effect on cells (35)(36)(37), it is important to emphasize that these experiments were undertaken using preparations in which interferon protein constituted at most only 1% of the total protein content.…”

Interferon-induced differentiation of U937 cells. Comparison with other agents that promote differentiation of human myeloid or monocytelike cell lines.

“…In addition to its antiviral properties, the effects of interferon (IFN)' on proliferation of normal or transReceived for publication 2 April 1982 and in revised form 7 February 1983. 1 Abbreviations used in this paper: ADCC, antibody-dependent cell cytotoxicity; CRBC, chicken erythrocytes; DMSO, dimethyl sulfoxide; IFN, interferon; PMA, phorbol 12-myristate 13-acetate. formed cells and on the function of immunocompetent cells have been extensively studied (1).…”