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A Fuse

Publications and source records attributed to A Fuse.

At least 73 records · Page 4Linked to original sources
PubMed1984

Organization and structure of the mouse interleukin-2 gene.

We have cloned a chromosomal DNA segment which covers the entire sequence for the murine interleukin-2 gene and analysed the structure of the gene. The coding regions are separated into four blocks by three introns each of which is located similarly to the corresponding human gene. The exon sequences can be aligned perfectly with the previously cloned cDNA sequence. Of particular interests is the presence of sequences within the 5'-flanking region which are highly conserved between mouse and man. The conserved region which spans more than 400 base pairs may play a role in the regulation of IL-2 gene expression.

Amino Acid Sequence↗
PubMed1984

Expression of the anti-retrovirus action of interferon in human cells which exhibit a reduced number of receptors for interferon.

The anti-viral and anti-cell fusion actions of human gamma interferon (IFN) were examined on human rhabdomyosarcoma cells and compared with the actions of IFN-alpha. Treatment of A204 and RD114-C1 cells with IFN-gamma resulted in significant inhibition of retrovirus production and cell fusions which were induced by Sendai virus, but IFN-gamma did not induce 2'-5' oligoadenylate (2-5A) synthetase or dsRNA-dependent protein kinase, and failed to inhibit EMC virus replication in RD114-C1 cells as previously observed on IFN-alpha treatment (Tomita, Y. et al. (1982) Virology 120, 258-263). Although IFN-gamma induced 56K protein more strongly than IFN-alpha in human transformed HEp-2, HeLa, RSa, IFr, and A204 cells, no significant induction of this protein was observed in RD114-C1 cells after IFN-alpha or IFN-gamma treatment. Specific bindings of 125I-labeled human IFN-alpha A to HeLa, A204 and RD114-C1 cell surfaces showed that the numbers of the binding sites on RD114-C1 cells were reduced to less than 22% of those on A204 cells. These results suggest that RD114-C1 cells exhibit a reduced number of receptors for IFN on the cell surface and that the receptors are functional for the expression of the anti-retrovirus and anti-cell fusion actions of IFN, but are not enough in number for expression of the anti-EMC virus action of IFN.

Antiviral Agents↗
PubMed1984

Mechanism of the stimulatory effect of phorbol 12-myristate 13-acetate on cellular production of plasminogen activator.

The human Bowes melanoma cell line secretes a plasminogen activator identical to the extrinsic tissue plasminogen activator (EPA) and different from the urokinase-like plasminogen activators mostly found in human tumor lines. In the continuous presence of 100 ng/ml of phorbol 12-myristate 13-acetate (PMA) the 24-hr production of EPA was increased 5.3-fold (average). Preincubation of the cultures for a limited time period (optimally 3 to 6 hr) also resulted in an increase of the subsequent 24-hr production. EPA produced in the presence of PMA was serologically indistinguishable from that produced spontaneously and its molecular weight as defined by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis and fibrin-agar zymography was the same as that of spontaneously produced EPA. Treatment of the cells with actinomycin D inhibited PMA-induced EPA production. Also, RNA extracted from PMA-treated cells became enriched in mRNA for EPA. It is concluded that PMA acts by enhancing the transcription of the EPA gene. Cell-associated EPA levels were increased, even when tested as early as 3 hr after initiation of the PMA treatment, thus failing to support the view that increased EPA synthesis occurred as a result of depletion of the cellular pool.

Cell Line↗
PubMed1984

Binding of 125I-labeled human interferon to cell lines with low sensitivity to interferon.

Iodinated human interferon alpha A (HuIFN-alpha A) was found to bind specifically to IFN-sensitive RSa cells: the dissociation constant was 8.7 X 10(-10)M and the estimated number of receptor sites per cell was 1110. Seven cell lines that were either insensitive or of low sensitivity to the antiproliferative effect of IFN were found to contain a much smaller (3- to 4-fold) number of receptor sites, but the dissociation constants of these binding sites were of the same order of magnitude as those of receptors on RSa cells. Under the present experimental conditions, cell resistance to the antiproliferative effect of IFN is closely associated with the number of receptor sites.

Binding, Competitive↗
PubMed1982

Effect of glycolipids and glycophorin on the activity of human interferon-beta and -gamma.

We have studied neutralization of the antiviral activity of human fibroblast (IFN-beta) and immune interferon (IFN-gamma) by incubation with glycolipids (including the gangliosides GM1, GM2 and GM3, as well as various other glycolipids) and with the sialoglycoprotein, glycophorin. When 100 units/ml of IFN-beta were preincubated with 30-80 microM of the gangliosides, all antiviral activity was abolished. Similarly, 120 microM of glycophorin completely reversed the antiviral activity of 100 units/ml of IFN-beta. Glycolipids containing more than two sugars also showed moderate inhibitory effects. GM2 at a concentration of 200 microM almost completely inhibited the antiviral activity of 100 units/ml of IFN-gamma, but GM1, GM3 and glycophorin had only a moderate inhibitory effect. These results suggest that the terminal N-acetylneuraminic acid (NANA) residues of gangliosides and of glycophorin play an important role in the inhibition of IFN-beta, and that they may be similarly involved in the inhibition of IFN-gamma.

Binding Sites↗
PubMed1982

Mechanism of stimulation by human interferon of prostaglandin synthesis in human cell lines.

Human interferon beta (IFN-beta) stimulated the synthesis of prostaglandin E (PGE) and prostaglandin F2 alpha in IFN-sensitive RSa and GM258 cell lines, but not in IFN-resistant HEC-1 cells. IFN-beta at a concentration of 1000 units/ml elicited 2- to 3-fold increases in PGE production in these cell lines. In the presence of exogenous arachidonic acid (1 microgram/ml), IFN-pretreated cells produced 5-fold more PGE compared to the cell cultures in the absence of arachidonic acid. Prednisolone, an inhibitor of phospholipase A2, at a concentration of 2 micrograms/ml inhibited the enhanced synthesis of PGE by IFN-pretreated cells. Indomethacin (4 micrograms/ml), a potent fatty acid cyclooxygenase inhibitor, also inhibited the increased synthesis of PGE. IFN stimulated the release of [14C]arachidonic acid from phospholipids but did not stimulate the activity of fatty acid cyclooxygenase. These data suggest that IFN stimulates prostaglandin synthesis by promoting the release of arachidonic acid from phospholipids. Since cycloheximide and actinomycin D inhibited the stimulation of PGE synthesis, the stimulation of prostaglandin synthesis by IFN seemed to be due to de novo enzyme synthesis which catalyzes the release of fatty acid. Addition of exogenous PGE suppressed the growth of RSa and GM258 cells. Prednisolone and iodomethacin partially inhibited anti-cell growth activity of IFN, suggesting a possibility that IFN-inhibited cell growth was partly mediated by prostaglandin.

Arachidonic Acid↗
PubMed1981

Inhibitory effect of cholera toxin on human natural cell-mediated cytotoxicity and its augmentation by interferon.

Cholera toxin inhibits human natural cell-mediated cytotoxicity in a dose- and time-dependent manner. Pretreatment of lymphocytes with 10 ng/ml of cholera toxin for 2 h almost completely inhibited cytolysis. Interferon augmented human natural cell-mediated cytolysis, but when lymphocytes were pretreated with cholera toxin before interferon treatment, no enhancement of cytolysis occurred. Cholera toxin could inhibit the enhancement of cytolysis by interferon even when lymphocytes were treated with cholera toxin after 2 h interferon treatment. Cholera toxin subunit B which binds cell surface ganglioside galactosyl-N-acetylgalactosaminyl - [N-acetylneuraminyl] - galactosylglucosylceramide (GM1) without activating adenyl cyclase had no effect either on natural cytolysis or on the enhancement of natural cytolysis by interferon, suggesting that mere binding of cholera toxin to the cellular receptor was not enough to inhibit natural cell-mediated cytolysis. Cyclic adenosine 3',5'-monophosphate (cAMP) levels increased in cholera toxin-treated lymphocytes and the time course of cAMP accumulation was similar to that of cytotoxicity inhibition. Exogenous dibutyryl-cAMP (db-cAMP) and theophylline inhibited cytolysis, while exogenous dibutyryl cyclic guanosine 3',5'-phosphate (db-cGMP) enhanced cytolysis slightly, suggesting that the process of inhibition of human natural cell-mediated cytolysis was at least partly modulated by intracellular cyclic nucleotides.

Cells, Cultured↗
PubMed1981

A UV-sensitive human clonal cell line, RSa, which has low repair activity.

The repair activity of a human transformed cell line, RSa, which was found to be highly sensitive to the lethal effects of 254 nm far-ultraviolet radiation, was compared with that of HeLa cells by evaluating the range of UV-induced incorporation of [methyl-3H]thymidine ([3H]dThd) or 5-[6-3H]bromodeoxyuridine ([3H]BrdUrd) into deoxyribonucleic acid. Direct scintillation counting was used for measuring the extent of unscheduled DNA synthesis (UDS) in UV-irradiated cells, which were treated with hydroxyurea or with arginine deprivation. More quantitative measurements were made by using the density labeling and equilibrium centrifugation method for assaying repair replication. All the amounts of UDS and repair replication in RSa cells were markedly below those in HeLa cells. The possible relationships of the low repair activity to abnormally high UV sensitivity in RSa cells are discussed.

Cell Line↗
PubMed1981

Resistance to interferon of a human adenocarcinoma cell line, HEC-1, and its sensitivity to natural killer cell action.

A human endometrial cancer cell line, HEC-1, was found to be resistant to the antiviral and anticellular action of interferon. However, HEC-1 cells were susceptible to the cytotoxicity of natural killer (NK) cells, and interferon enhanced such NK activity. When HEC-1 cells were treated with interferon, sensitivity of HEC cells to the cytotoxicity of NK cells was not suppressed.

Adenocarcinoma↗
PubMed1980

Effects of concanavalin A on the antiviral and cell growth inhibitory action of human interferons.

Sensitivities of human transformed cell line RSa and its variant cell line IFr to the cytotoxicity of Con A were compared. IFr cells were more resistant than RSa to Con A. Con A-resistant cell lines, Con Ar-1 and Con Ar-3, were isolated from RSa, and they were slightly more sensitive than RSa cells to the cell growth-inhibitory actions of interferons. Agglutinability of RSa, IFr, and Con Ar cells by Con A was compared and found to be almost equal. The combined effects of Con A and interferon upon growth and viability of these cell lines were tested. When RSa and IFr cells were treated simultaneously with Con A and Le-IF, growth of the cells was suppressed more markedly than when treatment was with Con A or Le-IF alone. To clarify the mechanism of this phenomenon, binding of 125I-labeled Con A was examined. Though ther wee some differences, both leukocyte and fibroblast interferon enhanced the binding of Con A to RSa cells and also in Con Ar cells but, in interferon-resistant IFr and HEC cells, enhancement of Con A binding was low or not observed. Therefore, the combined effect of Con A and interferon on the inhibition of cell growth is not considered to be merely due to the enhanced binding of Con A by interferon action. Successive treatment of RSa or Con Ar cells with Con A and interferon did not enhance the antiviral action of interferon at all. On the contrary, simultaneous treatment with Con A and interferon suppressed the antiviral action of interferon, depending on the concentration of Con A used. Thus, the effect of Con A on the antiviral and cell growth-inhibitory actin of interferon seems rather different.

Cell Aggregation↗
PubMed1979

Comparison of the suppression of cell and virus growth in transformed human cells of leukocyte and fibroblast interferon.

The effects of human leukocyte interferon (Le-IF) and fibroblast interferon (F-IF) on the growth of the transformed human cell lines, RSa and RSb, were compared. Both were considerably more sensitive to F-IF than to Le-IF. Two cell lines, IFr and F-IFr, derived from the RSa cell line, were resistant to the anticellular effects of Le-IF, but less resistant to those of F-IF.

Cell Division↗
PubMed1979

Effect of cholera toxin on the antiviral and anticellular activities of human leukocyte interferon.

Cholera toxin added into cell cultures together with human leukocyte interferon inhibited the establishment of the antiviral state by interferon but not the anticellular activity of interferon in human cells. Sensitivities of various human cell lines to anticellular activities of interferon and cholera toxin were compared, but no direct correlation between both activities were demonstrated. These results suggest that antiviral and anticellular activities of interferon are due to different mechanism of actions, and cholera toxin does not act directly on the receptor site for interferon.

Cell Division↗