Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We present evidence showing that TNF is capable of inducing an antiviral state in WISH cells thereby protecting them from the cytopathic effect of vesicular stomatitis virus. Establishment of the antiviral state requires pretreatment with TNF. Such pretreatment not only protects the cells in a dose-dependent manner, but it markedly reduces virus yield as well. Kinetic studies have shown that a pretreatment period as short as 4 h at 37 degrees C is effective in conferring protection. The antiviral activity of TNF could be attributed to the induction of IFN-beta. In fact, polyclonal antibodies to IFN-beta completely neutralized the antiviral state elicited by TNF. 2-5A synthetase activity was significantly enhanced when the cells were treated with doses of TNF that afforded antiviral protection. Finally, addition of specific antibodies to IFN-beta 2 (IL-6) during TNF pretreatment failed to abolish the antiviral state, thus suggesting that IFN-beta 2 is not involved in the TNF-induced antiviral state. Also, a homogeneous IFN-beta 2 preparation failed to exert antiviral activity in our cell system.
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PMID:The in vitro antiviral activity of tumor necrosis factor (TNF) in WISH cells is mediated by IFN-beta induction. 254 88

We find that pretreatment of WISH cells with tumor necrosis factor (TNF)-alpha, IL-1, and lymphotoxin/TNF-beta is capable of inducing an antiviral state in these cells, thereby protecting them from vesicular stomatitis virus cytopathic effect. Furthermore, we find that such a treatment causes a major inhibition of the synthesis of VSV proteins, as analyzed by SDS-PAGE. The 2-5A synthetase activity is also increased by treating the cells with doses of cytokines effective in antiviral protection. In this cell system, inclusion of polyclonal antibodies to IFN-beta during cytokine pretreatment abrogates the antiviral state elicited by the above cytokines, while antibodies to IFN-beta 2/IL-6 fail to abolish the cytokine-induced antiviral effects.
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PMID:Comparative study on the antiviral activity of tumor necrosis factor (TNF)-alpha, lymphotoxin/TNF-beta, and IL-1 in WISH cells. 254 53

Interferons inhibit the replication of vesicular stomatitis virus (VSV), but not of encephalomyocarditis virus (EMCV), in mouse JLSV-11 cells. We report the isolation of clonal derivatives from this cell line in which the replication of both viruses is impaired by interferons. These clones were selected from the parental line by virtue of their rescue by interferon treatment from the cytopathic effects of EMCV infection. In one such clone, RK8, the replication of VSV and EMCV and the production of resident murine leukemia virus were inhibited by interferon. On the other hand, in clone RK6, which was isolated without any selection, the replication of VSV, but not of EMCV, was impaired by interferons. The levels of 2'-5'-oligoadenylate synthetase mRNA and enzyme activity were similarly elevated upon interferon treatment in the two clones. However, the level of RNase L, as determined by binding and cross-linking of a radiolabeled 2'-5'-oligoadenylate derivative, was much lower in RK6 cells than in RK8 cells. In accord with this observation, the introduction of 2'-5'-oligoadenylates into cells inhibited protein synthesis much less strongly in RK6 cells than in RK8 cells. These results are consistent with the notion that the 2'-5'-oligoadenylate-dependent RNase L may be a mediator of the inhibition of EMCV replication by interferons.
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PMID:Studies on the role of the 2'-5'-oligoadenylate synthetase-RNase L pathway in beta interferon-mediated inhibition of encephalomyocarditis virus replication. 284 70

Pretreatment of mouse embryo fibroblasts (MEF) with recombinant murine interferon-beta (rMuIFN-beta) induced a high level of intracellular 2',5'-oligoadenylate (2-5A) synthetase activity. However, murine cytomegalovirus (MCMV) replicated under such condition, indicating that MCMV is relatively insensitive in vitro to rMuIFN-beta. Thus, there was a dissociation of 2-5A synthetase activity and antiviral activity against MCMV. In contrast to MCMV, the two parameters were closely associated in the case of vesicular stomatitis virus (VSV).
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PMID:Effect of recombinant murine interferon-beta on the replication of murine cytomegalovirus. 285 Apr 48

A number of Friend leukemia cell variants with a interferon-gamma (IFN-gamma)-resistant phenotype have been isolated. They appear resistant to the antiproliferative action of IFN-gamma and to the induction of the antiviral state assessed by Friend leukemia virus release and vesicular stomatitis virus yield. Selection was performed via a prolonged exposure to increasing amounts of highly purified recombinant IFN-gamma of wild-type Friend cells or of variant clones thereof already resistant to IFN-alpha/beta (Affabris et al., 1982, Virology 120, 441-452). Only the clones derived from IFN-alpha/beta-resistant variants showed a phenotype fully resistant to IFN-gamma treatment while keeping their previously acquired resistance to IFN-alpha/beta. These cells are not deficient in high-affinity receptors for IFN-gamma so that their resistant phenotype appears to be mediated by events distal to binding of IFN-gamma to its receptors. Furthermore, analysis of IFN-induced dsRNA-dependent 2-5A synthetase and 67K protein kinase enzymatic activities, biochemical markers for cellular responses to IFN, showed that both these activities were not induced in IFN-alpha/beta and IFN-gamma-resistant clones when treated with either type of IFN. Accordingly, no increased expression of 2-5A synthetase mRNA(s) could be detected by probing poly(A)+-enriched RNA from cells exposed to IFN-alpha/beta or IFN-gamma treatment with murine or human specific cDNAs. On the other hand, no major changes in restriction patterns of 2-5A synthetase gene(s) were observed in these variant cells by restriction endonuclease digestion and Southern blotting. In addition, analysis of 2-5A synthetase mRNA induction, performed on wild-type cells, showed that the kinetic of induction due to IFN-gamma treatment is slower than that obtained with IFN-alpha/beta.
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PMID:Interferons-alpha/beta- and -gamma-resistant Friend cell variants exhibiting receptor sites for interferons but no induction of 2-5A synthetase and 67K protein kinase. 296 42

Using radioiodinated murine interferon-gamma (IFN-gamma), various cell lines were analyzed for their capacity to bind IFN-gamma and to respond to its biological activity as measured by activation of the 2',5'-oligoadenylate (2-5A) synthetase, induction of the antiviral activity, and inhibition of [3H]thymidine uptake. A T-cell lymphoma, EL-4, was found to express relatively high number of specific membrane receptors for IFN-gamma (60,000/cell) with a dissociation constant of around 9 X 10(-10) M. By contrast, a fibroblast cell line, K-BALB, transformed by the Kirstein murine sarcoma virus, was found negative for binding of radioiodinated IFN-gamma, even in the presence of high ligand concentrations. Other cell lines displayed numbers of receptors varying between 650 to 20,000 binding sites/cell with KD ranging between 5 X 10(-9) to 9 X 10(-10) M. When incubated with EL-4 expressing high levels of specific receptors, IFN-gamma caused stimulation of cell growth, but not resistance to viral (vesicular stomatitis virus) infection and expression of 2-5A synthetase. By contrast, when L1210 and TS/A cells, expressing intermediate levels of specific receptors, were incubated with IFN-gamma, inhibition of cell growth, induction of antiviral resistance and activation of 2-5A synthetase was observed. Finally, K-BALB cells, lacking specific receptors for IFN-gamma, were completely unsensitive to its biological activity. The present system could represent a useful model for the characterization of the interaction of IFN-gamma with target cells at molecular levels.
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PMID:Functional characterization of murine cell lines expressing high, intermediate, or negative levels of surface receptors for interferon-gamma. 297 May 10

Injection of conventional or axenic weanling mice with potent sheep or goat antibody to mouse interferon alpha/beta resulted in a decrease in the basal level of 2-5A synthetase in resting peritoneal macrophages and rendered these cells permissive for vesicular stomatitis virus. There was a good inverse correlation between the level of 2-5A synthetase in peritoneal macrophages and the permissivity of these cells for vesicular stomatitis virus. The peritoneal macrophages of 1- and 2-week-old mice had low levels of 2-5A synthetase and were permissive for vesicular stomatitis virus, whereas at 3 weeks (and after) there was a marked increase in the level of 2-5A synthetase in peritoneal macrophages, and these cells were no longer permissive for vesicular stomatitis virus. We suggest that low levels of interferon alpha or beta or both are produced in normal mice, and that this interferon contributes to host defense by inducing and maintaining an antiviral state in some cells.
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PMID:Injection of mice with antibody to mouse interferon alpha/beta decreases the level of 2'-5' oligoadenylate synthetase in peritoneal macrophages. 298 40

Platelet-derived growth factor (PDGF) stimulates expression of a "competence" gene family in Balb/c-3T3 cells. The competence family contains the c-myc and c-fos genes together with several functionally uncharacterized genes (JE, KC, and r-fos) that have been isolated as cDNA clones. We show that double-stranded ribonucleic acid is a potent inducer of the competence gene family. Infection with vesicular stomatitis virus also induces expression of this gene family. Conversely, PDGF stimulates expression of genes hitherto characterized as responsive to double-stranded ribonucleic acids, including the beta-fibroblast interferon and (2'-5')-oligoadenylate synthetase genes. These PDGF-inducible genes could conceivably function in a feedback loop to control 3T3 cell growth. Some of the genes, such as c-fos and c-myc, are induced quickly by PDGF and may initiate a round of cell division. Others, such as beta-fibroblast interferon and (2'-5')-oligoadenylate synthetase, are induced more slowly and may function as feedback inhibitors of the growth response to PDGF.
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PMID:Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. 300 Jun 15

The kinetics of the biologic response following a single intramuscular injection of 18 X 10(6) units of recombinant human interferon-alpha 2a (rHuIFN-alpha 2a) was investigated during 11 courses in 10 healthy individuals. Serial peripheral blood mononuclear cell (PBM) samples were assayed for their biologic responsiveness to rHuIFN-alpha 2a by measuring both their 2',5'-oligoadenylate (2-5A) synthetase activity and their resistance to in vitro vesicular stomatitis virus (VSV) infection. A significant increase in 2-5A synthetase levels occurred at 6 h, and enzyme levels returned to baseline values between 96 and 104 h postinjection. Protection of PBMs from VSV infectivity began within 1 h and lasted up to 144 h postinjection. The clinical side effects induced by IFN administration and serum IFN levels were not parallel over time with the antiviral effects observed. This study defines the time course of the biologic response induced by rHuIFN-alpha 2a in healthy volunteers. A parallel time course between the induction of 2-5A synthetase activity and the development of the antiviral state in PBMs was demonstrated.
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PMID:Time course of interferon levels, antiviral state, 2',5'-oligoadenylate synthetase and side effects in healthy men. 303 34

CHO cell lines that constitutively produce the murine interferon-alpha (IFN-alpha) subspecies alpha 4 and alpha 6 were constructed. The producer cell lines were protected against viral (vesicular stomatitis virus) infection by the IFN species secreted, but were resistant to the growth inhibitory activity of the IFN species. As compared with alpha 4, the alpha 6 protein displayed a high antiproliferative activity when added to normal CHO cells, which correlates completely with the high antiviral activity of alpha 6 on these cells. Three messenger ribonucleic acid (mRNA) species, which are normally induced in CHO cells by IFN treatment (1-8, 2-5A synthetase, and ISG 15) were constitutively present in CHO producer cell lines. The level of another mRNA (ISG 54), however, was very low in the producer cells as compared with its expression in short-term IFN-treated cells. These data indicate that 1-8, 2-5A synthetase and ISG 15 are not involved in the antigrowth activity of IFN in this system, but rather suggest a function of ISG 54 in this respect.
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PMID:Interferon-alpha-(IFN) producing CHO cell lines are resistant to the antiproliferative activity of IFN: a correlation with gene expression. 324 Oct 15


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