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)

An ex vivo antiviral assay was established which uses hepatocytes from mice given recombinant mouse interferon-beta (rmIFN-beta). Assay results were compared with results obtained with a 2',5'-oligoadenylate synthetase (2-5AS) assay. rmIFN-beta was intraperitoneally administered to C3H mice and the antiviral state of their liver parenchymal cells was evaluated in an in vitro cytopathic effect assay. In this assay, cells are infected with vesicular stomatitis virus (VSV) and surviving cells are determined colorimetrically. The antiviral state was measured as the resistance of hepatocytes to VSV infection with increasing doses of rmIFN-beta. The antiviral state correlated well with the dose-dependent increase in hepatic 2-5AS activity. This good correlation suggests that induction of 2-5AS mediates the antiviral action of interferon in liver tissue. This ex vivo assay could be a useful tool for estimating the ability of hepatocytes to resist hepatitis virus infection.
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PMID:An ex vivo assay for estimating the antiviral state of hepatocytes. 773 17

Recombinant equine interferon-beta 1 (reqIFN-beta 1) induces an antiviral state in blood mononuclear cells (BMC) of horses. Maximal protection against replication of vesicular stomatitis virus is achieved 6 hours after treatment with IFN in vitro and in vivo. Duration of the protective effect depends on the dose of IFN in vitro and in vivo. Availability of reqIFN-beta 1 in cultures of BMC for up to 48 hours does not prolong the antiviral state. The protective effect on BMC after treatment with IFN has similar duration in vivo and in vitro. Monitoring of the effect of IFN in vivo is, thus, simplified because the antiviral state may be recorded by testing cells twice (ie, before and 6 hours after application of interferon). All further tests may be performed in vitro. Multiple administration of reqIFN-beta 1 do not prolong duration of the protective phases after each administration. Duration of the antiviral state depends only on the dose of reqIFN-beta 1.
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PMID:Kinetics of inhibition of replication of vesicular stomatitis virus in blood mononuclear cells of horses after in vitro and in vivo treatment with recombinant equine interferon-beta 1. 797 48

In vitro culture of human monocytes results in a time-dependent differentiation into macrophages. Monocyte/macrophages were infected with HIV-1Ba-L at different times after isolation and subsequent culture. When 7-day macrophages were infected in the presence of antibodies to interferon-beta (IFN-beta), a significant increase in HIV-1 p24 release was observed. This effect was not detected in 1-day monocytes. Treatment of 7-day cultured macrophages with HIV-1 rgp120 resulted in resistance to vesicular stomatitis virus infection. This rgp120-induced antiviral state was neutralized in the presence of antibodies to IFN-beta. The overall results indicate that the infection of monocyte/macrophages with HIV-1 results in the induction of IFN-beta, which, in turn, inhibits HIV-1 expression in macrophages. The finding that HIV-1 itself (possibly through its gp120) can induce a potent antiviral factor (IFN-beta) in macrophages underlines the complex physiological function of these cells in maintaining normal homeostasis in vivo in response to virus infection.
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PMID:Role of endogenous interferon-beta in the restriction of HIV replication in human monocyte/macrophages. 808 8

Using two-dimensional electrophoresis on total and nuclear extracts of human fibroblasts, we compared polypeptide patterns of cells treated with interferon-beta (IFN-beta), IFN-gamma, or with dsRNA in the presence of anti-IFN antibodies. The analysis of whole-cell extracts revealed that, after a 6-h treatment, the three agents induce the synthesis of a common set of proteins in addition to others that are specifically induced either by IFNs or by dsRNA. After a 15-h treatment, this common set of proteins was only induced by IFNs. Furthermore, at this time, IFNs also regulated proteins whose synthesis was specifically induced or repressed by poly(I).poly(C) in the 6-h treated cells. These results indicate that poly(I).poly(C) regulates protein expression more rapidly and more transiently than IFNs. The analysis of nuclear extracts showed similar differential kinetics of protein expression. However, a greater number of polypeptides was found to have their synthesis specifically induced by dsRNA. Moreover, poly(I).poly(C) was found to be mitogenic in these cells and did not induce a significant resistance to vesicular stomatitis virus (VSV). This study provides evidence for an overlap in the expression of proteins by dsRNA and IFNs, although these compounds do not share the same biological activities.
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PMID:Differential kinetics of polypeptide expression and different biological activities in the human fibroblast response to dsRNA or interferon treatment. 839 64

Interferon-beta (IFN-beta) strongly inhibited the expression of the hemagglutinin-neuraminidase (HN) gene of Newcastle disease virus (NDV), a paramyxovirus, in HeLa cells under the conditions where it did not affect the expression of the four upstream genes encoding the nucleocapsid protein, phosphoprotein, membrane protein and fusion protein. Even the downstream gene, encoding the large protein as well as the genome replication, appeared to be less susceptible to IFN-beta than the HN gene. This selective action of IFN-beta did not appear to be attributable to its well characterized antiviral mechanisms such as acceleration of RNA decay and translation inhibition. No similar down-regulation of a particular gene expression was found with another paramyxovirus, Sendai virus, or with a rhabdovirus, vesicular stomatitis virus, or seems to have been reported previously with any negative-strand RNA viruses. This new effect of IFN-beta thus suggests gene expression mechanism unique to NDV and may further lead to the discovery of a novel biochemical effect of IFN-beta.
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PMID:Antiviral action of interferon-beta on Newcastle disease virus: selectivity to the hemagglutinin-neuraminidase gene expression. 853 78

We previously reported that in vitro culture of human peripheral blood monocytes resulted in a time-dependent differentiation into macrophages and in an enhanced capacity for producing certain cytokines [i.e., tumor necrosis factor alpha, interleukin-6 (IL-6), and interferon-beta (IFN-beta)] in response to bacterial lipopolysaccharide (LPS). HIV-1 infection or gp120 treatment of monocyte/macrophages resulted in the induction of low levels of IFN-beta, which were very effective in restricting viral replication in 7-day cultured macrophages but not in freshly isolated cells. This enhanced response of macrophages was due to a higher sensitivity of these cells to the antiviral effect of IFN-beta. Consistent with this finding, 7-day cultured macrophages exhibited higher levels of type I IFN receptors than 1-day cultured monocytes. Treatment of monocyte/macrophages with gp120 also caused a marked increase in IL-10 secretion, regardless of the differentiation state. No IL-12 secretion was detected in monocyte/macrophage cultures treated with gp120 alone. However, consistent IL-12 secretion was found in 7-day cultured macrophages primed with IFN-beta and subsequently stimulated with gp120. Macrophages responded more efficiently than monocytes to the priming effect of IFN-beta for IL-12 production. This was consistent with a stronger antiviral response against vesicular stomatitis virus by these cells as well as with a higher expression of IFN-beta receptors. The finding that the acquisition of the macrophage phenotype is associated with an increased capacity to respond to environmental signals (such as type I and type II IFNs) underlines the importance of the differentiation process for the selection of a certain repertoire of responses that may allow these cells to have important functions in vivo.
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PMID:Induction of cytokines by HIV-1 and its gp120 protein in human peripheral blood monocyte/macrophages and modulation of cytokine response during differentiation. 922 92

The aim of this pilot study was to investigate if chemotherapy (CT) followed by the combination of interferon-beta (IFN-beta), retinoids, and tamoxifen could be effective in the treatment of metastatic breast cancer (MBC). Thirty-six patients with stage IV carcinoma of the breast were treated with six courses of cyclophosphamide, 5-fluorouracil, 4-epidoxorubicin, vincristine, and prednisone every 3 weeks (FECPV), followed by two courses of non-cross-resistant drugs, methotrexate, mitomycin C, and mitoxantrone (MMM). Treatment was continued, in responders, with low dose IFN-beta, retinyl palmitate, and tamoxifen until relapse of the disease occurred. Among 36 evaluable patients, 23 achieved a clinical response (64 %) (95 % confidence interval [c.i.] 46 %-79 %), 7 had stable disease (19%), and 6 (17%) progressed. Leukopenia occurred in 15 patients, thrombocytopenia in 6, and anemia in 11. Sixteen patients had nausea/vomiting, stomatitis was observed in 9, and diarrhea occurred in 3. Toxicity from maintenance therapy was mild and mainly hepatic. Median response duration was 31 months (range 5-107). Median overall survival was 32 months (9-108). Our study shows that this combined approach for the treatment of MBC is feasible, with an acceptable toxicity.
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PMID:Minimal residual disease in metastatic breast cancer: treatment with IFN-beta, retinoids, and tamoxifen. 947 66

We have shown previously that interferon-beta (IFN-beta) induces the alkalinization of trans-Golgi network (TGN) and inhibits the transport of G protein of vesicular stomatitis virus (VSV) in L(B) cells and gD protein of herpes simplex virus (HSV-1) in LMtk- cells transfected with gD cDNA. The vacuolar H(+)-ATPase (V-ATPase) is responsible for maintaining pH in TGN, and V-ATPase-mediated acidification is required for normal transport of proteins. To examine whether alkalinization caused by IFN is mediated through V-ATPase, the activity of V-ATPase was determined in IFN-treated cells by coupling ATP hydrolysis to NADH oxidation. Bafilomycin (Baf) was used as positive control, as it specifically inhibits V-ATPase. The activity of V-ATPase was reduced in IFN-treated or Baf-treated cells compared with untreated cells. Doses of IFN-beta or Baf that neither alter pHi nor inhibit the transport of viral glycoproteins concomitantly inhibited the transport of G and gD proteins in TGN, as demonstrated by indirect immunofluorescence studies, and raised the pH of TGN as demonstrated by a decrease in the uptake of DAMP. Further, the effect of Baf on IFN-induced antiviral activity against VSV was examined to correlate the biologic significance of these findings. Data showed that Baf significantly enhances (5-50-fold) the IFN-induced antiviral activity as demonstrated by viral titers from supernatants. These findings suggest that the inhibition of transport of G and gD proteins by IFN-beta, may be related to the inhibition of V-ATPase-mediated acidification of TGN.
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PMID:Role of vacuolar H(+)-ATPase in interferon-induced inhibition of viral glycoprotein transport. 1057 23

Here we describe the sustained expression of transgenes introduced into human embryonic stem (ES) cells using self-inactivating lentiviral vectors. At low multiplicity of infection, vesicular stomatitis virus-pseudotyped vectors containing a green fluorescent protein (GFP) transgene under the control of a human elongation factor 1alpha promoter transduced human ES cells at high efficiency. The majority of the transduced ES cells, which harbored low numbers of integrated vectors, continued to express GFP after 60 days of culture. Incorporation of a scaffold attachment region (SAR) from the human interferon-beta gene into the lentiviral vector backbone increased the average level of GFP expression, and inclusion of the SAR together with a chromatin insulator from the 5' end of the chicken beta-globin locus reduced the variability in GFP expression. When the transduced ES cells were induced to differentiate into CD34(+) hematopoietic precursors in vitro, GFP expression was maintained with minimal silencing. The ability to efficiently introduce active transgenes into human ES cells will facilitate gain-of-function studies of early developmental processes in the human system. These results also have important implications for the possible future use of gene-modified human ES cells in transplantation and tissue regeneration applications.
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PMID:High-level sustained transgene expression in human embryonic stem cells using lentiviral vectors. 1252 58

Induction of interferon-beta (IFN-beta) gene expression is a tightly regulated process, and a plethora of studies identified the signal transduction pathway TANK-binding kinase-1 (TBK-1)/IFN regulatory factor-3 (IRF-3) as essential to the induction of IFN-beta gene expression. Data regarding the role of p38 and JNK are rare, however. We investigated the contribution of these kinases to IFN-beta expression in human macrophages treated with poly(I:C), lipopolysaccharide (LPS), Sendai virus, or vesicular stomatitis virus (VSV). We found that all the stimuli induced IFN-beta mRNA, albeit to a different extent. Whereas LPS and VSV induced the phosphorylation of p38 and JNK, neither poly(I:C) nor Sendai virus led to the detection of phosphospecific signals. When inhibiting p38, a VSV-triggered IFN-beta mRNA response was inhibited, whereas inhibiting JNK suppressed an LPS-triggered response, but only when macrophages were primed with IFN-gamma. Neither poly(I:C)-induced nor Sendai virus-induced IFN-beta mRNA expression was affected when p38 and JNK were inhibited. Collectively, the data show that the contribution of p38 and JNK to the expression of IFN-beta occurs in a stimulation-specific manner in human macrophages.
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PMID:Stimulation-specific contribution of p38 and JNK to IFN-beta gene expression in human macrophages. 1789 96


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