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

WISH and Hep-2 cells were incubated in an environment with atmospheric oxygen (20% O2, approximately 140 mmHg partial pressure), and under hypoxic conditions (2% O2, approximately 14 mmHg). The oxygen tension greatly affected the metabolism of the cells and their response to interferon-alpha (IFN-alpha) and IFN-gamma. Under hypoxic conditions, the cytopathogenicity of vesicular stomatitis virus (VSV) was reduced by about 50%, and the antiviral effects of the interferons (IFNs) were increased, both in terms of VSV-induced cytopathic effect (CPE), and yields of infectious virus. Local hypoxia is a nonspecific host defense against virus infection. The present results suggest that one of the mechanisms is by potentiation of the effects of the IFN produced at the sites of virus replication.
 ...
PMID:Hypoxia enhances the antiviral activity of interferons. 838 91

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.
 ...
PMID:Differential kinetics of polypeptide expression and different biological activities in the human fibroblast response to dsRNA or interferon treatment. 839 64

The antiviral relevance of soluble mediators that may operate in the vicinity of virus specific effector T cells was investigated. Mice were immunized with vesicular stomatitis virus (VSV) wild type (wt) and subsequently challenged with a mixture of two vaccinia recombinant viruses, one expressing the nucleoprotein of VSV (vacc-VSV-NP) the other expressing the glycoprotein of lymphocytic choriomeningitis virus (vacc-LCMV-GP). It was determined whether or not the VSV wt-induced memory T cell response that is protective against vacc-VSV-NP would inhibit growth of the nonrecognized vacc-LCMV-GP. In ovaries and testes replication of vacc-LCMV-GP was not inhibited. In contrast, the T cell response against vacc-VSV-NP nonspecifically inhibited growth of the non-recognized vacc-LCMV-GP in the central nervous system. This inhibiting effect was partly abrogated by treatment with anti-IFN-gamma antiserum but not by an anti-TNF-alpha antiserum. Similar results were obtained in VSV wt-immune H-2b mice, which eliminate vacc-VSV-NP by CD8+ T cells and in H-2k mice, which eliminate vacc-VSV-NP by a CD4+ T cell-dependent mechanism. These data suggest that a protective bystander effect mediated by soluble CD8+ and CD4+ T cell-dependent factors may be demonstrated against vaccinia virus only in an organ such as the central nervous system in which the blood-brain barrier inhibits diffusion and draining of the soluble antiviral factors released by specific effector T cells.
 ...
PMID:T cell-dependent IFN-gamma exerts an antiviral effect in the central nervous system but not in peripheral solid organs. 845 Feb 14

In vitro, T cell-dependent cytotoxicity is mediated by two distinct mechanisms, one being perforin-, the other Fas-dependent. The contribution of both of these mechanisms to clearance of viral infections was investigated in mice for the non-cytopathic lymphocytic choriomeningitis virus (LCMV) and the cytopathic vaccinia, vesicular stomatitis (VSV) and Semliki forest (SFV) viruses. Clearance of an acute LCMV infection was mediated by the perforin-dependent mechanism without measurable involvement of the Fas-dependent pathway. For the resolution of vaccinia virus infection and for resistance against VSV and SFV, however, neither of the two pathways was required. These data suggest that perforin-dependent cytotoxicity mediated by T cells is crucial for protection against non-cytopathic viruses, whereas infections with cytopathic viruses are controlled by nonlytic T cell-dependent soluble mediators such as cytokines (IFN-gamma against vaccinia virus) and neutralizing antibodies (against VSV and SFV).
 ...
PMID:The roles of perforin- and Fas-dependent cytotoxicity in protection against cytopathic and noncytopathic viruses. 856 9

Corticostatins/defensins are a family of cationic peptides recently isolated from phagocytotic cells of the myeloid lineage. Natural killer (NK) cells are spontaneously cytotoxic large granular lymphocytes that are involved in immunosurveillance against cancer and infections. Their activity is modulated by hormones of the hypothalamic-pituitary-adrenal axis. We wished to determine whether two human corticostatins/defensins, HP-1 and HP-4, are able to change in vitro the spontaneous NK activity of human peripheral blood mononuclear cells (PBMC) and the responses either to the stimulatory cytokines immune interferon (IFN-gamma) or interleukin 2 (IL-2) and to the inhibitory hormone cortisol. NK cell activity was measured in a 4-h direct cytotoxicity assay with K562 cells as a target. HP-1 and HP-4 (10 (-8) -10 (-9) M) significantly inhibited the spontaneous and cytokine-inducible NK activity, and increased the cortisol-dependent inhibition. Radioimmunoassay of HPLC purified fractions obtained from sonicated NK cells showed HP-1 in the two cell preparations examined. We also evaluated the effects of HP-1 and HP-4 (10 (-8) M -10(-9) M) upo IFN-gamma and interleukin 6 (IL-6) production by PBMC stimulated with phytohemagglutinin (PHA) or concanavalin A (ConA). IFN-gamma was titrated with the biological assay using WISH cells as indicators and vescicular stomatitis virus (VSV) as the challenge virus. IL-6 was measured using an enzyme amplified sensitivity immunoassay. Both HP-1 and HP-4 significantly reduced cytokine production. Our data indicate that corticostatins/defensins are novel modulators of lymphocyte functions in vitro. Their immunodepressing properties could add complexity and plasticity to hypothalamic-pituitary-adrenal-cytokine circuits in vivo.
 ...
PMID:Corticostatins/defensins inhibit in vitro NK activity and cytokine production by human peripheral blood mononuclear cells. 873 77

Mice lacking the receptor for type I interferon (IFN-alpha beta, A129 mice), for type II interferon (IFN-gamma, G129 mice) or for both receptors (AG129 mice) have been generated by embryonic stem cell mediated gene targeting and inter-crossing A129 x G129, respectively. The role of the two IFN systems in controlling a range of infections has been studied using these mice. Type I IFN is shown to be responsible for the immune defence against most viral infections tested (Lymphocytic Choriomeningitis Virus, Semliki Forest Virus, Theiler's Virus, Vesicular Stomatitis Virus), type II IFN seems to be of little importance. In Vaccinia Virus and Theiler's Virus infection, however, both IFN systems were found to play a nonredundant role. IFN-gamma was critical for the defence against intracellular bacteria (Mycobacterium, Listeria) and parasites (Leishmania), whereas IFN-alpha beta was not. IFN-alpha beta is produced by virus-infected cells within hours and plays an important role in preventing virus spread early. Production of IFN-gamma on the other hand needs activation of the immune system and plays a major role later, i.e. mostly during the immune response. Data obtained with the mice described here show that both IFN systems seem to have evolved to complement each other in the host defence against a wide variety of infectious agents.
 ...
PMID:Immune defence in mice lacking type I and/or type II interferon receptors. 882 79

Effects of exogenous cytokines on replication of vesicular stomatitis virus (VSV) in amniotic membrane and placental organ cultures (OC) were studied. We compared the effects observed in OC and established human carcinoma cell lines: A549 and HEp-2. Recombinant human tumor necrosis factor alpha (rHuTNF-alpha), added to amniotic membrane, villous, or decidual OC at concentrations of 30 to 3000 U/ml, potentiated VSV replication by 10-1000 fold. Addition of 5 to 10000 U/ml of recombinant human interleukin 6 (rHuIL-6) to OC from 5 placentas was without effect on VSV growth, except one culture in which enhanced VSV replication has been observed. rHuTNF-alpha was found to have no effect on VSV growth in HEp-2 and A549 cell cultures. In contrast, the placental OC were sensitive to antiviral activity of natural interferons (IFNs): alpha, beta and recombinant IFN-gamma, although A549 cells were 5 to 10 fold more responsive to the cytokines.
 ...
PMID:Effect of exogenous tumor necrosis factor alpha, interleukin 6 and interferons on vesicular stomatitis virus replication in human placenta and amniotic membrane organ cultures. 887 71

IFN-gamma is a pleiotropic cytokine that plays a major role in anti-infectious immune responses. The physiologic effects of IFN-gamma are thought to be mediated by the binding of extracellular IFN-gamma to its receptor at the cell surface, thereby triggering an intracellular signaling cascade. In this work, we present evidence for a completely intracellular mechanism for IFN-gamma to induce virus protection. Murine fibroblasts were transfected with the cDNA for murine IFN-gamma, and although no detectable amounts of IFN-gamma were released, these cells were resistant to lysis by the cytolytic vesicular stomatitis virus. In contrast to exogenously added IFN-gamma, the effect of the endogenously produced IFN-gamma was not abolished by treatment with neutralizing Abs. To test whether intracellular signal transduction occurs, an IFN-gamma variant was constructed with the carboxyl-terminal endoplasmic reticulum retention signal Lys-Asp-Glu-Leu (KDEL). Transfection of fibroblasts with this mutant IFN-gamma, anchored in the endoplasmic reticulum, led to virus resistance, thus demonstrating that biologic effects of this protein do not necessarily require binding to the receptor at the cell surface. However, the antiviral state induced by transfection with IFN-gamma-KDEL was strictly dependent on the presence of the IFN-gammaR, since fibroblasts derived from IFN-gammaR-deficient mice (IFN-gammaR -/-) were not rendered virus resistant. The virus resistance induced was accompanied by enhanced expression of 2'-5' oligoadenylate synthetase and constitutive activation of STAT1 (signal transducers and activators of transcription). Hence, autocrinous effects of IFN-gamma in cells naturally producing this cytokine might occur even in the absence of its secretion. The mechanisms involved in signaling appear to be identical with or closely related to those occurring after binding of IFN-gamma to its receptor at the cell surface.
 ...
PMID:Intracellular murine IFN-gamma mediates virus resistance, expression of oligoadenylate synthetase, and activation of STAT transcription factors. 890 36

The antiviral immunity of human placenta and amniotic membrane in an organ culture (OC) system was studied. Freshly isolated explants of most of the placentas at term and the amniotic membranes were found to be relatively resistant to herpes simplex virus type 1 (HSV-1), encephalomyocarditis virus (EMCV), and vesicular stomatitis virus (VSV) infections. After in vitro aging, however, the OC acquired the sensitivity to the viruses. In about 66%-90% of placentas, resistance of freshly isolated explants to the infection was observed. This indicates that the placentas displayed a constitutive immunity against the viruses. To study the role of endogenous cytokines in antiviral immunity, we added specific antibodies neutralizing IFN and TNF activities to VSV-infected OC and checked their influence on viral replication. Increases of 10-fold to 100-fold of VSV replication in the OC treated with anti-TNF-alpha, anti-IFN-alpha, anti-IFN-gamma or anti-IFN-beta sera were observed. The results indicate the importance of the endogenous cytokines in placental and amniotic membrane immunity. However, we did not observe a simple correlation between the spontaneous IFN and TNF production and the level of resistance against viruses. In view of the results, the participation of TNF and IFN in the constitutively expressed immunity of human placenta is of a more complex nature.
 ...
PMID:Antiviral nonspecific immunity of human placenta at term: possible role of endogenous tumor necrosis factors and interferons. 893 70

Studies of hamster-human and mouse-human somatic fibroblast hybrids and transfected mouse fibroblasts have demonstrated that signaling through the human interferon-gamma receptor (hu-IFN-gammaR) requires the formation of a complex consisting of ligand (IFN-gamma), a ligand binding receptor chain (IFN-gammaR1), and a signal transducing receptor chain (IFN-gammaR2). To date, the ability of this receptor complex to transduce the full repertoire of biological signals has been difficult to assess due to the limited number of activities that IFN-gamma can exert on fibroblasts. The current report assesses the ability of hu-IFN-gammaR chains to transduce signals in the absence of background human gene products by expressing hu-IFN-gammaR2 in a transformed macrophage cell line (F10/96) derived from a hu-IFN-gammaR1 transgenic mouse. Our results indicate that F10/96 clones expressing both human receptor proteins bind hu-IFN-gamma with an affinity comparable to that of human cells. Binding of either human or mouse IFN-gamma to its respective receptor elicits classic IFN-gamma responses such as up-regulation of major histocompatibility complex antigens, enhanced expression of IRF-1, and increased production of NO2- radicals, interleukin-6, tumor necrosis factor-alpha, and granulocyte macrophage-colony stimulating factor. However, hu-IFN-gamma could not fully protect the clones from cytopathic effects of encephalomyocarditis virus and vesicular stomatitis virus while mo-IFN-gamma could. These results demonstrate that while co-expression of hu-IFN-gammaR1 and hu-IFN-gammaR2 is necessary and sufficient for most IFN-gamma-induced responses, it is not sufficient to confer a generalized antiviral state. These findings further suggest that additional species-specific accessory factor(s) are necessary for full signaling potential through the IFN-gamma receptor complex. The nature and potential role of such factors in IFN-gammaR signaling is discussed.
 ...
PMID:Mouse macrophages carrying both subunits of the human interferon-gamma (IFN-gamma) receptor respond to human IFN-gamma but do not acquire full protection against viral cytopathic effect. 895 96


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>