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 have previously shown that the antiviral state of explanted mouse peritoneal macrophages (PM) decays during in vitro culture and that this decay is much more rapid in Lpsd PM than it is in Lpsn PM. Moreover, Lpsn PM can transfer the antiviral state to other cells, whereas Lpsd PM cannot. In vitro treatment of Lpsn PM with different agents [i.e., bacterial lipopolysaccharide (LPS), interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha, macrophage colony-stimulating factor (M-CSF) and antibody to Mac-1 antigen] induced an antiviral state to vesicular stomatitis virus (VSV) which was inhibited by antibodies to IFN-beta. Treatment of Lpsn PM with LPS or IFN-gamma resulted in greater accumulation of IFN-beta mRNA, whereas no change in the barely detectable levels of IFN-alpha mRNA was observed. Marked accumulation of IFN-beta mRNA was also observed in PM after TNF-alpha treatment. M-CSF and IFN-gamma (but not LPS) also induced an IFN-mediated antiviral state in Lpsd PM. Low levels of spontaneous transcription of IFN-beta mRNA were detected in nuclei from Lpsd PM. Treatment of Lpsd PM with IFN-gamma for 3 h resulted in the accumulation of IFN-beta mRNA without any concomitant increase in the transcription of the IFN-beta gene, as determined by run-on transcription assays with isolated nuclei. The addition of as little as I international unit/ml of IFN-gamma to PM resulted in a 100-fold inhibition of VSV yield. As antibodies to IFN-alpha/beta inhibited only a portion of the IFN-gamma-induced antiviral state, such an antiviral state might reflect the synergism between IFN-gamma and endogenous IFN-beta. In fact, the addition of low doses of both IFN-gamma and IFN-beta to either Lpsn or Lpsd PM resulted in synergistic antiviral effects. In vivo treatment of Lpsd mice with granulocyte-macrophage (GM)-CSF, M-CSF, IFN-gamma or Newcastle disease virus rendered peritoneal cells capable of transferring an antiviral state. These results indicate that (i) various stimuli can induce IFN-beta production by PM, (ii) Lpsd PM spontaneously transcribe low levels of IFN-beta mRNA, even though they cannot transfer an antiviral state, (iii) different stimuli, but not LPS, induce a normal IFN response in Lpsd PM, (iv) IFN-gamma increases the accumulation of IFN-beta mRNA in Lpsd PM by post-transcriptional mechanisms and (v) IFN-gamma may act synergistically with endogenous IFN-beta in inducing a potent antiviral state to VSV in PM.
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PMID:Effects of different biological response modifiers on interferon expression in bacterial lipopolysaccharide (LPS)-responsive and LPS-hyporesponsive mouse peritoneal macrophages. 170 75

T cell-mediated protection against a recombinant vaccinia virus was evaluated in mice with respect to the relative contributions of CTL vs that of T cell-dependent IL and of CD4+ cells. H-2b mice primed with the wildtype of vesicular stomatitis virus serotype Indiana (VSV-IND wt) mount an in vitro measurable cytotoxic response against the nucleoprotein (NP) of VSV-IND and are protected against a challenge infection with a vaccinia-VSV recombinant virus expressing the NP of VSV-IND (vacc-IND-NP). Their protective mechanism was highly susceptible to in vivo depletion of CD8+ T cells, but resistant to CD4+ depletion or treatment with anti-IFN-gamma and anti-TNF-alpha. Surprisingly, also VSV-CTL nonresponder H-2k mice were protected against a challenging infection with vacc-IND-NP when primed with VSV-IND wt. In contrast to the CTL responder H-2b mice, this protection was highly susceptible to CD4+ T cell depletion and to anti-IFN-gamma or anti-TNF-alpha treatment, but resistant to CD8+ T cell depletion. Antibodies were not responsible because they failed to transfer protection; in contrast CD4+ T cells conferred significant protection. VSV-CTL responder H-2b and nonresponder H-2k mice were protected almost equally well against a challenge dose of 10(3) pfu vacc-IND-NP inoculated intracerebrally. However, after intracerebral challenge with 5 x 10(6) pfu vacc-IND-NP, the CTL nonresponder mice died, whereas the CTL responder mice eliminated the virus by day 5. These results collectively show that CD4+ T cell-dependent IL may mediate antiviral protection, but their efficiency is relatively weak compared with CD8-mediated protection correlating with cytotoxic activity in vitro.
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PMID:Antiviral protection by CD8+ versus CD4+ T cells. CD8+ T cells correlating with cytotoxic activity in vitro are more efficient in antivaccinia virus protection than CD4-dependent IL. 171 Feb 46

Human PBMC from HIV-1-infected individuals produced ex vivo in response to vesicular stomatitis virus only low amounts of IFN-alpha. This impairment was significant as early as Walter Reed (WR) stage 2; at WR stage 4-5, the production was almost zero. At WR stage 2 of infection, IFN-alpha mRNA was exclusively found in association with polyribosomes, indicating that IFN-alpha gene was transcriptionally inactive under the experimental conditions used. A similar decrease of the level of transcripts as a function of the progression of the disease was also observed for the IFN-gamma mRNA. In contrast, TNF-alpha production was strongly enhanced in PBMC from HIV-1-infected individuals after stimulation with LPS compared to the TNF-alpha production of activated PBMC from healthy donors. Almost parallel with the increase of the level of the transcript for TNF-alpha, the level of TNF-beta increases as well. Data are presented which show that the increased TNF-alpha production is due to a longer half-life of TNF-alpha transcripts in PBMC from infected individuals. These results let us suggest that the up-regulation of TNF-alpha gene expression in PBMC from HIV-infected individuals is controlled predominantly on the posttranscriptional level, whereas transcriptional events regulate the level of IFN-alpha transcripts. This assumption is supported by run-on experiments which revealed that the extent of transcription of TNF-alpha gene is almost identical in nuclei from stimulated PBMC of noninfected and HIV-infected donors, whereas the transcription of IFN-alpha gene is strongly suppressed in nuclei from HIV-infected individuals at WR stages 3 and 6.
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PMID:Differential gene expression of IFN-alpha and tumor necrosis factor-alpha in peripheral blood mononuclear cells from patients with AIDS related complex and AIDS. 229 23

The secretory (tumor necrosis factor, TNF-alpha; nitrite) and cellular response (mitochondrial respiration, TNF-alpha-independent tumoricidal activity) of a pure, lymphocyte-free population of resting, unprimed rat bone marrow-derived mononuclear phagocytes (BMM phi) to direct interaction with viruses, protozoa, and fungi was assessed and compared with that triggered by bacterial agents and interferon-gamma (IFN-gamma). Viruses (herpes simplex, vaccinia, poliomyelitis, vesicular stomatitis, lymphocytic choriomeningitis, Sendai), protozoa (Trypanosoma brucei, Giardia lamblia), and fungi (Penicillium, Trichosporon, Fusarium, Rhizopus, Aspergillus, Geotrichum species) affected primarily the secretion of TNF-alpha and mitochondrial respiration of BMM phi; their effects on the secretion of nitrite and on tumoricidal activity were at best marginal. Collectively, the macrophage response to viruses, protozoa, and fungi was less varied and less marked than that to bacterial agents (intact organisms, peptidoglycan, lipoteichoic acid, lipopolysaccharide) and IFN-gamma.
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PMID:Macrophage response to viruses, protozoa, and fungi: secretory and cellular activities induced in resting unprimed bone marrow-derived mononuclear phagocytes. 799 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.
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PMID:T cell-dependent IFN-gamma exerts an antiviral effect in the central nervous system but not in peripheral solid organs. 845 Feb 14

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.
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PMID:Antiviral nonspecific immunity of human placenta at term: possible role of endogenous tumor necrosis factors and interferons. 893 70

In this report, the role of IFN-gamma in host defense to exogenous IL-12 and clearance of vesicular stomatitis virus (VSV) from the central nervous system was examined. Wild-type and IFN-gamma knockout mice infected with VSV were treated with IL-12 or medium. In both groups, IL-12 treatment resulted in 1) substantially decreased VSV titers in brain homogenates and diminished immunohistochemical detection of VSV Ags in tissue sections; 2) induction of types 1, 2, and 3 nitric oxide synthase; and 3) induction of MHC molecules and rapid infiltration of both T cells and NK cells. These results suggest that IFN-gamma production, both systemically and in the olfactory bulb, contributes to but is not essential for clearance of VSV from the brain. Neutralization of TNF-alpha in IFN-gamma knockout mice mice treated with IL-12 was accompanied by the same immunohistochemical changes, implying that neither IFN-gamma nor TNF-alpha was required. In vitro studies using purified IL-12 or IFN-gamma in culture medium induced nitric oxide synthase isoforms in neurons, glia, and macrophages, and MHC II on glia and macrophages. These data suggest that IL-12 directly activates neurons to promote viral clearance in vivo.
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PMID:IFN-gamma is not required in the IL-12 response to vesicular stomatitis virus infection of the olfactory bulb. 931 43

To investigate the physiological role of IL-12 in viral infections in terms of T cell cytokine responses involved in virus-specific Ig isotype induction and in antiviral protection, immune responses elicited upon infection of IL-12-deficient mice with lymphocytic choriomeningitis virus (LCMV) or vesicular stomatitis virus (VSV) were studied. Infection of IL-12-deficient mice with LCMV induced a virus-specific type 1 cytokine response as determined by in vitro cytokine secretion patterns as well as by in vivo intracellular cytokine staining of LCMV-specific CD4+ TCR transgenic T cells that had clonally expanded in LCMV-infected IL-12-deficient recipient mice. In addition, LCMV- and VSV-specific IgG responses exhibited normal serum IgG2a/IgG1 ratios, demonstrating again virus-specific CD4+ T cell induction of type 1 phenotype in IL-12-deficient mice upon viral infection. LCMV and VSV immune mice were found to be protected against challenge immunization with recombinant vaccinia viruses expressing either the LCMV- or the VSV-derived glycoprotein, respectively. This protection is known to be mediated by T cell-secreted type 1 cytokines IFN-gamma and TNF-alpha. In contrast, IL-12-deficient mice showed impaired abilities to control infection with the facultative intracellular bacterium Listeria monocytogenes at early time points after infection. However, at later time points of infection, IL-12-deficient mice were able to clear infection. These findings may indicate that viruses are able to induce type 1 T cell responses in the absence of IL-12 as opposed to some bacterial or parasitical infections that are crucially dependent on the presence of IL-12 for the induction of type 1 immune responses.
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PMID:IL-12 is not required for induction of type 1 cytokine responses in viral infections. 991 21

The role of soluble receptors for TNF-alpha (sTNF-Rs) as markers of virus-induced host responses was studied by the use of murine model infections. A marked elevation in serum levels of sTNF-R75, but not sTNF-R55, was found 1 day after infection with vesicular stomatitis virus (VSV). In mice infected with lymphocytic choriomeningitis virus (LCMV), an early increase was also revealed, but peak levels of sTNF-R75 were observed later temporally related to maximal T cell-mediated anti-viral activity. Analysing different well characterized knockout mice, it was found that elevated release of sTNF-R75 into serum early after VSV infection was independent of T cells, whereas interferon (IFN)-alpha/beta seemed to be a major mediator. In contrast, increased release of sTNF-R75 into serum 8 days post-LCMV infection was mediated via T cells but independently of both CD40 ligand and IFN-gamma. A simple correlation between release of sTNF-Rs in vivo and macrophage activation in vitro was not present. These findings indicate that sTNF-R75 is indeed a sensitive marker of both innate and specific cell-mediated host reactivity during viral infection, but it is not correlated to a single immunological parameter.
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PMID:Soluble tumour necrosis factor (TNF)-receptor levels in serum as markers of anti-viral host reactivity. 1033 22

IL-15 is a recently identified cytokine that belongs to the four alpha-helix bundle cytokine family and possesses biological activities similar to those of IL-2. Its ability to induce effectors of NK activity suggests its involvement in innate immunity. In this study, we analyzed the effect of different viruses (HSV, EBV, respiratory syncitial virus, vesicular stomatitis virus, influenza virus, reovirus, and Sendai virus) on the up-regulation of NK activity in vitro. Exposure of human PBMC to the these viruses resulted in an immediate up-regulation of NK activity of PBMC via IL-15 induction; this effect was abrogated in the presence of mAbs to IL-15. Results of experiments conducted in parallel using mAbs to IL-15, as well as to other cytokines (IL-2, IL-12, IFN-gamma, and TNF-alpha), clearly indicated that IL-15 was specifically responsible for the observed effect. Furthermore, supernatants of virus-infected PBMC cultures significantly enhanced NK activity of uninfected PBMC in vitro. An increase of IL-15 protein levels 20 h postinfection was also confirmed in a bioassay using the IL-2-dependent cell line CTLL. Kinetic analysis of IL-15 mRNA expression using a semiquantitative RT-PCR revealed that the level of IL-15 messages peaked at different time points (up to 12 h) postinfection, depending on the nature of the virus. Taken together, these results suggest that the IL-15 response of the host to viral infection and the subsequent NK cell activation represent an important effector mechanism of the innate immune surveillance of the host against viral infections.
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PMID:Up-regulation of NK cytotoxic activity via IL-15 induction by different viruses: a comparative study. 1051 Mar 89


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