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)

To investigate the roles of tumor necrosis factor (TNF) and lymphotoxin (LT)-alpha in the development and function of the immune system, the Tnf and Ltalpha genes were simultaneously inactivated in mice by homologous recombination. These mutant mice are highly susceptible to Listeria monocytogenes infection and resistant to endotoxic shock induced by the combined administration of D-galactosamine (D-GaIN) and lipopolysaccharide (LPS). Their splenic microarchitecture is disorganized, characterized by the loss of the clearly defined marginal zone, ill defined T and B cell areas, and absence of MAdCAM-1 and reduced ICAM-1, VCAM-1 and Mac-1 expression. They are devoid of peripheral lymph nodes and Peyer's patches, and show a strong reduction of IgA+ plasma cells in the intestinal lamina propria. The alymphoplasia is accompanied by a marked B lymphocytosis and reduced basal lg levels. Ig depositions in the renal glomerulus and a strong up-regulation of MHC class I antigen expression on endothelial cells of different tissues are observed. The primary humoral immune response towards sheep red blood cells reveals a defective IgG isotype switch, while that against vesicular stomatitis virus is normal. The cytotoxic T cell responses are attenuated, although still effective, against vaccinia, lymphocytic choriomeningitis virus (LCMV-ARM) and LCMV-WE. In conclusion, the combined inactivation of Tnf and Ltalpha confirms their essential role in the normal development and function of the immune system.
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PMID:Multiple immune abnormalities in tumor necrosis factor and lymphotoxin-alpha double-deficient mice. 867 86

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.
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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

Infusion of interleukin-12 (IL-12) enhances recovery from lethal experimental vesicular stomatitis virus (VSV) infection of the central nervous system (CNS). Interleukin-12 treatment resulted in: 1) increased survival frequency; 2) faster recovery from weight loss; 3) substantially decreased VSV titers in brain homogenates and diminished immunohistochemical detection of VSV antigens in tissue sections; 4) earlier and increased CNS expression of types 1, 2, and 3 nitric oxide synthase (NOS) and both major histocompatibility complex (MHC) class I and class II antigens; 5) earlier and increased blood and CNS levels of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma). These results suggest that IL-12 enhances recovery from VSV infection of the CNS.
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PMID:Interleukin-12 promotes recovery from viral encephalitis. 909 30

The interplay between viral infection and lipopolysaccharide (LPS) was studied. Infection with a noncytopathogenic virus, lymphocytic choriomeningitis virus (LCMV), was found to sensitize mice to low doses of LPS. In vivo, this hypersensitivity correlated with hyperproduction of tumor necrosis factor-alpha (TNF-alpha), and in vitro, LPS-stimulated splenic adherent cells produced increased amounts of TNF-alpha. Hyperproduction of TNF-alpha was temporally correlated with virus-induced production of interferon-gamma (IFN-gamma); only marginally increased IFN-gamma and TNF-alpha production was observed in LCMV-infected, T cell-deficient mice and in mice infected with vesicular stomatitis virus, a virus that induces much less T cell activation than does LCMV. Finally, LCMV infection was much less efficient in priming IFN-gamma knockout mice for hyperproduction of TNF-alpha. These findings indicate that clinically silent viral infections may induce hypersensitivity to LPS through T cell activation and subsequent production of IFN-gamma; this sensitizes monocytes/macrophages for hyperproduction of TNF-alpha.
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PMID:Sensitization to lipopolysaccharide in mice with asymptomatic viral infection: role of T cell-dependent production of interferon-gamma. 920 61

We have reported that cultured human umbilical cord vein endothelial cells (HUVEC) differ from endothelium present on vein surface of organ culture (OC) in production of cytokines and susceptibility to viral infections. In this paper we present the effect of viral infections on interferon (IFN), tumor necrosis factor (TNF), and interleukin 6 (IL-6) production in two culture systems: HUVEC and OC. Infection of 24-48 h HUVEC with herpes simplex type 1 (HSV-1) and vesicular stomatitis virus (VSV) reduced the amounts of IL-6 and TNF produced in comparison to those released spontaneously by uninfected cells. No IFN was detected in media from infected and uninfected HUVEC. Limited viral infections of 3-h-HUVEC and OC usually diminished their efficiency of IL-6 and TNF production. In the case of IL-6 synthesis by OC, effect of viral infection depended, however, on the constitutive synthesis of the cytokine. When spontaneous production was high (> 800 U/ml), VSV and HSV-1 infection reduced IL-6 level by 2-50 times; in the case of low production (< 150 U/ml) the stimulation effect (2-4 fold) was observed. OC released spontaneously some IFN activity (2-32 U/ml). HSV-1 infection of OC reduced IFN level, while VSV in single cases slightly upregulated IFN synthesis.
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PMID:Effect of viral infections on the ability of human endothelium for interferon, tumor necrosis factor and interleukin 6 production. 959 94

The multiplication of vesicular stomatitis virus in HeLa cells was inhibited by treating the cells with tumor necrosis factor (TNF). Comparison of the kinetics of virus multiplication and that of virus-induced apoptosis in the TNF-treated cells revealed that the antiviral effect of TNF is accompanied by a rapid induction of apoptosis in the cells upon infection, suggesting that TNF can inhibit virus multiplication by accelerating an apoptotic response in the infected cells.
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PMID:Acceleration of virus-induced apoptosis by tumor necrosis factor. 959 3

A major source of inflammatory cytokines in the measles virus (MV)-infected brain are astrocytes, which produce a variety of soluble mediators including interferons-alpha/beta (IFN-alpha/beta), interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6). Using the MV-strain Edmonston (ED) and the recombinant MV-strain MGV in which the MV-envelope proteins H and F have been replaced by the vesicular stomatitis virus (VSV) envelope protein G, we investigated IL-6 induction in human U-251 astrocytoma cells in the presence and absence of a MV-specific receptor (CD46) interaction. The CD46-MV interaction did not inhibit the induction of cytokines. Similar multiplicities of infection of MGV induced generally lower levels of IL-6 than MV-ED. UV-inactivated replication-incompetent MV-ED induced low levels of IL-6. In contrast, MGV did not induce IL-6 after inactivation with UV light, indicating that the MV-ED-receptor interaction or the uptake of viral particles by membrane fusion induced IL-6, whereas interaction with the VSV-G receptor and uptake of viral particles by endocytosis did not induce IL-6. Crosslink of the MV-receptor CD46 with antibodies and treatment of cells with purified viral glycoproteins led to the induction of small but significant amounts of IL-6. Our data suggest that triggering of CD46 and associated protein kinases can lead to the induction of low levels of IL-6, whereas the replication of the negative strand RNA virus constitutes the major stimulus leading to the synthesis of high levels of IL-6 in astrocytes.
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PMID:Receptor (CD46)- and replication-mediated interleukin-6 induction by measles virus in human astrocytoma cells. 983 49

It is characteristic of viral infections that monocytes/macrophages and lymphocytes infiltrate infected tissue, and neutrophils are absent. CC and non-ELR CXC chemokines predominantly attract mononuclear leukocytes, whereas the ELR motif-expressing CXC chemokines primarily act on neutrophils. To investigate the general role of chemokines in viral diseases, we determined their release and expression patterns after infection of human monocytes with vesicular stomatitis virus (VSV). Human monocytes were productively infected by VSV. Surprisingly, VSV did not induce the release of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and IL-6. In contrast, we found a strong induction of the CC chemokine monocyte chemotactic protein-1 (MCP-1) and the non-ELR CXC chemokine interferon-gamma (IFN-gamma) inducible protein-10 (IP-10) by VSV on the gene and protein level. The expression and release of the neutrophil chemoattractants IL-8 and growth-related oncogene-alpha (GRO-alpha) remained unaffected after VSV infection. Our results indicate that the typical monocyte and lymphocyte-dominated leukocyte infiltration of virus-infected tissue is based on a selective induction of mononuclear leukocyte-attracting chemokines.
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PMID:Selective induction of the monocyte-attracting chemokines MCP-1 and IP-10 in vesicular stomatitis virus-infected human monocytes. 1092 3

It is hypothesized that supernatants from cell cultures contain several factors to modify the human immunodeficiency virus type-1 (HIV-1) infection. Single round infection with pseudotyped viruses with envelope from HIV-1, amphotropic murine leukemia virus (A-MLV) and vesicular stomatitis virus G-protein (VSV-G) carrying luciferase reporter gene detected that not only human T-cell leukemia/lymphoma virus type-I (HTLV-1) transformed cells but also HTLV-I-unrelated T-cells and BJA-B cells released factors enhancing the infection with all pseudotyped viruses in their culture-supernatants. No supernatants upregulated the level of transcription from transfected DNA probe. suggesting that the action of supernatants is different from that of tumor necrosis factor (TNF) and Tax of HTLV-I. These results indicated that factors not always related to HTLV-I were ubiquitously produced and promoted viral infections, probably due to non-specific enhancement of early phase of the infection.
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PMID:Human T-cell leukemia virus type-I (HTLV-I) tax is not the only one factor to enhance human immunodeficiency virus type-I (HIV-1) infection in culture-supernatants. 1155 5

Maternal-infant transmission of human immunodeficiency virus type-1 (HIV-1) is the primary cause of this retrovirus infection in neonates. Trophoblasts have been proposed to play a critical role in modulating virus spread to the fetus. This paper addresses the mechanism of HIV-1 biology in trophoblastic cells. The trophoblastic cell lines BeWo, JAR, and JEG-3 were infected with reporter HIV-1 particles pseudotyped with envelope glycoproteins from the vesicular stomatitis virus or various strains of HIV-1. We demonstrate that despite a high internalization process of HIV-1 and no block in viral production, HIV-1 established a limited infection of trophoblasts with the production of very few progeny viruses. The factor responsible for this restriction to virus replication in such a cellular microenvironment is that the intracellular p24 is concentrated predominantly in endosomal vesicles following HIV-1 entry. HIV-1 transcription and virus production of infectious particles were both augmented upon treatment of trophoblasts with tumor necrosis factor-alpha and interleukin-1. However, the amount of progeny virions released by trophoblasts infected with native HIV-1 virions was so low even in the presence of pro-inflammatory cytokines that a co-culture step with indicator cells was necessary to detect virus production. Collectively these data illustrate for the first time that the natural low permissiveness of trophoblasts to productive HIV-1 infection is because of a restriction in the mode of entry, and such a limitation can be overcome with physiologic doses of tumor necrosis factor-alpha and interleukin-1, which are both expressed by the placenta, in conjunction with cell-cell contact. Considering that there is a linear correlation between viral load and HIV-1 vertical transmission, the environment may thus contribute to the propagation of HIV-1 across the placenta.
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PMID:The low viral production in trophoblastic cells is due to a high endocytic internalization of the human immunodeficiency virus type 1 and can be overcome by the pro-inflammatory cytokines tumor necrosis factor-alpha and interleukin-1. 1260 6


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