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)

Inhibitory effects of nitric oxide (NO) on vesicular stomatitis virus (VSV) infection were investigated by using a VSV-susceptible mouse neuroblastoma cell line, NB41A3. Productive VSV infection of NB41A3 cells was significantly inhibited by an organic NO donor, S-nitro-N-acetylpenicillamine (SNAP), while the control compound N-acetylpenicillamine (NAP) had no effect. Survival rate of VSV-infected cells was greatly increased by the treatment with SNAP, while the NAP treatment did not have any effect. Adding SNAP 30 min prior to infection resulted in complete inhibition of viral production when a low multiplicity of infection (MOI) was used. Substantial inhibition of viral production was also obtained with treating cells 6 h earlier before infection with a higher MOI. Activating the neuronal NO synthase by treating cells with N-methyl-D-aspartate (NMDA) led to significant inhibition of viral production by cells infected at the three doses of virus tested (MOIs of 0.1, 1, and 5). The inhibitory effect of NMDA on viral infection was totally blocked by the NO synthase inhibitor N-methyl-L-arginine. However, adding hemoglobin, a strong NO-binding protein and thus an inactivator of NO activity, did not reverse the NMDA-induced inhibition of viral production, suggesting that NO might exert its antiviral effects inside the NO-producing cells. Collectively, these data support the anti-VSV effects of NO, which might be one of the important factors of natural immunity in controlling the initial stages of VSV infection in the central nervous system.
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PMID:Inhibition of vesicular stomatitis virus infection by nitric oxide. 753 52

In this report, the kinetics of cellular inflammatory changes in the brain of vesicular stomatitis virus (VSV)-infected C57BL/6 (B6) mice was determined. The behavior and survival rate of infected B6 were carefully monitored each day. Infectious viral titers and VSV antigen distribution were determined at several time points during the course of infection. Strong activation of both astrocytes and microglia was observed after VSV infection. Induction of type II nitric oxide synthase (iNOS) was detected in activated microglia in the olfactory bulb (OB) starting at day 4 postinfection. Induced expression of major histocompatibility complex (MHC) molecules and rapid infiltration of both T cells and natural killer (NK) cells were detected in the VSV-infected CNS. Collectively, these data indicate that the response to CNS infection in B6 mice, which is often primarily Th1 in characteristics, is comparable to BALB/c mice, a strain that often shows a Th2-dominated immune response.
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PMID:Host immune response to vesicular stomatitis virus infection of the central nervous system in C57BL/6 mice. 889 Apr 78

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 antiviral effects of nitric oxide (NO) on Japanese encephalitis virus (JEV), a member of the family Flaviviridae, were investigated in this study. In vitro, inhibition of replication of JEV in gamma interferon-activated RAW 264.7 murine macrophages was correlated to cellular NO production. When cocultured with infected murine neuroblastoma N18 cells, gamma interferon-activated RAW 264.7 cells also efficiently hindered JEV replication in contiguous bystanders, and this anti-JEV effect could be reversed by an NO synthase (NOS) inhibitor, N-monomethyl-L-arginine acetate. In vivo, the mortality rate increased as the NOS activity of JEV-infected mice was inhibited by its competitive inhibitor, N-nitro-L-arginine methyl ester. Moreover, when an organic donor, S-nitro-N-acetylpenicillamine (SNAP), was used, the NO-mediated antiviral effect was also observed in primarily JEV-infected N18, human neuronal NT-2, and BHK-21 cells, as well as in persistently JEV-infected C2-2 cells. These data reaffirm that NO has an effective and broad-spectrum antimicrobial activity against diversified intracellular pathogens. Interestingly, the antiviral effect of NO was not enhanced by treatment of N18 cells with SNAP prior to JEV infection, a measure which has been shown to greatly increase the antiviral effect of NO in infection by vesicular stomatitis virus. From biochemical analysis of the impact of NO on JEV replication in cell culture, NO was found to profoundly inhibit viral RNA synthesis, viral protein accumulation, and virus release from infected cells. The results herein thus suggest that NO may play a crucial role in the innate immunity of the host to restrict the initial stage of JEV infection in the central nervous system.
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PMID:Inhibition of Japanese encephalitis virus infection by nitric oxide: antiviral effect of nitric oxide on RNA virus replication. 918 90

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

The role of nitric oxide synthase (NOS) in host defense and clearance of vesicular stomatitis virus (VSV) from the central nervous system (CNS) was examined. NOS-1, NOS-2, and NOS-3 knockout mice were infected with VSV and were treated with either IL-12 or medium. IL-12 treatment resulted in substantially decreased VSV titers in wildtype and NOS-3 knockout mice, but had a marginal effect in the NOS-1 and NOS-2 knockout mice. NOS-1 expression in neurons was associated with survival from VSV infection. The data indicate that the enzyme activity is local, since NOS-2 expression in microglia and inflammatory macrophages and NOS-3 expression in astrocytes, endothelial cells, and ependymal cells did not compensate.
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PMID:Neuronal expression of NOS-1 is required for host recovery from viral encephalitis. 1036 76

In this report, the role of nitric oxide synthase (NOS) and IL-12 administration in inhibition of vesicular stomatitis virus (VSV) from infected neuroblastoma cells was examined. We previously have shown that cytokine treatment of cells results in the induction of NOS-1, and this is associated with a 2 log inhibition of VSV production. We performed these studies to examine the mechanism by which viral replication is suppressed. Neuroblastoma cells (NB41A3) were treated with either IL-12 or medium and subsequently infected with VSV. Viral protein and mRNA were isolated from these cells, and their levels were measured by Western or Northern blots, respectively. mRNA levels were decreased modestly, but viral proteins were decreased substantially in cells pretreated with IL-12, suggesting that the inhibitory effect of NO is working at the translational level. Cytokine treatment of cells was not associated with oxidative stress. The viral proteins also were nitrosylated. These data suggest that the mechanism of NO inhibition of viral replication occurs through translational interference and posttranslational modifications of viral components.
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PMID:Mechanisms of cytokine-mediated inhibition of viral replication. 1038 58

Intranasal infection of mice by Vesicular Stomatitis Virus (VSV) often leads to breakdown of the blood-brain barrier (BBB). The role of Interleukin 12 (IL-12) and nitric oxide synthase (NOS) was examined here. Wild-type (WT), NOS-1 knockout (KO), and NOS-3 KO mice were infected with VSV and treated with either IL-12 or medium. IL-12 treatment of uninfected hosts did not result in pathology. In contrast with WT and NOS-1 KO mice, where extensive gross and ultrastructural correlation of BBB breakdown were evident following infection, in NOS-3 KO mice, integrity of the BBB was observed. Thus NOS-3 activity in astrocytes, endothelial cells, or ependymal cells may play an essential role in regulating the BBB.
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PMID:Regulation of the BBB during viral encephalitis: roles of IL-12 and NOS. 1044 72

Skin lesions are common manifestations of zinc deficiency in humans and animals, but the pathogenic mechanisms have not been fully clarified. In the present study, a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), was given to zinc-deficient (ZD) rats to see whether it prevents or delays the occurrence of skin lesions. Weanling male rats were given free access to a ZD diet (2 mg zinc/kg) for 4 wk to induce zinc deficiency. Control rats, including pair-fed (PF) and ad libitum (AL) groups, were given a diet supplemented with zinc (50.8 mg zinc/kg. L-NAME (0.3 g/L in drinking water) was given to some ZD rats for 3 wk, starting at the second week of their ZD dieting. Dermatitis of the extremities, balanitis, stomatitis, and alopecia appeared in ZD but not in AL and PF rats. Administration of L-NAME significantly reduced the frequency of cutaneous and mucocutaneous inflammatory lesions but did not prevent alopecia in the ZD rats. Reverse transcription polymerase chain reaction showed that inducible nitric oxide synthase mRNA was expressed in the paw skin of ZD but not of AL and PF rats. Evaluation of skin microvascular permeability by the Evans blue leakage technique indicated that L-NAME administration significantly attenuated extravasation of Evans blue in the paw skin of ZD rats. Furthermore, stains positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling were condensed and diffusely distributed over the epidermis, dermis, and subcutaneous tissue of paws in ZD rats. ZD rats had intense cell infiltration and parakeratosis in the paw skin. L-NAME administration effectively prevented these morphologic changes. These results demonstrate that nitric oxide synthase inhibitor ameliorates inflammatory lesions of the skin in ZD rats.
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PMID:Nitric oxide synthase inhibitor attenuates inflammatory lesions in the skin of zinc-deficient rats. 1067 33

Cyclooxygenase (COX) is the key enzyme in the conversion of arachidonic acid to prostaglandins. COX has two isoforms: COX-1, the constitutively expressed form, and COX-2, the inducible form. Prostaglandins are mediators of many critical physiological and inflammatory responses, but little is known about their roles during a viral infection in the central nervous system (CNS). We used non-selective inhibitors of COX, aspirin and indomethacin, and a selective antagonist of COX-2, celecoxib, to study the role of prostaglandins in Vesicular Stomatitis Virus (VSV) induced encephalitis. We found that the inhibition of COX antagonizes VSV propagation both in vitro and in vivo. In addition, aspirin and celecoxib both prevented the disruption of the blood brain barrier in VSV-infected mice. In vitro experiments showed that the effect of COX inhibition was at least partially mediated by increased production of Nitric Oxide (NO), a molecule known to inhibit VSV replication. When NO production was inhibited by N(omega)-nitro-L-methyl-arginine-ester (L-NAME), a nitric oxide synthase (NOS) inhibitor, the difference in viral titer between aspirin (or celecoxib)-treated and the control cells was abolished. VSV-infected mice treated with celecoxib expressed more NOS-1 and produced more NO in their CNS compared to the controls. Our data suggest that the product(s) of COX have antagonistic effect(s) on NO production in the mouse CNS.
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PMID:NSAID treatment suppresses VSV propagation in mouse CNS. 1102 93


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