Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Indoleamine 2,3-dioxygenase (IDO) and nitric oxide synthase (NOS) type II are induced in macrophages by interferon (IFN)-gamma and lipopolysaccharide (LPS). Nitric oxide has been previously shown to inhibit IDO activity. We studied whether metabolites of tryptophan via the IDO pathway could alter NOS II activity. In RAW 264.7 cells, the phenolic antioxidant 3-hydroxyanthranilic acid (OH-AA), but not anthranilic acid, inhibited citrulline synthesis by NOS II at sub-millimolar concentrations, when added 1 h before IFN-gamma and LPS. OH-AA inhibited NOS II activity in cytosolic extracts, suggesting a direct action of OH-AA on NOS II protein. Moreover, expression of NOS II mRNA and activation of the nuclear factor kappa B (NF-kappa B) in RAW 264.7 cells were decreased by a pretreatment with OH-AA, but not anthranilic acid, before addition of IFN-gamma and LPS. This pretreatment also inhibited activation of NF-kappa B in response to TNF-alpha in lymphoblastoid J.Jhan5-1 cells. Finally, expression of a long terminal repeat of the human immunodeficiency virus (HIV-LTR)-driven luciferase reporter gene, controlled by NF-kappa B activation, was severely decreased by OH-AA or 3-hydroxykynurenine in J.Jhan5-1 cells. Other tryptophan derivatives were inactive. These data identify OH-AA as an aminophenolic tryptophan derivative inhibiting NF-kappa B activation and impairing both NOS II expression and activity in a millimolar concentration range.
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PMID:Inhibition of nitric oxide synthase expression and activity in macrophages by 3-hydroxyanthranilic acid, a tryptophan metabolite. 912 84

The immunomodulatory properties of (R)-enantiomer of 9-(2-phoshonomethoxypropyl)adenine ((R)-PMPA), one of the most potent acyclic nucleotide analogs effective against human immunodeficiency virus (HIV), were investigated under in vitro conditions using murine peritoneal macrophages. Remaining without influence on interferon-gamma and interleukin-2 expression, (R)-PMPA dramatically stimulated in a concentration- and time-dependent manner the secretion of tumor necrosis factor alpha (TNF-alpha) and interleukin-10. It also substantially augmented the production of nitric oxide (NO) induced by exogenous interferon-gamma. Inhibitory experiments using neutralizing antibodies against TNF-alpha and/or interleukin-10 demonstrated that these two cytokines are major factors responsible for triggering the underlying mechanism(s) leading to enhanced NO production. The novel findings on the immunomodulatory potential of acyclic nucleotide analogs are discussed in the context of their possible implication in antiviral therapeutic efficacy.
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PMID:Antiretroviral agent (R)-9-(2-phosphonomethoxypropyl)adenine stimulates cytokine and nitric oxide production. 927 86

Recombinant viruses have been investigated as candidate vaccines, and have also been used extensively as immunological tools. Recent advances in this area include the following: the construction and testing of a recombinant simian immunodeficiency virus encoding human interferon-gamma; the development of new vectors such as recombinant poliovirus; and the generation of polyepitope vaccines. Basic immunological research has benefited from the use of recombinant viruses to further understand the role of molecules such as CD40 ligand, nitric oxide and interleukin-4.
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PMID:Recombinant viruses as vaccines and immunological tools. 928 82

BACKGROUND-MATERIALS: Mice with normal or impaired immune function were studied for responses to intranasal infection with MHV68, a gammaherpesvirus that acutely infects lung epithelial cells and establishes latency in B cells. Infection of normal mice induced a vigorous pulmonary inflammatory response composed of T, B, and NK cells and macrophages and stimulated activation and proliferation of T and B cells in spleen. METHODS-RESULTS-CONCLUSIONS: Resolution of the infection was associated with induction of MHV68-specific antibodies, but virus-specific cytotoxic T cells were not detected. Mice inoculated with retroviruses that induce severe immunodeficiency unexpectedly cleared MHV68 from lung in the same time-frame as controls and failed to develop latency as determined by infectious center tests of spleen cells. In contrast, control of MHV68 infection in spleen and/or lung was impaired in mice deficient in CD4+ or CD8+ T cells or both T cell subsets, B cells, IFN-gamma, or inducible nitric oxide synthase (iNOS). Infection was uniformly lethal in nude and iNOS-deficient mice and killed one-third of IFN-gamma-deficient mice. These results indicate that resistance to MHV68 is markedly influenced by expression of IFN-gamma from T cells leading to induction of iNOS and generation of nitric oxide.
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PMID:Characteristics of a murine gammaherpesvirus infection immunocompromised mice. 929 94

In the human lymphoblastoid T cell line JJhan-5.1, stably transfected with a human immunodeficiency virus-1 long terminal repeat luciferase vector, the level of luciferase activity is dependent on activation of the nuclear factor kappaB (NF-kappaB) transcription factor. Tumor necrosis factor-induced luciferase activity was not modified in JJhan-5.1 cells co-cultivated with murine adenocarcinoma EMT-6 cells but was strongly decreased when nitric oxide (NO) synthase 2 expression was induced in these cells. Two NO synthase inhibitors counteracted this inhibitory effect. Tumor necrosis factor-alpha binding to JJhan-5.1 cells was not modified after incubation with EMT-6 cells. Viability and protein synthesis in JJhan-5.1 cells were also unchanged. Induction of NF-kappaB DNA binding activity was inhibited when EMT-6 cells expressed NO synthase 2 activity. Aminoguanidine, which completely abolished nitrite production, prevented this inhibition. NF-kappaB activation was also strongly inhibited by S-nitrosoglutathione but was marginally affected by N-(2-aminoethyl)-N-(2-hydroxy-2-nitrosohydrazino)-1, 2-ethylenediamine. Taken together, these results indicated that NO-related species, released by EMT-6 effector cells and probably different from NO itself, inhibited NF-kappaB activation in human lymphoblastoid target cells. Consequently, transcriptional activity of a long terminal repeat-driven luciferase gene construct was markedly diminished.
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PMID:Inhibition of NF-kappaB and HIV-1 long terminal repeat transcriptional activation by inducible nitric oxide synthase 2 activity. 946 73

Nitric oxide (NO) has been implicated in certain immunopathogenetic mechanisms during the course of infection with human immunodeficiency virus (HIV). We have evaluated the levels of NO release and lymphocyte apoptosis in peripheral blood mononuclear cell (PBMC) cultures from HIV-1 infected subjects and healthy controls. We have also examined these 2 parameters in parallel cultures maintained under conditions where either NO synthesis was inhibited or high level of NO was present. Nitrite contents in culture supernatants were measured as the stable end products of the released NO. Levels of spontaneous apoptosis and activation-induced cell death (AICD) by anti-CD3 or by phytohemagglutinin were evaluated using flow cytometry. Additional experiments were also aimed at addressing a potential link between NO synthesis and HIV-1 replication in human monocyte-derived macrophages (MDMs). Acutely infected MDMs with HIV-1Bal were maintained in culture, without any additional activation signal, for a period of 14 days. Nitrites in the supernatants and mRNA accumulation of the inducible NO synthase (iNOS) in infected cells were assessed over the whole culture period. In addition, the effect of blocking NO synthesis during and after infection of MDMs, using an inhibitor of NO, was evaluated on the level of viral replication as measured by the presence of P24 antigen in the supernatants. Similarly, the effect on HIV replication of high NO levels in MDM cultures, supplied by a donor of NO during the 24 h period of infection, was also studied. We conclude that no elevation in NO release could be detected in PBMC cultures from HIV-1 infected subjects and that modulation of NO content may slightly regulate the level of spontaneous lymphocyte apoptosis but not that of AICD. Infection of MDMs with HIV-1 does not seem to induce detectable NO release or iNOS mRNA accumulation. Similarly, neither inhibition of NO synthesis nor the presence of high NO levels during the infection period could modify the outcome of virus replication in macrophages.
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PMID:Role of nitric oxide in the regulation of lymphocyte apoptosis and HIV-1 replication. 956 43

During HIV1 infection, nitric oxide (NO) could significantly contribute to immune dysregulation by its multiple effects on the modulation of the host immune response. The in vivo regulation of NO production is attributable to several nitric oxide synthases, one of which is a cytokine-inducible enzyme (iNOS). In vitro experiments suggest that iNOS expression in macrophages may be directly modulated by HIV infection. Acute infection of macaques with a pathogenic strain of the simian immunodeficiency virus (SIV) represents a relevant animal model for the in vivo study of the relationships between iNOS expression and lentiviral replication. Indeed, acute infection in this model is characterized by high rates of viral replication associated with early cytokine dysregulations, in the absence of opportunistic infection. In our experiment, two cynomolgus macaques were inoculated intravenously with a pathogenic isolate of SIVmac251, and iNOS gene expression was investigated ex vivo during acute infection in mononuclear cells obtained from bronchoalveolar lavage (BALMCs). An enhancement of this gene expression was observed as early as the second week of infection, at the time of peak of systemic viraemia, and increased until day 31 p.i. This overexpression was concomitant with a marked linear increase in IFN gamma expression in BALMCs. At the time of systemic viral load peak, the production of NO in plasma of these two monkeys was evidenced by the detection of large amounts of nitrate.
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PMID:Nitric oxide synthesis during acute SIV mac251 infection of macaques. 960 2

Acute exposure of human saphenous vein or internal thoracic artery endothelium to either morphine [27.4 +/- 3.7 and 35.4 +/- 4.1 nM nitric oxide (NO), respectively] or anandamide (18.3 +/- 2.2 and 24.3 +/- 3.0 nM, respectively) results in NO release, whereas exposure to the human immunodeficiency virus envelope protein gp120 does not. After the short-term exposure of the vessel endothelium, monocyte adherence is diminished with morphine and anandamide treatment (jointly by -80%), whereas it is enhanced with that of gp120 (approximately 40%), indicating that gp120 enhances the ability of the endothelium to adhere monocytes. Long-term or continuous exposure of the endothelia to all agents results in a significant enhancement of monocyte adherence (p < 0.05), which is further increased when exposed to either morphine and anandamide plus gp120. This is caused by a desensitization of the endothelium to further NO release after the initial exposure to either anandamide or morphine. The results serve to indicate that in individuals abusing opiates and or cannabinoids, a tissue [i.e., central nervous system (CNS)] viral load may be higher, and acquired immunodeficiency syndrome (AIDS) may progress more rapidly because monocyte adherence and mobility is significantly increased, indicating a higher level of transmembrane migration.
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PMID:Long-term exposure of human blood vessels to HIV gp120, morphine, and anandamide increases endothelial adhesion of monocytes: uncoupling of nitric oxide release. 964 70

Monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients had a defect in their ability to kill Rhodococeus equi in vitro, as compared with healthy HIV-seronegative individuals. Virulent and avirulent R. equi strains isolated from humans and horses showed no significant intracellular replicative differences within both HIV-positive and -negative monocytes/macrophages. Infection with R. equi induced the production of nitric oxide (NO) by monocytes/macrophages from healthy individuals, but not by cells from HIV-positive patients. The NO formation was significantly inhibited by L-NG-monomethyl arginine and arginase. However. neither competitive inhibition of NO synthesis from L-arginine with L-NMMA nor depletion of arginine with arginase altered the killing activity of human monocytes/macrophages against R. equi, thus suggesting that L-arginine:NO pathway is not required for the intracellular antirhodococcal mechanisms of human monocytes/macrophages.
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PMID:Rhodococcus equi infection of monocytes/macrophages from human immunodeficiency virus (HIV)-infected patients and healthy individuals: evaluation of intracellular killing and nitric oxide production. 965 16

Immunodeficiency follows extensive burns. We investigated some underlying mechanisms in rats, 10 days after a full-thickness skin burn affecting 20% of total body surface area. In both normal and burned rats the splenocyte proliferative response to Con A was linearly and negatively correlated with nitric oxide (NO) production. In all burned rats, the proliferative response was depressed by more than 80% and NO production corresponded to a nitrite concentration above 20 microM. Proliferative responses in burned rats were fully restored in the presence of 250 microM NG-monomethyl-L-arginine (NMMA). A time course study of NO production in response to Con A, LPS, anti-CD3, and IFN-gamma showed that splenic macrophages from burned rats responded to direct and indirect stimuli more rapidly and more intensively than normal macrophages. In the second part of this work, the effect of the overproduction of NO on the synthesis of immunoregulatory and proinflammatory cytokines was investigated. Although it was inhibited, IFN-gamma production by splenocytes from burned rats remained sufficient for NO synthase induction and was restored by NMMA. Concomitantly, IL-2 concentration was enhanced but returned to normal in the presence of NMMA. TNF production was halved after burn injury and NMMA partially restored it. In contrast, IL-6 production was enhanced and increased further in the presence of NMMA. Therefore, cytokines were differently affected by burn injury and variously regulated by NO.
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PMID:Role of nitric oxide in depressed lymphoproliferative responses and altered cytokine production following thermal injury in rats. 966 54


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