Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study was designed to test the effect of bacterial endotoxin on penetration of viruses into the central nervous system (CNS). As a model we used two neurovirulent viruses that lack neuroinvasive capacity: West Nile virus-25 (WN-25) and neuroadapted Sindbis virus (SVN). Administration of lipopolysaccharide (LPS, 100 micrograms/mouse) to CD-1 mice, followed by WN-25 inoculation resulted in 83% encephalitis and death, compared with less than 5% in controls. The results in SVN-inoculated CD-1 mice were quite similar. LPS-treated mice suffered 62% mortality compared with 6% in the nontreated group. No changes in viral neuroinvasiveness were demonstrated in viruses isolated from brains of encephalitic mice, suggesting that neuroinvasion is not due to a selection process for an invasive variant, but to direct penetration of the viruses through the blood-brain barrier (BBB). LPS did not induce WN-25 encephalitis in LPS-insensitive C3H/HeJ mice, compared with 100% neuroinvasion in C3H/HeB mice. Induction of neuroinvasion could be transferred to C3H/HeJ mice by transfusion with serum obtained from LPS-treated, LPS-responsive mice. Passive immunization of CD-1 mice with anti-mTNF antibodies before LPS administration did not prevent LPS-induced WN-25 encephalitis. Furthermore, neutralization of tumor necrosis factor activity in the serum of LPS-treated mice did not abolish its activity, and transfusion-associated encephalitis was observed after the administration of the neutralized serum with WN-25. We suggest that LPS can contribute to virus penetration from the blood into the CNS, a process which turns a mild viral infection into a severe lethal encephalitis. This effect is mediated by soluble factors, and is probably achieved by injury to cerebral microvascular endothelium and modulation of BBB permeability.
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PMID:Viral neuroinvasion and encephalitis induced by lipopolysaccharide and its mediators. 151 38

Caprine arthritis-encephalitis is a retrovirus-induced disease resulting in lymphoproliferative lesions of the CNS and joints. Peripheral blood leukocytes of chronically infected goats were analyzed for the types of cells present and for their reactivity to viral antigen and polyclonal stimulants. Two of 9 infected goats had abnormal numbers of B lymphocytes--one elevated and the other deficient. Lymphocyte reactivity to viral antigens was transiently detectable by a lymphoblastogenic assay in 5 of the 9 goats. The reactive cells were peanut agglutinin-negative T lymphocytes. Concanavalin A induced more division in T lymphocytes of infected goats than in lymphocytes of noninfected goats, whereas the reactions to phytohemagglutinin, pokeweed mitogen, and bacterial lipopolysaccharide were no different in the 2 goat groups. It is concluded that goats infected by the caprine arthritis-encephalitis virus have antigen-reactive T lymphocytes and that infection promotes the response to a nonspecific T-cell stimulant.
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PMID:Augmented T lymphocyte responses and abnormal B lymphocyte numbers in goats chronically infected with the retrovirus causing caprine arthritis-encephalitis. 631 20

Treatment of rats with the dopaminergic ergot alkaloid bromocriptine (BRC) inhibited the following immune reactions: contact sensitivity skin reaction to dinitrochlorobenzene (DNCB); antibody formation to sheep red blood cells and to bacterial lipopolysaccharide; adjuvant arthritis; and experimental allergic encephalitis. Immunosuppressive doses of BRC (5 mg/kg) decreased the serum prolactin (PRL) levels from 84.8 +/- 15.9 ng/ml to 4.9 +/- 1.6 ng/ml. Further studies on DNCB contact sensitivity and on antibody formation revealed that the immunocompetence of BRC-suppressed animals could be restored by additional treatment with either prolactin (PRL) or growth hormone (GH). Treatment with adrenocorticotropic hormone antagonized the restoring effect of PRL and GH. These results suggest that BRC suppressed immunity by its inhibition of PRL, and possibly also by inhibition of GH secretion.
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PMID:Immunomodulation by bromocriptine. 635 9

Activated mouse macrophages can produce high levels of nitric oxide, an antimicrobial effector molecule recently also implicated in antiviral defense. As viral infection may alter macrophage functions, nitric oxide production was investigated in murine macrophages infected with a Flavivirus, tick-borne encephalitis virus. Infected macrophages produced high levels of nitric oxide upon stimulation with lipopolysaccharide without priming, while in control macrophages induction of nitric oxide production by lipopolysaccharide required priming with interferon-gamma. Addition of interferon-gamma to infected macrophages further increased lipopolysaccharide-stimulated nitric oxide production. In contrast, nitric oxide production upon stimulation with interferon-gamma plus tumor necrosis factor-alpha was markedly reduced in infected macrophages. Downregulation of interferon-gamma plus tumor necrosis factor-alpha-induced nitric oxide synthesis by viral infection could be attributed to endogenous interferon-alpha beta produced by infected macrophages. Addition of interferon-alpha beta to uninfected macrophages inhibited interferon-gamma plus tumor necrosis factor-alpha-induced nitric oxide production, and addition of interferon-alpha beta antibodies to infected macrophages increased identically stimulated nitric oxide production to normal levels. Thus, interferon-alpha beta mimicked the effect of viral infection on macrophage nitric oxide production. These findings indicate that viral infection profoundly alters requirements of mouse macrophages for induction of nitric oxide synthesis, depending on the activating signal applied. The described effects of viral infection of macrophages on the regulation of nitric oxide production and new complexity to the role of nitric oxide in host defense against viruses.
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PMID:Viral infection of macrophages profoundly alters requirements for induction of nitric oxide synthesis. 767 26

The effects of caprine arthritis encephalitis virus (CAEV) infection on cytokine activity of caprine monocytes stimulated with Escherichia coli lipopolysaccharide (LPS) were examined. Compared with supernatants from LPS-stimulated monocytes of CAEV-negative goats, supernatants from CAEV-positive goats stimulated less proliferation of murine thymocytes in the MTT (3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide) assay, showed about 50% less IL-1 activity on the IL-1-dependent cell line LBRM-33 1 A-5, and showed about 200% more tumor necrosis factor (TNF) activity on the TNF-sensitive murine fibroblast cell line L-929. These results indicate that CAEV infection changes caprine monocyte cytokine responsivity.
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PMID:Caprine arthritis encephalitis virus infection changes caprine blood monocyte responsiveness to lipopolysaccharide stimulation in vitro. 785 74

Goats infected with caprine arthritis encephalitis virus (CAEV) develop chronic arthritis sharing many features with human rheumatoid arthritis (RA). TNF is thought to be a key mediator contributing to the formation of the arthritic lesion in RA. We studied this cytokine in goats suffering from chronic arthritis. TNF alpha expressing cells were detected by in situ hybridization in synovial membranes of arthritic carpal joints. Expression of TNF alpha did not correlate with the degree of viral replication as assessed by in situ hybridization for viral RNA. In line with the lack of correlation between the degree of viral replication and TNF expression in vivo, we failed to detect increased cytokine RNA in goat macrophages infected with CAE virus in vitro and no TNF protein was found in culture supernatants. In addition, virus infection failed to prime goat macrophages for enhanced TNF expression in response to lipopolysaccharide. Taken together, these findings argue against a direct role of CAE virus in increasing the expression of TNF alpha in caprine arthritis.
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PMID:Expression of TNF alpha in arthritis caused by caprine arthritis encephalitis virus. 898 74

Caprine arthritis encephalitis virus (CAEV) is a lentivirus of goats that leads to chronic mononuclear infiltration of various tissues, in particular, the radiocarpal joints. Cells of the monocyte/macrophage lineage are the major host cells of CAEV in vivo. We have shown that infection of cultured goat macrophages with CAEV results in an alteration of cytokine expression in vitro. Constitutive expression of interleukin 8 (IL-8) and monocyte chemoattractant protein 1 (MCP-1) was increased in infected macrophages, whereas transforming growth factor beta1 (TGF-beta1) mRNA was down-regulated. When macrophages were infected with a CAEV clone lacking the trans-acting nuclear regulatory gene tat, IL-8 and MCP-1 were also increased. No significant differences from cells infected with the wild-type clone were observed, suggesting that Tat is not required for the increased expression of IL-8 and MCP-1 in infected macrophages. Furthermore, infection with CAEV led to an altered pattern of cytokine expression in response to lipopolysaccharide (LPS), heat-killed Listeria monocytogenes plus gamma interferon, or fixed cells of Staphylococcus aureus Cowan I. In infected macrophages, tumor necrosis factor alpha, IL-1beta, IL-6, and IL-12 p40 mRNA expression was reduced in response to all stimuli tested whereas changes in expression of granulocyte-macrophage colony-stimulating factor depended on the stimulating agent. Electrophoretic mobility shift assays demonstrated that, in contrast to effects of human immunodeficiency virus infection of macrophages, CAEV infection had no effect on the level of constitutive nuclear factor-kappaB (NF-kappaB) activity or on the level of LPS-stimulated NF-kappaB activity, suggesting that NF-kappaB is not involved in altered regulation of cytokine expression in CAEV-infected cells. In contrast, activator protein 1 (AP-1) binding activity was decreased in infected macrophages. These data show that CAEV infection may result in a dysregulation of expression of cytokines in macrophages. This finding suggests that CAEV may modulate the accessory functions of infected macrophages and the antiviral immune response in vivo.
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PMID:Caprine arthritis encephalitis virus dysregulates the expression of cytokines in macrophages. 931 28

The response of caprine macrophages to exposure to caprine arthritis-encephalitis virus (CAEV) and lipopolysaccharide (LPS) was investigated in female Nubian and Nubian crossbreed of goats. Macrophages were matured in vitro from monocytes isolated from blood of control and CAEV-infected goats and the concentrations of tumor necrosis factor (TNF-alpha) and interleukin-6 (IL-6) in culture supernatant after exposure of cells to LPS and virus were assayed. Though barely detectable in unstimulated cells, TNF-alpha and IL-6 levels showed peak values of 420 +/- 28 to 530 +/- 32 and 70 +/- 27 to 93 +/- 29, respectively, in supernatants of control goat cells [corrected], remaining high through 24 hrs. post treatment with LPS stimulation. Exposure of these control goat cells [corrected] to virus induced lower secretions (p<0.05) of the cytokines. The peak values occurred between 6 and 12 hrs. post treatment with LPS or virus. Cells prepared from virus-infected goats and treated with the mitogen or virus showed significantly (p<0.05) lower response than those from control goats. The present results suggest a dysregulation, possibly downregulation of the production of both cytokines in macrophages of goats chronically diseased by lentivirus infection.
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PMID:Cytokine production in vitro by macrophages of goats with caprine arthritis-encephalitis. 944 35

Increased mortality has been observed when HIV-infected patients were treated with pyrimethamine (Pyr) as prophylaxis for toxoplasmic encephalitis, suggesting that Pyr might possess immunosuppressive activity. To analyze this in an animal model, immune function was assessed in BALB/c mice using a battery of in vivo and ex vivo assays and an in vivo model of host resistance to Listeria monocytogenes infection. Treatment for 30 days with 60 mg/kg Pyr decreased circulating white blood cell and lymphocyte counts but not neutrophil, red blood cell, or platelet counts or hemoglobin levels. Splenic B cell percentages and lipopolysaccharide-induced B cell proliferation decreased significantly after treatment with 60 mg/kg Pyr, as did levels of anti-keyhole limpet hemocyanin (KLH) IgM in serum 7 days after immunization with KLH. Anti-KLH IgG levels 14 days after immunization were not affected. Percentages of splenic T cells and macrophages and T cell proliferation in the presence of concanavalin A or allogeneic cells were not decreased by Pyr treatment. An ex vivo assay of T-cell-mediated cytotoxicity was also unaffected. When host resistance to L. monocytogenes infection was assessed, dramatic increases in mortality were observed in Pyr-treated compared to control mice. Increased numbers of L. monocytogenes organisms were observed in liver and spleen of Pyr-treated mice, compared to controls. The reduction in Listeria resistance, which is T cell mediated, contrasts with the fact that no significant changes in T-cell-mediated immunity were observed. It is possible that Pyr affects parameters of innate immunity, which were not monitored in this study.
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PMID:Pyrimethamine impairs host resistance to infection with Listeria monocytogenes in BALB/c mice. 957 21

Inflammatory processes contribute to neurodegenerative disease, stroke, encephalitis, and other central nervous system (CNS) disorders. Activated microglia are a source of cytokines and other inflammatory agents within the CNS and it is therefore important to control glial function in order to preserve neural cells. Melanocortin peptides are pro-opiomelanocortin-derived amino acid sequences that include alpha-melanocyte-stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH). These peptides have potent and broad anti-inflammatory effects. We tested effects of alpha-MSH (1-13), alpha-MSH (11-13), and ACTH (1-24) on production of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6), and nitric oxide (NO) in a cultured murine microglial cell line (N9) stimulated with lipopolysaccharide (LPS) plus interferon gamma (IFN-gamma). Melanocortin peptides inhibited production of these cytokines and NO in a concentration-related fashion, probably by increasing intracellular cAMP. When stimulated with LPS + IFN-gamma, microglia increased release of alpha-MSH. Production of TNF-alpha, IL-6, and NO was greater in activated microglia after innmunoneutralization of endogenous alpha-MSH. The results suggest that alpha-MSH is an autocrine factor in microglia. Because melanocortin peptides inhibit production of pro-inflammatory mediators by activated microglia they might be useful in treatment of inflammatory/degenerative brain disorders.
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PMID:Melanocortin peptides inhibit production of proinflammatory cytokines and nitric oxide by activated microglia. 962 Jun 67


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