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)

Pentoxifylline, which inhibits tumor necrosis factor-alpha (TNF alpha), decreases human immunodeficiency virus replication in peripheral blood mononuclear cells. However, TNF alpha is important in cellular defense against M. avium-intracellulare complex (MAC), a common infection in advanced AIDS. The effect of pentoxifylline on mycobacterial colony counts in macrophages with in vivo MAC infection was evaluated, and differences in lipopolysaccharide (LPS)-induced TNF release in infected and uninfected macrophages were determined. Macrophages with in vivo MAC infection released much less TNF alpha in response to LPS (P = .01). The response was partially restored after antimycobacterial therapy. Pentoxifylline, in a concentration that inhibited LPS-induced TNF alpha by 52.4%, increased MAC counts by 2.5- to 50.0-fold. Thus, macrophages from AIDS patients with disseminated MAC infection are deficient in their ability to release TNF alpha, and further inhibition by pentoxifylline may be detrimental.
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PMID:Pentoxifylline aggravates impairment in tumor necrosis factor-alpha secretion and increases mycobacterial load in macrophages from AIDS patients with disseminated Mycobacterium avium-intracellulare complex infection. 803 43

Microsporidia cause opportunistic infections in AIDS patients and commonly infect laboratory animals, as well. Euthymic C57B1/6 mice experimentally infected with intraperitoneal injections of 1 x 10(6) Encephalitozoon cuniculi Levaditi, Nicolau et Schoen, 1923, Encephalitozoon hellem Didier et al., 1991, or Nosema corneum Shadduck et al., 1990 displayed no clinical signs of disease. Athymic mice, however, developed ascites and died 8-16 days after inoculation with N. corneum, 21-25 days after inoculation with E. cuniculi, and 34-37 days after inoculation with E. hellem. All athymic mice displayed hepatomegaly, dilated intestine and accumulation of ascites fluid. Granulomatous lesions are primarily located in the liver, lung, pancreas, spleen, and on serosal surfaces of abdominal organs. The murine microsporidiosis model also was used to examine immune response that inhibit microsporidia growth in vitro. Recombinant murine interferon-gamma (mIFN-gamma, 100 mu/ml) alone or in combination with lipopolysaccharide (LPS; 10 ng/ml) could activate thioglycollate-induced peritoneal murine macrophages to destroy E. cuniculi. The production of the nitrogen intermediate, NO2-, correlated with parasite destruction. Inhibition of NO2- generation by addition of the L-arginine analogue, NG-monomethyl L-arginine (NMMA), inhibited microsporidia killing, as well. Since microsporidiosis is becoming an important opportunistic infection in AIDS patients, a microsporidiosis model is being developed using SIV/DeltaB670-infected rhesus macaque monkeys (Macaca mulatta). SIV-infected immunocompetent monkeys given E. cuniculi or E. hellem per os developed specific antibodies, and microsporidia could be detected sporadically by calcofluor or antibody fluorescence staining of stool and urine sediment smears. As immunodeficiency progressed, monkeys developed diarrhoea, cachexia, and anorexia, and organisms were detected in urine and stool with greater frequency. Immunodeficient SIV-infected monkeys died approximately 27 days after receiving E. hellem by intravenous inoculation, and approximately 110 days after receiving E. hellem per os. Lesions typical for SIV-infection were observed in both groups of monkeys and microsporidia were detected in kidney and liver of the intravenously-injected monkeys. The murine microsporidiosis model provides an efficient means for studying protective immune responses to microsporidiosis, and may prove useful for screening immunological and chemotherapeutic agents. The pathogenesis of Encephalitozoon microsporidiosis in SIV-infected monkeys appears to parallel encephalitozoonosis in AIDS patients, suggesting that simian microsporidiosis may provide a useful model for evaluating diagnostic methods and therapeutic strategies during various stages of progressing immunodeficiency.
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PMID:Experimental microsporidiosis in immunocompetent and immunodeficient mice and monkeys. 805 Jul 48

Soluble tumor necrosis factor (TNF) receptors were recently detected in the circulation of patients with early HIV-induced disease, at significantly higher levels than in control subjects. They were proposed as markers of disease progression and of the degree of immunodeficiency. We report that adsorption of heat-inactivated HIV-1 LAI to isolated human monocytes triggers the release of both TNF-alpha and its natural specific inhibitor, the soluble TNF receptor (sTNF-R)75, but not that of sTNF-R55. Only limited inhibition of sTNF-R release was obtained in the presence of a fully neutralizing anti-TNF-alpha monoclonal antibody, suggesting that stimulation by TNF-alpha was only partially responsible for sTNF-R release. HIV-1 LAI induced a higher sTNF-R/TNF ratio than lipopolysaccharide, a well-known monocyte activator. Monocytes thus represent a cellular source of sTNF-R that can be detected in the circulation of HIV-infected patients from seroconversion onwards. The release of sTNF-R could be of great significance in the control of HIV infection via the cytokine network and especially TNF-alpha.
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PMID:Induction of soluble tumor necrosis factor receptor (sTNF-R75) release by HIV adsorption on cultured human monocytes. 808 26

Previous studies have shown that morphine promotes the replication of human immunodeficiency virus (HIV)-1 in peripheral blood mononuclear cell cocultures. In the present study, we tested the hypothesis that morphine would amplify HIV-1 expression in the chronically infected promonocytic clone U1 when cocultured with lipopolysaccharide-stimulated human fetal brain cells. Marked upregulation of HIV-1 expression was observed in these cocultures (quantified by measurement of HIV-1 p24 antigen levels in supernatants), and treatment of brain cells with morphine resulted in a bell-shaped dose-dependent enhancement of viral expression. The mechanism of morphine's amplifying effect appears to be opioid receptor-mediated and to involve enhanced production of tumor necrosis factor-alpha by microglial cells.
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PMID:Morphine amplifies HIV-1 expression in chronically infected promonocytes cocultured with human brain cells. 812 Jan 38

Tumor necrosis factor alpha (TNF-alpha) is a key mediator of inflammation and may promote human immunodeficiency virus replication in latently infected cells. Since cryptococcosis often is associated with aberrations in the host inflammatory response and occurs preferentially in persons with AIDS, we defined the conditions under which human leukocytes produce TNF-alpha when stimulated by Cryptococcus neoformans. Peripheral blood mononuclear cells (PBMC) produced comparable amounts of TNF-alpha following stimulation with C. neoformans and lipopolysaccharide. Detectable TNF-alpha release in response to C. neoformans occurred only when fungi with small-sized capsules were used and complement-sufficient serum was added. Fractionation of PBMC established that monocytes were the predominant source of TNF-alpha. TNF-alpha gene expression and release occurred significantly later in PBMC stimulated with C. neoformans than in PBMC stimulated with LPS. C. neoformans was also a potent inducer of TNF-alpha from freshly isolated bronchoalveolar macrophages (BAM). Upon in vitro culture, BAM and monocytes bound greater numbers of fungal cells, yet their capacity to produce TNF-alpha following cryptococcal stimulation declined by 74 to 100%. However, this decline was reversed if the BAM and monocytes were cultured with gamma interferon. These data establish that C. neoformans can potently stimulate TNF-alpha release from human leukocytes. However, several variables profoundly affected the amount of TNF-alpha released, including the type of leukocyte and its state of activation, the size of the cryptococcal capsule, and the availability of opsonins.
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PMID:Production of tumor necrosis factor alpha in human leukocytes stimulated by Cryptococcus neoformans. 816 65

Opiates alter a variety of functional activities of the somatic immune system; within the central nervous system, however, their effects on immune responses are unknown. In the present study, we investigated the effect of morphine on the release of tumor necrosis factor (TNF)-alpha from murine neonatal microglia. Microglial cell cultures did not release TNF-alpha when incubated with morphine alone; however, an enhanced (P < .01) release of TNF-alpha was observed when cultures were first primed with morphine for 24 h and then stimulated with lipopolysaccharide. A bell-shaped dose-response curve was observed for the priming effect of morphine; maximal enhancement of TNF-alpha release (310 +/- 15% of control) was detected at a concentration of 10(-10) M morphine. Pretreatment of microglia for 30 min with opioid receptor antagonists (i.e. naloxone and beta-funaltrexamine) completely blocked the priming effect of morphine. In addition, morphine treatment amplified (P < .01) the priming effect of lipopolysaccharide on phorbol myristate acetate-triggered superoxide anion production by microglial cell cultures, and this effect was abrogated (P < .01) by anti-TNF-alpha antibody. Furthermore, culture supernatants derived from microglial cell cultures that had been treated with morphine before stimulation with lipopolysaccharide had an increased capacity to upregulate human immunodeficiency virus-1 expression in the latently infected promonocytic clone U1. This effect was also blocked by anti-TNF-alpha antibody. These findings suggest that morphine primes microglia for enhanced production of TNF-alpha which could alter several functional activities of these cells within the brain.
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PMID:Priming effect of morphine on the production of tumor necrosis factor-alpha by microglia: implications in respiratory burst activity and human immunodeficiency virus-1 expression. 816 25

The RAW264 murine macrophage cell line was used as a model to examine the role of the tat and nef gene products in the transcription regulation of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) in macrophages. Contrary to claims that the activity of the HIV-1 LTR responds poorly in rodent cells to trans activation by the viral tat gene product, cotransfection of RAW264 cells with a tat expression plasmid in transient transfection assays caused a > 20-fold increase in reporter gene expression that was inhibited by mutations in the TAR region. RAW264 cells stably transfected with the tat plasmid displayed similarly elevated HIV-1 LTR-driven reporter gene activity. By contrast to previous reports indicating a negative role for nef in HIV transcription, cotransfection of RAW264 cells with a nef expression plasmid trans activated the HIV-1 LTR driving either a chloramphenicol acetyltransferase or a luciferase reporter gene. The action of nef was specific to the LTR, as expression of nef had no effect on the activity of the simian virus 40, c-fms, urokinase plasminogen activator, or type 5 acid phosphatase promoter. trans-activating activity was also manifested by a frameshift mutant expressing only the first 35 amino acids of the protein. The effects of nef were multiplicative with those of tat gene product and occurred even in the presence of bacterial lipopolysaccharide, which itself activated LTR-directed transcription. Examination of the effects of selected mutations in the LTR revealed that neither the kappa B sites in the direct repeat enhancer nor the TAR region was required as a cis-acting element in nef action. The action of nef was not species restricted; it was able to trans activate in the human monocyte-like cell line Mono Mac 6. The presence of a nef expression cassette in a neomycin phosphotransferase gene expression plasmid greatly reduced the number of G418-resistant colonies generated in stable transfection of RAW264 cells, and many of the colonies that were formed exhibited very slow growth. The frameshift mutant was also active in reducing colony generation. Given the absence of any effect of the frameshift mutation on nef function, its actions on macrophage growth and HIV transcription are discussed in terms of the role of the N-terminal 30 amino acids and of stable secondary structures in the mRNA.
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PMID:Effects of the tat and nef gene products of human immunodeficiency virus type 1 (HIV-1) on transcription controlled by the HIV-1 long terminal repeat and on cell growth in macrophages. 823 Apr 18

The level of human immunodeficiency virus type 1 (HIV-1) in lymphocytes and mononuclear phagocytes (MP) from the blood and pulmonary alveoli from 14 HIV-1-infected subjects during early (asymptomatic) and late (AIDS) stages of disease and the relationship between virus burden in MP and cytokine expression were assessed. Among asymptomatic subjects, HIV-1 was undetectable or low in both blood monocytes and alveolar macrophages (AM). Among subjects with AIDS, there was a significant increase of HIV-1 in AM but not monocytes. The level of HIV-1 in blood lymphocytes was higher than in either monocytes or AM. AM (but not monocytes) expressed increased levels of lipopolysaccharide-stimulated cytokine mRNA (tumor necrosis factor-alpha, interleukin-1 beta, interleukin-6) during both early and late stages of HIV-1 infection regardless of virus load. AM thus may serve as a reservoir for virus in late stages of disease yet contribute to the immunopathogenesis of lung disease in both early and late stages through increased cytokine expression.
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PMID:Relationship between load of virus in alveolar macrophages from human immunodeficiency virus type 1-infected persons, production of cytokines, and clinical status. 827 80

Thalidomide, a selective inhibitor of tumor necrosis factor alpha (TNF-alpha) synthesis, suppresses the activation of latent human immunodeficiency virus type 1 (HIV-1) in a monocytoid (U1) line. The inhibition is dose dependent and occurs after exposure of the cells to recombinant TNF-alpha, phorbol myristate acetate, lipopolysaccharide, and other cytokine combinations. Associated with HIV-1 inhibition is a reduction in agonist-induced TNF-alpha protein and mRNA production. Thalidomide inhibition of virus replication in the phorbol myristate acetate- and recombinant TNF-alpha-stimulated T-cell line ACH-2 is not observed. The presence of thalidomide also inhibits the activation of virus in the peripheral blood mononuclear cells of 16 out of 17 patients with advanced HIV-1 infection and AIDS. These results suggest the use of thalidomide in a clinical setting to inhibit both virus replication and the TNF-alpha-induced systemic toxicity of HIV-1 and opportunistic infections.
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PMID:Thalidomide inhibits the replication of human immunodeficiency virus type 1. 832 69

Exposure of certain cell types to bacterial lipopolysaccharide (LPS) leads to activation of nuclear factor kappa B (NF-kappa B), an inducible transcription factor. One of NF-kappa B's unique properties is its posttranslational activation via release of an inhibitory subunit, called inhibitor of NF-kappa B (I kappa B), from a sequestered cytoplasmic form. This event is also triggered under various other conditions of biomedical importance. Other bacterial toxins, tumor necrosis factor-alpha (TNF), interleukin-1 (IL-1), T cell mitogens, UV light, gamma rays and oxidative stress were reported to induce NF-kappa B. The activated form of NF-kappa B, which is rapidly taken up into nuclei, initiates transcription from immediate early genes in a wide variety of cell types. Most of the target genes for NF-kappa B are of relevance for the immune response and can be grouped into those encoding cytokines, cell surface receptors, acute phase proteins and viral genomes, such as that of human immunodeficiency virus type 1 (HIV-1). We will discuss recent experimental evidences suggesting that LPS might share a pathway of NF-kappa B activation with other inducers of the factor. This common pathway may involve reactive oxygen intermediates (ROI) as messenger molecules.
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PMID:Nuclear factor kappa B, a mediator of lipopolysaccharide effects. 833 Aug 98


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