Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously observed that HIV-1 replication is suppressed in uninflamed lung and increased during tuberculosis. In vitro THP-1 cell-derived macrophages inhibited HIV-1 replication after infection with Mycobacterium tuberculosis. Suppression of HIV-1 replication was associated with inhibition of the HIV-1 long terminal repeat (LTR) and induction of ISGF-3, a type I interferon (IFN)-specific transcription factor. Repression of the HIV-1 LTR required intact CCAAT/enhancer binding protein (C/EBP) sites. THP-1 cell-derived macrophages infected with M. tuberculosis, lipopolysaccharide, or IFN-beta induced the 16-kD inhibitory C/EBPbeta isoform and coincidentally repressed HIV-1 LTR transcription. C/EBPbeta was the predominant C/EBP family member produced in THP-1 macrophages during HIV-1 LTR repression. In vivo, alveolar macrophages from uninflamed lung strongly expressed inhibitory 16-kD C/EBPbeta, but pulmonary tuberculosis abolished inhibitory C/EBPbeta expression and induced a novel C/EBP DNA binding protein. Therefore, in vitro, proinflammatory stimulation produces an IFN response inhibiting viral replication by induction of a C/EBPbeta transcriptional repressor. THP-1 cell-derived macrophages stimulated with type I IFN are similar to alveolar macrophages in the uninflamed lung in vivo. In contrast, the cellular immune response in active pulmonary tuberculosis disrupts this innate immunity, switching C/EBP expression and allowing high level viral replication.
 ...
PMID:Type I interferon induces inhibitory 16-kD CCAAT/ enhancer binding protein (C/EBP)beta, repressing the HIV-1 long terminal repeat in macrophages: pulmonary tuberculosis alters C/EBP expression, enhancing HIV-1 replication. 976 5

Microbial coinfections variably influence HIV-1 infection through immune activation or direct interaction of microorganisms with HIV-1 or its target cells. In this study, we investigated whether exposure of macrophages to bacterial products impacts the susceptibility of these cells to HIV-1 of different cellular tropisms. We demonstrate that () macrophages exposed to bacterial cell wall components such as lipopolysaccharide (LPS) (Gram-negative rods), lipoteichoic acid (Gram-positive cocci), and lipoarabinomannan (Mycobacteria) become highly susceptible to T cell (T)-tropic HIV-1 (which otherwise poorly replicate in macrophages) and variably susceptible to macrophage (M)-tropic HIV-1; () LPS-stimulated macrophages secrete a number of soluble factors (i.e., chemokines, interferon, and proinflammatory cytokines) that variably affect HIV infection of macrophages, depending on the virus phenotype in question; and () LPS-stimulated macrophages express CCR5 (a major coreceptor for M-tropic HIV-1) at lower levels and CXCR4 (a major coreceptor for T-tropic HIV-1) at higher levels compared with unstimulated macrophages. We hypothesize that a more favorable environment for T-tropic HIV-1 and a less favorable or even unfavorable environment for M-tropic HIV-1 secondary to exposure of macrophages to those bacterial products may accerelate a transition from M- to T-tropic viral phenotype, which is indicative of disease progression.
 ...
PMID:Exposure to bacterial products renders macrophages highly susceptible to T-tropic HIV-1. 978 67

Improvements in HIV-1 vaccines are urgently needed since many of the available vaccines are weak immunogens. We examined the ability of CRL1005, a novel nonionic block copolymer adjuvant, to improve the immunogenicity of multiple HIV-1 envelope vaccines: six gp120s and single and multiple V3 peptides (MAPs). Formulation of vaccine with adjuvant, as compared with alum or saline, enhanced antibody titer in mice up to 200-fold, with antibody half-lives of >200 days. For most vaccinations, an oil-in-water formulation induced the highest antibody titers; for some antigens, however, particularly single peptides, water-in-oil (w/o) was better. Antigen cross-reactivity was optimized by formulation in w/o, while addition of detoxified lipopolysaccharide enhanced levels of IgG2a and IgG2b. After more than 1 year of observation, no vaccine-related toxicity was observed and emulsified antigen in encapsulated depots was found at immunization sites of w/o-immunized animals. No other adjuvant has been reported to induce such long-lasting antibodies, and the ability of CRL1005 to greatly amplify and qualitatively modify antibody responses suggests that it may be useful in developing improved HIV vaccines for humans.
 ...
PMID:Enhancement of HIV type 1 vaccine immunogenicity by block copolymer adjuvants. I. Induction of high-titer, long-lasting, cross-reactive antibodies of broad isotype. 982 24

Although the precise mechanisms whereby HIV-1 infection induces neurodegeneration have yet to be determined, a great deal of evidence has incriminated glial cells and the production of proinflammatory mediators in this pathologic process. For this reason, ideal therapeutic agents for the treatment of AIDS dementia would attenuate HIV-1 neuropathogenesis through both direct inhibition of viral expression and suppression of brain cell-produced immune mediators. Benzodiazepines (BDZs), such as Valium, are extensively prescribed drugs for anxiety disorders, which readily cross the blood-brain barrier and have demonstrated immunomodulatory properties. BDZs bind to primary human microglial cells, the principal site of HIV-1 replication in the brain, and inhibit lipopolysaccharide (LPS) induced tumour necrosis factor (TNF-alpha) production by these cells in a concentration-dependent manner. Treatment of HIV-1-infected primary human microglial, as well as mixed glial/neuronal, cell cultures with BDZs inhibits the expression of HIV-1 p24 antigen. BDZ-induced inhibition of HIV-1 expression in chronically infected promonocytic (U1) cells has been found to be associated with decreased activation of the nuclear transcription factor kappa B (NF-kappa B). Because HIV-1 expression is critically dependent on the cellular transcription machinery, inhibition of the activation of transcription factors, which participate in both HIV-1 expression and the production of neurotoxic immune mediators, by BDZ analogs may provide new therapeutic options for AIDS dementia.
 ...
PMID:Benzodiazepines, glia, and HIV-1 neuropathogenesis. 982 47

Phenylarsine oxide (PAO), which is described as an inhibitor of tyrosine phosphatase activity, inhibits H2O2 release from human peripheral blood mononuclear cells (PBMCs) as measured by electrochemistry. Since human immunodeficiency virus type 1 (HIV-1) replication is known to be favored under oxidative stress conditions, ex vivo experiments using uninfected PBMCs, primary monocytes or a latently infected promonocytic U1 cell line show that HIV-1 replication and reactivation, monitored by p24 antigen measurement, are inhibited by PAO in a time- and concentration-dependent manner. These observations can be linked with the inhibition of NF-kappa B activation when uninfected monocytes are induced by either tumor necrosis factor alpha (TNF-alpha) phorbol 12-myristate 13-acetate (PMA) or lipopolysaccharide (LPS).
 ...
PMID:Phenylarsine oxide inhibits ex vivo HIV-1 expression. 986 1

A major question relevant to the initiation and progression of inflammation and autoimmune processes within the central nervous system (CNS) is whether resident microglia or only infiltrating macrophage can productively interact with T-cells that enter the CNS either actively through extravasation or passively through defects in the blood brain barrier (BBB). We isolated microglia and macrophage from the brains of healthy adult mice and transgenic mice that displayed many features of multiple sclerosis and HIV leukoencephalopathy due to the astrocytic expression of interleukin (IL)-3 and compared their antigen-presenting cell (APC) functions. We found that unactivated microglia isolated from healthy nontransgenic mice and activated microglia isolated from transgenic siblings are relatively weak stimulators of naive T-cell proliferation compared to macrophage populations. The APC function of activated, but not unactivated, microglia could be increased by treatment acutely with lipopolysaccharide (LPS)/interferon gamma (IFN-gamma). However, this treatment also induced the apparent production of prostaglandins, which reduced T-cell proliferation when indomethacin was absent from the assay cultures. Strikingly, even in the absence of stimulated T-cell proliferation, both unactivated and activated microglia stimulated the differentiation of naive T-cells into Th1 effector cells, although neither microglial population was a more effective inducer than macrophages or splenic APCs. Thus, while microglia are clearly capable of productively interacting with naive T-cells, macrophages have a more robust APC function.
 ...
PMID:Microglia stimulate naive T-cell differentiation without stimulating T-cell proliferation. 989 Apr 41

Brain prostanoid levels are normally low but can increase after ischemia and during inflammatory and infectious diseases. High prostanoid levels can affect brain function in several ways. In particular, prostaglandin E2 (PGE2) might exert both immunodepressive and proinflammatory actions. The present short review focuses on the regulation of prostanoid synthesis in microglial cultures and on the possible role of PGE2 in the down-regulation of microglial activation induced by lipopolysaccharide (LPS). Our studies were carried out using purified mouse or rat microglial cultures. LPS induced a dose-dependent expression of the inducible isoform of cyclooxygenase (COX-2), both in neonatal and adult microglial cultures. In the latter, the inducibility of COX-2 increased with time in culture, paralleling the acquisition of a more 'activated' microglial phenotype, and appeared to account for the time-dependent increase in the PGE2/TXB2 production ratio. The LPS-induced COX-2 expression and prostanoid production were down-regulated by potentially neurotoxic agents, such as nitric oxide (NO), the proinflammatory cytokine IFN-gamma (which acted both directly and indirectly, through its NO-inducing activity) and the HIV regulatory protein tat. On the other hand, COX-2 expression was up-regulated by the macrophage-deactivating cytokine TGF-beta 1, by exogenous PGE2 itself, which acted through EP2 receptors linked to cyclic AMP generation, and by non steroidal anti-inflammatory drugs. Interestingly, PGE2 utilized the same EP2 receptor-mediated signal transduction mechanism to down-regulate the expression of the inducible NO synthase and the production of NO. Largely, but not exclusively, through its effect on cyclic AMP, PGE2 can also: i) depress the expression of major histocompatibility complex class II antigens and of the costimulatory molecule B7-2; ii) down-regulate TNF and up-regulate IL-10 microglial production; iii) inhibit microglial IL-12 secretion. These observations, together with literature data on in vivo models of central nervous system (CNS) diseases, suggest a neuroprotective role of PGE2 in pathological conditions.
 ...
PMID:Regulation of prostanoid synthesis in microglial cells and effects of prostaglandin E2 on microglial functions. 989 49

Previous work suggests that gp120 mediates the passage of HIV-1 and infected immune cells across the blood-brain barrier (BBB) by induction of adsorptive endocytosis (AE) in brain endothelial cells. Other work has suggested that cytokines may increase the permeability of the BBB to free virus or infected immune cells. Here, we investigated the ability of lipopolysaccharide (LPS), a bacterial wall toxin that stimulates the release of cytokines, to increase gp120 passage across the BBB by enhancement of AE and/or induction of BBB disruption. We found that LPS enhanced the passage of gp120 radioactively labeled with 125I (I-gp120) in a reversible, time-dependent, prostaglandin-independent manner that was not completely explained by disruption of the BBB. LPS also enhanced wheatgerm agglutinin mediated uptake of I-gp120 almost exclusively through the potentiation of AE. These results show that LPS or cytokines released by LPS can have a major effect on the permeability of the BBB to HIV-1gp120 both by stimulating AE and by inducing a disruption of the BBB. This suggests that bacterial infection or other inflammatory states could facilitate invasion of the CNS by HIV-1.
 ...
PMID:Adsorptive endocytosis of HIV-1gp120 by blood-brain barrier is enhanced by lipopolysaccharide. 1019 87

HIV-1 infection of the central nervous system can cause severe neurologic disease although only microglial cells and brain macrophages are susceptible to productive viral infection. Substances secreted by infected cells are thought to cause disease indirectly. Tumor necrosis factor alpha (TNF-alpha) is one candidate neurotoxin and is upregulated during HIV-1 infection of the brain, likely via activation of the transcription factor NF-kappaB. We used the proteasome inhibitors, MG132 and ALLN (N-acetyl-Leu-Leu-Norleucinal), to inhibit NF-kappaB activation in primary human fetal microglia (PHFM) and primary monocyte derived-macrophages, and showed that they could block TNF-alpha release stimulated by lipopolysaccharide (LPS) or TNF-alpha. In addition, we performed electrophoretic mobility shift analysis and determined that in microglia, the p50/p65 heterodimer of NF-kappaB is activated by LPS stimulation, and is inhibited by MG132. Thus, blockade of NF-kappaB activation in microglia in vitro can decrease production of TNF-alpha and may prove to be a novel strategy for treating HIV-1 dementia.
 ...
PMID:Proteasome blockers inhibit TNF-alpha release by lipopolysaccharide stimulated macrophages and microglia: implications for HIV-1 dementia. 1022 15

It is known that sulfated polysaccharides can mimic the action of common T-cell mitogens. To investigate the molecular basis of the mitogenic effect of high molecular weight dextran sulfate (HMDS), monocyte-derived macrophages were transfected with recombinant plasmid containing chloramphenicol acetyl transferase (CAT) reporter gene under the control of the HIV-1 long terminal repeat (LTR) promoter, which is regulated by transcription factor NF-kappaB. We observed that HMDS, similar to bacterial lipopolysaccharide (LPS), increases the expression of CAT reporter gene suggesting increased activity of NF-kappaB. The activation of NF-kappaB correlated with the increased expression of B7.1 molecules. It was postulated that this NF-kappaB-regulated promoter might play a role in the activation of the accessory cells as well as the rate of replication of HIV-1 in monocyte-derived macrophages.
 ...
PMID:High molecular weight dextran sulfate increases the activity of NF-kappaB-regulated promoter in monocyte-derived macrophages. 1022 75


<< Previous 1 2 3 4 5 6 7 8 9 10