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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proinflammatory cytokines interleukin (IL)-1 and tumor necrosis factor (TNF) promote HIV type 1 viral replication in vitro. In the present studies, HIV production was increased in the macrophagic U1 cell line expressing the HIV genome after exposure to IL-1beta, osmotic stress, or surface adhesion, suggesting a confluence of signaling pathways for proinflammatory cytokines and cell stressors. The p38 mitogen-activated protein kinase (MAPK) mediates both cytokine and stress responses; thus the role of this kinase in HIV production was investigated. HIV production as measured by p24 antigen correlated with changes in the expression of a specific (non-alpha) isoform of p38 MAPK. In the presence of a specific p38 MAPK inhibitor (p38 inh), IL-1beta-induced HIV production was suppressed by more than 90% and IL-1beta-induced IL-8 production was suppressed completely, both with IC50 of 0.01 microM. p38 inhibition blocked cell-associated p24 antigen and secreted virus to a similar extent. The p38 inh also decreased constitutive HIV production in freshly infected peripheral blood mononuclear cells by up to 50% (P < 0.05). Interruption of p38 MAPK activity represents a viable target for inhibition of HIV.
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PMID:Role of p38 mitogen-activated protein kinase in HIV type 1 production in vitro. 963 65

Accumulating data from a number of laboratories have recently indicated that the response of transcription factor NF-kappaB to alterations in the redox homeostasis of cells may play an important role in modulating immune function. The activation of NF-kappaB has been recognized to regulate a number of genes necessary for normal T cell responses including IL-2, IL-6, IL-8, and several T cell surface receptors. Diminished NF-kappaB activity has been shown to occur in T cells with aging, suggesting that impaired activation of NF-kappaB might occur during cellular senescence. In addition, aberrancies in NF-kappaB activity have been implicated in the immunopathogenesis of diseases involving immune or inflammatory processes such as atherosclerosis and HIV-1 infection. The role of H2O2 and other reactive oxygen species (ROS) as an integratory secondary messenger for divergent T cell signals has been complicated by the fact that various T cell lines and peripheral blood T cells differ markedly in the levels of NF-kappaB activation induced by oxidant stress. Additionally, proposed pathways of NF-kappaB activation have been based on indirect evidence provided by experiments which used antioxidants to inhibit active NF-kappaB formation. Further, complete activation of T cells requires at least two signals, one that stimulates an increase in intracellular calcium and one that stimulates enzymatic processes including kinases. Similarly, substantial evidence indicates that full activation of NF-kappaB requires dual signals. The ability of H2O2 or other ROS to induce T cell signals and functional responses by these two mechanisms is reviewed and the specific response of NF-kappaB to redox changes in T cells is examined. Data are also presented to suggest that the redox regulation in NF-kappaB activation may be relevant to immune-related diseases and to aging.
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PMID:Redox signals and NF-kappaB activation in T cells. 968 Jan 81

Posttranslational processing of chemokines increases (IL-8) or decreases (monocyte chemotactic protein-1) their chemotactic potency. Macrophage-derived chemokine (MDC) attracts monocytes, dendritic cells, activated lymphocytes, and NK cells and has reportedly anti-HIV-1 activity. Here we report that truncation of MDC by deletion of two NH2-terminal residues resulted in impaired binding to CC chemokine receptor (CCR)4, the only identified MDC receptor so far. Truncated MDC(3-69) failed to desensitize calcium mobilization by MDC(1-69) or thymus- and activation-regulated chemokine (TARC), another CCR4 ligand. MDC(3-69) lacked HUT-78 T cell chemotactic activity but retained its capacity to attract monocytes and to desensitize chemotaxis. Compared with MDC(1-69), MDC(3-69) had weak but enhanced antiviral activity against M- and T-tropic HIV-1 strains. Furthermore, both MDC forms failed to signal through the orphan receptors Bonzo/STRL33 and BOB/GPR15 and to desensitize RANTES and stromal cell-derived factor (SDF)-1 responses in CCR5-transfected and CXC chemokine receptor (CXCR)4-transfected cells, respectively. These findings suggest that MDC recognizes another, yet unidentified, receptor. We conclude that minimal NH2-terminal truncation of MDC differentially affects its various immunologic functions.
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PMID:Enhanced anti-HIV-1 activity and altered chemotactic potency of NH2-terminally processed macrophage-derived chemokine (MDC) imply an additional MDC receptor. 974 22

The cytokine interleukin (IL) 18 (formerly interferon gamma-inducing factor) induces the T helper type 1 response. In the present studies, IL-18 increased HIV type 1 (HIV-1) production from 5- to 30-fold in the chronically infected U1 monocytic cell line. Inhibition of tumor necrosis factor (TNF) activity by the addition of TNF-binding protein reduced IL-18-stimulated HIV-1 production by 48%. In the same cultures, IL-18-induced IL-8 was inhibited by 96%. Also, a neutralizing anti-IL-6 mAb reduced IL-18-induced HIV-1 by 63%. Stimulation of U1 cells with IL-18 resulted in increased production of IL-6, and exogenous IL-6 added to U1 cells increased HIV-1 production 4-fold over control. A specific inhibitor of the p38 mitogen-activated protein kinase reduced IL-18-induced HIV-1 by 73%, and a 50% inhibition was observed at 0.05 microM. In the same cultures, IL-8 was inhibited by 87%. By gel-shift and supershift analyses, increased binding activity of the transcription factor NF-kappaB was measured in nuclear extracts from U1 cells 1 h after exposure to IL-18. These results demonstrate induction of HIV-1 by IL-18 in a monocyte target associated with an intermediate role for TNF and IL-6, activation of p38 mitogen-activated protein kinase, and nuclear translocation of NF-kappaB.
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PMID:Interleukin 18 stimulates HIV type 1 in monocytic cells. 977 May 23

Very little is known about the pathogenesis of pulmonary non-tuberculous mycobacteriosis in immunocompetent individuals. Local inflammatory response was assessed by examining bronchoalveolar lavage fluid from 13 HIV-negative patients (12 F) without known cell-mediated immunosuppression, aged 48-72 y (median age 60 y), with non-tuberculous lung mycobacteriosis. Macrophages, lymphocytes, polymorphonuclear neutrophils and eosinophils in bronchoalveolar lavage fluid were analysed morphologically, and the subsets of T-lymphocytes (CD3+, CD4+, CD8+), HLA-DR+, B-lymphocytes (CD19+) and CD16+/CD56+ cells (natural killer, NK cells) were analysed by flow cytometry. Interleukin-1 beta (IL-1beta), IL-2, IL-4, IL-6, IL-8, IL-10 and interferon-gamma (IFN-gamma) levels were assessed by ELISA. The total number of cells/ml was significantly higher in BAL fluid from the patients (median value=880 x 10(3)/ml) compared to six healthy controls (200 x 10(3)/ml). The polymorphonuclear neutrophil population was significantly increased in the patients both proportionally and in the count/ml. The proportion of macrophages was significantly reduced in the patients but not the count/ml. The count of lymphocytes/ml was significantly higher in the patients but the proportion of lymphocytes was unchanged. No significant difference was seen in the relative proportion of NK cells, B- or T-lymphocytes and HLA-DR+ compared to the healthy controls. The IL-1beta and IL-8 levels were significantly increased in the patients. No differences were seen between the patients and controls in the leukocyte or lymphocyte subsets in peripheral blood. The local inflammatory response in BAL fluid from the studied patients was characterized by granulocytosis, and increase in the IL-1beta and IL-8 levels. There was no specific T-cell response.
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PMID:Lack of T-lymphocytosis and poor interferon gamma production in BAL fluid from HIV-negative immunocompetent patients with pulmonary non-tuberculous mycobacteriosis. 981 11

Marijuana, a widely abused drug in the US, and its derivatives (cannabinoids) have been used in AIDS and cancer patients for treatment of intractable nausea and cachexia. Yet, objective investigations of the effect of cannabinoids on the human immune system are few. We investigated the effect of delta9 tetrahydrocannabinol (THC) and cannabidiol (CBD) on cytokine production in vitro by human leukemic T, B, eosinophilic and CD8+ NK cell lines as models. THC decreased constitutive production of IL-8, MIP-1alpha, MIP-1beta, and RANTES and phorbol ester stimulated production of TNF-alpha, GM-CSF and IFN-gamma by NK cells. It inhibited MIP-1beta in HTLV-1 positive B-cells but tripled IL-8, MIP-1alpha and MIP-1beta in B-cells and MIP-1beta in eosinophilic cells but doubled IL-8. Both cannabinoids strongly inhibited IL-10 production by HUT-78 T-cells. Results indicate that THC and nonpsychotropic CBD have complex lineage and derivative specific effects on cytokines consistent with previous animal studies. These effects while of potential benefits in some inflammatory/autoimmune diseases may worsen HIV infection, tumorigenesis and allergic inflammation in the lung.
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PMID:Delta9 tetrahydrocannabinol and cannabidiol alter cytokine production by human immune cells. 985 61

We show that infection of primary monocyte-derived macrophages (MDMs) and blood lymphocytes (PBLs) by human immunodeficiency virus type 1 (HIV-1) R5 strains, but not that of PBLs by X4 strain HIV-1LAI, is inhibited by beta-chemokines RANTES and MIP-1alpha. A biotinylated disulfide-bridged peptide mimicking the complete loop of clade B consensus V3 domain of gp120 (V3Cs), but not a biotinylated V3LAI peptide or a control beta-endorphin peptide of approximately the same molecular weight (MW), was found to bind specifically to MDM membrane proteins, in particular two proteins of 42 and 62 kDa migrating as sharp bands after electroblotting onto Immobilon, and this was specifically inhibited by anti-V3 antibodies. When biotinylated V3Cs was incubated with intact MDMs, which were then washed and lysed, and the resulting material was incubated with streptavidin-agarose beads and electroblotted onto Immobilon, fresh V3Cs also bound to proteins of the same molecular weight recovered in the V3Cs-interacting material. This binding was inhibited by anti-V3 antibodies, and no binding occurred with the control peptides. V3Cs also bound to soluble recombinant CD4, and CD4 monoclonal antibody Q4120 specifically recognized the V3Cs-interacting 62-kDa protein, which should thus correspond to CD4. Recombinant radiolabeled RANTES, MIP-1alpha, and MIP-1beta, but not IL-8, also bound to a 42-kDa protein on the membrane of MDMs as well as to the V3Cs-interacting 42-kDa protein, and excess unlabeled V3Cs inhibited such binding. This protein was also recognized by antibodies to CCR5, the RANTES/MIP-1alpha/MIP-1beta receptor. These data show that V3Cs binds to MDM membrane proteins that comprise CD4 and CCR5, and that multimolecular complexes involving at least gp120 V3, CD4, and CCR5 are formed on the surface of MDMs as part of V3-mediated postbinding events occurring during HIV-1 infection.
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PMID:Interaction of human immunodeficiency virus type 1 envelope glycoprotein V3 loop with CCR5 and CD4 at the membrane of human primary macrophages. 987 Mar 13

The Duffy Antigen Receptor for Chemokines (DARC) belongs to a family of erythrocyte chemokine receptors that bind C-X-C and C-C chemokines such as interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1) and regulated-on-activation, normal T cell-expressed and -secreted (RANTES), but not macrophage inflammatory protein 1 alpha (MIP-1 alpha) or MIP-1 beta. DARC has also been identified to a receptor for malaria parasites Plasmodium vivax and Plasmodium knowlesi. In the present study, we show that HIV-1 binds to RBCs from Caucasian individuals via DARC making RBCs able to transmit HIV to peripheral blood mononuclear cells (PBMCs). Furthermore, binding of HIV-1 particles to RBCs is inhibited by treating these cells with recombinant RANTES, but not with recombinant MIP-1 alpha prior to their incubation with HIV-1. This finding suggests that RBCs may function as a reservoir for HIV-1 or as a receptor for the entry of HIV-1 into CD4-cell subsets as well as neurons or endothelial cells.
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PMID:Binding of HIV-1 to RBCs involves the Duffy antigen receptors for chemokines (DARC). 992 12

Interleukin-8 (IL-8) production in vivo was monitored in four study groups: normal blood donors, patients with pulmonary tuberculosis (TB), patients with human immunodeficiency virus type 1 (HIV-1) infection, and dually infected (HIV/TB) patients. We show that whereas there was evidence of detectable levels of cell-associated IL-8 (mRNA and protein) in peripheral cells of healthy individuals, this was largely lost in the disease states studied. Coupled with this finding was significantly increased circulating levels of IL-8 in HIV-1-infected individuals with or without concomitant pulmonary TB (P < 0.001). On the other hand, the capacity of peripheral mononuclear cells to produce IL-8 spontaneously ex vivo was enhanced in HIV-1 and TB patients (P < 0.05) and many of the HIV/TB group, but their corresponding capacities to respond to various stimuli, in particular phytohemagglutinin, were significantly diminished compared to those of normal donors (P < 0.05). Circulating levels of IL-8 in a group of HIV/TB patients were significantly positively correlated with the percentage of polymorphonuclear leukocytes (PMN) in the peripheral circulation (r = 0.65; P = 0.01), the proportions of IL-8 receptor A (IL-8RA)-expressing (r = 0.86; P < 0.01) and IL-8RB-expressing (r = 0.77; P < 0.01) PMN, and the capacity of PMN to migrate in response to IL-8 as chemoattractant (r = 0.68; P < 0. 01). IL-8RB fluorescence intensity, however, was negatively correlated with plasma IL-8 levels (r = -0.73; P < 0.01). Our results suggest that altered regulation of IL-8 in HIV-1 may have important implications for antimicrobial defenses and for normal immune processes.
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PMID:Dysregulated production of interleukin-8 in individuals infected with human immunodeficiency virus type 1 and Mycobacterium tuberculosis. 1002 68

CC chemokine receptor 5 (CCR5) is a cell entry cofactor for macrophage-tropic isolates of human immunodeficiency virus 1 (HIV-1). An inactive CCR5 allele with a 32-nucleotide deletion (CCR5Delta32) has been described that confers resistance to HIV-1 infection in homozygotes and slows the rate of progression to AIDS in heterozygotes. We found the allele CCR5Delta32 to be not rare in 399 Swiss blood donors with a frequency of 0.080. To assess the influence of defective CCR5 on production of its ligands we determined the capacity to produce the chemokines macrophage inflammatory protein (MIP)-1alpha, MIP-1beta and RANTES in comparison with the production of the CXC chemokine IL-8 which does not bind to CCR5. Production of chemokines was determined during endotoxin stimulation of whole-blood samples ex vivo. Both, basal and LPS-induced chemokine production in 32 blood donors heterozygous for CCR5Delta32 were not significantly different when compared with 55 blood donors who were homozygous for the wild type CCR5 allele.
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PMID:Heterozygous defect in HIV-1 coreceptor CCR5 and chemokine production. 1008 Aug 73


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