UMLS:C0019693 - FACTA Search

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

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

Tumor necrosis factor-alpha (TNF-alpha) is a highly pleiotropic cytokine produced mainly by activated macrophages. This cytokine has been found to mediate the growth of certain tumors, the replication of HIV-1, septic shock, cachexia, graft-versus-host disease, and autoimmune diseases. The binding of TNF-alpha to the p55 tumor necrosis factor receptor type I (TNFRI) is considered one of the initial steps responsible for the multiple physiologic effects mediated by TNF-alpha. The role of TNF-alpha as an inflammatory mediator through TNFRI makes both of these genes attractive targets for intervention in both acute and chronic inflammatory diseases. We have designed antisense oligodeoxynucleotides (ODNs) containing chemically modified purine and pyrimidine bases that specifically inhibit TNFRI expression and functions. These ODNs were designed to hybridize to the 3'-polyadenylation signal region of the TNFRI gene. In cell-based assays, gene-specific antisense inhibition occurred in a dose-dependent fashion at submicromolar concentrations in the presence of cellular uptake enhancing agents. Within ODN sets with a common pattern of stabilizing backbone substitution, the inhibition of the gene expression is found to be correlated with the affinity of the ODNs for their cognate mRNA target sites, providing direct evidence for an antisense mechanism of action. In addition, events triggered by the binding of TNF-alpha to TNFRI, such as the production of IL-6 and IL-8, were significantly reduced by treatment of cells with the anti-TNFRI ODN. Therefore, antisense ODNs can be used to control biologic processes mediated by TNF-alpha and may be useful as therapeutic agents to treat conditions resulting from overproduction of TNF-alpha.
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PMID:Sequence-specific inhibition of the tumor necrosis factor-alpha receptor I gene by oligodeoxynucleotides containing N7 modified 2'-deoxyguanosine. 936 4

Treatment of primary monocytes with soluble HIV-Tat protein is associated with increased monocyte metalloproteinase-9 (MMP-9) expression and enhanced beta 2 integrin expression that increases monocyte/endothelial adhesion. These alterations require greater than 12 h of HIV-Tat treatment, suggesting the involvement of intermediate factors. Thus, we have examined the role of cytokines in the HIV-Tat-induced alteration of monocyte function. Treatment of monocytes with HIV-Tat rapidly up-regulated the production of IL-1 beta, IL-6, IL-8, and TNF-alpha, but not IL-3, granulocyte-macrophage CSF, basic fibroblast growth factor, or macrophage-inflammatory protein-1 alpha, and was associated with up-regulation of the corresponding cytokine mRNA. Inclusion of neutralizing anti-cytokine Abs to IL-1 beta or TNF-alpha during the HIV-Tat pretreatment period significantly inhibited the HIV-Tat-induced increase in MMP-9 production, monocyte/endothelial adhesion, and monocyte-dependent endothelial damage. In contrast, neutralizing Abs against IL-6 and IL-8 had no effect. The effects of HIV-Tat treatment, namely MMP-9 production, enhanced monocyte/endothelial cell adhesion, and monocyte-dependent endothelial damage, were mimicked by treating the monocytes with IL-1 beta or TNF-alpha, but not with IL-6 or IL-8. Therefore, the mechanism by which HIV-Tat activates monocyte function is dependent on HIV-Tat-induced production of cytokines (IL-1 beta and TNF-alpha).
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PMID:Activation of monocytes by HIV-Tat treatment is mediated by cytokine expression. 937 98

Blood monocytes from patients with active tuberculosis are activated in vivo, as evidenced by an increase in the stimulated release of proinflammatory cytokines, such as TNF-alpha, and the spontaneous expression of IL-2R. Further, monocytes from patients demonstrate an augmented susceptibility to a productive infection with HIV-1 in vitro. Mycobacterium tuberculosis and its components are strong signals to activate monocytes to production of cytokines. In this study we examined the basis of activation of monocytes during active tuberculosis and by M. tuberculosis. We found a constitutive degradation of I kappa B-alpha, the major cytoplasmic inhibitor of nuclear factor kappa B (NF-kappa B), in freshly isolated PBMC and monocytes from patients with tuberculosis. In contrast, I kappa B-alpha levels in PBMC and monocytes from healthy subjects or from patients with nontuberculous pulmonary conditions were intact. Further, by electrophoretic mobility shift assay, NF-kappa B was activated in monocytes from tuberculous patients. The expression of I kappa B-alpha gene, which is responsive to activation by NF-kappa B, was up-regulated in PBMC and monocytes from patients, but not in mononuclear cells from healthy subjects or those with nontuberculous lung diseases. By contrast, the expression of other adherence-associated early genes, such as IL-8 and IL-1 beta, was not up-regulated in PBMC of tuberculous patients. Further, M. tuberculosis and its tuberculin, purified protein derivative, induced the degradation of I kappa B-alpha and the expression of I kappa B-alpha mRNA, and purified protein derivative induced the activation of NF-kappa B in monocytes.
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PMID:Regulation of nuclear factor-kappa B and its inhibitor I kappa B-alpha/MAD-3 in monocytes by Mycobacterium tuberculosis and during human tuberculosis. 937 2

A structural model of interleukin-8 receptor type beta (IL-8R-beta) was constructed based on the structure of bacteriorhodopsin. High temperature molecular dynamics simulations were performed to search the possible conformations of loop regions in IL-8R-beta which recognize the ligand. The crystal structure of interleukin 8 (IL-8) was used as a geometric constraint of the extracellular loop regions of IL-8R-beta in the conformational search. 500 complex structures were extracted from the dynamics trajectory and five plausible models were selected based on the binding energy and known experimental data. To study further the interaction between IL-8R-beta and its ligands, the complex of IL-8R-beta and platelet factor 4 (PF4) C-terminal peptide was also modeled by molecular dynamics simulations. From these models, the N-terminus, extracellular domain 3 and extracellular domain 4 of IL-8R-beta were found to be important for ligand binding. Key residues of these regions involved in ligand binding were characterized. These models provide insight into the structural basis of biological activity of IL-8 and PF4 and may guide the design of potential therapeutic agents targeting IL-8 receptors. Furthermore, the approach developed from this study may have implications for the understanding of other chemokine receptor-ligand interactions that have been recently suggested to be involved in HIV infection.
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PMID:Molecular modeling of interleukin-8 receptor beta and analysis of the receptor-ligand interaction. 946 67

The beta-chemokines RANTES, MIP-1alpha, and MIP-1beta have been shown to inhibit the infection of T cells by macrophage-tropic HIV-1 strains by blocking env-driven HIV-1 fusion through competition for the chemokine receptors or receptor downregulation. This study was aimed at testing whether beta-chemokines also inhibit the productive infection of monocyte-derived macrophages (MDMs) by a monocytotropic HIV-1 strain, by using virus yield assays. The action of the beta-chemokines MIP-1alpha, MIP-1beta, and RANTES was captured with that of the alpha-chemokine interleukin 8 (IL-8) and of interferon alpha (IFN-alpha), which is a well-known broad-range inhibitor of viral replication. While IL-8 did not inhibit HIV-1 BaL replication in MDMs, the beta-chemokines were dose-dependently inhibitory. RANTES was the most effective, reaching at 300 ng/ml a protection similar to that obtained with IFN-alpha at 1000 IU/ml, and was even more inhibitory when added to MDMs after virus attachment. In contrast to IFN-alpha, the antiviral activity of beta-chemokines was restricted to HIV, because another virus was not inhibited. As compared with untreated MDMs, full-length proviral DNA at day 1 postinfection was inhibited in MDMs treated with RANTES either before or after the absorption phase, and even more so in IFN-treated MDMs, whereas in IL-8-treated MDMs no inhibition was observed. Our results indicate that in MDMs both RANTES and IFN affect early steps of HIV-1 BaL replication, preceding the completion of viral DNA synthesis.
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PMID:Inhibition of HIV type 1 BaL replication by MIP-1alpha, MIP-1beta, and RANTES in macrophages. 949 13

Elevated levels of circulating IL-8, a potent chemotactic factor for granulocytes and T lymphocytes, are found in HIV-infected individuals. The HIV-1 transactivator protein Tat increased IL-8 secretion in T cell lines following CD3- and CD28-mediated costimulation. Full-length Tat (Tat101) enhanced IL-8 transcription through up-regulated transcription factor binding to the CD28-responsive element (CD28RE) in the IL-8 promoter. Expression of the Tat splice variant Tat72 (72 amino acids) also enhanced IL-8 production following T cell stimulation via a different, most likely post-transcriptional, mechanism. The CD28RE in the IL-8 promoter was characterized as a low-affinity NF-kappaB binding site recognized by the transcription factors p50 (NF-kappaB1), p65 (RelA) and c-rel. Transcription factor binding to "classical" NF-kappaB sites in the HIV-1, the human IL-2, and lymphotoxin promoters, recognized by p50 and p65 following CD3+28-mediated costimulation, was unaffected by Tat101 as was binding to the AP-1 motif in the IL-8 promoter. These experiments identify the CD28RE in the IL-8 promoter as a c-rel recognition site and a Tat101-responsive element. The effect of Tat101 on CD28REs in the IL-8 promoter and the subsequent up-regulation of IL-8 secretion is likely to contribute to the immune dysregulation observed during HIV-1 infection.
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PMID:Superinduction of IL-8 in T cells by HIV-1 Tat protein is mediated through NF-kappaB factors. 951 Jan 90

Dysfunction of cytokine secretion pattern has been suggested to play a central role in the immunopathogenesis of HIV infection. In fact a shift of T helper cell functions from a Th1-type to TH0- or TH2-type has been observed in HIV-1 infected subjects undergoing disease progression. The inhalance of cytokine network is accompanied by persistent activation of the immune system, impaired ability to mount a proper activation response (anergy), and priming to apoptosis. Extensive investigation during the last decade has been conducted on the influence of HIV-1 gp120 or of its precursor gp160 on several lymphocyte and monocyte functions. Gp120 is able to rise intracellular calcium concentration and to induce the formation of inositol triphosphate, can block mitogen- or antigen-driven T cell activation, can induce altered cytokine production by activated PBMC subpopulations, determines impaired cytotoxicity and chemotactic response to antigens, interferes with the activity of antigen presenting cells, enhances or induces apoptosis, stimulates polyclonal B cell activation and induces or up-modulates a number of cytokines, including IL-6. TNF, IL-1-alpha and -beta, IL-10 and IL-8. Furthermore, both IFN-alpha and -gamma, as well as several markers of IFN activity, such as beta 2-microglobulin and neopterin, are induced in gp120-stimulated PBMC. However, neither IL-4 (Th2-type) nor IL-2 (Th1-type), nor DNA synthesis are activated by gp120. On the other hand gp120-stimulated PBMC express increased IL-2 receptors, and can be induced by exogenous IL-2 to proliferate, suggesting that they are in a state of at least partial activation. According to this hypothesis, other activation markers, both early (such as CD69), and late (such as CD45RO and CD71), are induced by gp120, but this even partial activation does not lead to the ability of PBMC to support productive infection by HIV-1, unless in the presence of exogenous IL-2. The HIV-induced cytokines can influence HIV infection either directly, by up- or down-modulating virus replication, or indirectly, by modulating the expression of cellular molecules. In fact, during the budding process, the HIV envelope captures a number of cell membrane proteins, including cytokine receptors such as IL-2R, adhesion molecules such as LFA-1, ICAM-1, -2, HLA Class I and II, as well as cell lineage markers. Gp120-induced cytokines, particularly IFN-gamma, upmodulate the cellular expression of intercellular adhesion molecules, such as ICAM-1. We have shown that the IFN-gamma-driven increase of the expression of ICAM-1 by cells chronically infected with HIV-1 can be transmitted to the virus progeny, resulting in phenotypic alteration of the virus, and leading to the expansion of its host cell spectrum to CD4-negative cells expressing the appropriate ligands, i.e. LFA-1. Intercellular adhesion molecules are also involved in the cell-mediated transmission of HIV infection, and the increased ICAM-1 expression induced by IFN-gamma determines a stimulation of the transmission of HIV from abortively infected endothelial cells to permissive CD4 lymphocytes. On the whole, these data indicate that HIV, or its soluble products such as gp120, can modify several PBMC functions, by inducing a number of cytokines and a partial state of immune activation. It is possible that the gp120-driven changes of PBMC functions are not only an epiphenomenon of HIV infection, but rather, it is likely that they can participate in the immunopathological events responsible for disease progression.
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PMID:Induction of lymphomonocyte activation by HIV-1 glycoprotein gp120. Possible role in AIDS pathogenesis. 960 76

The expression of many cytokines is dysregulated in individuals infected with the human immunodeficiency virus-1 (HIV-1). To determine the effects of HIV-1 infection on cytokine expression in individual cells (at the single cell level), we investigated the intracellular levels of proinflammatory cytokines (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, IL-6, and IL-8) and hematopoietic growth factors (granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF]) in monocyte-derived macrophages, mock-infected, or infected with HIV-1 by immunocytochemical staining for cytokine protein and compared this with secreted cytokine levels as determined by specific enzyme-linked immunosorbent assay (ELISA). No difference in the frequency or intensity of cell-associated immunocytochemical cytokine staining could be observed between HIV-1 and mock-infected cells even though the level of secreted proinflammatory cytokines increased and the hematopoietic growth factors decreased in HIV-1-infected cultures. Furthermore, equal expression of cytokine mRNA was observed in all cells in the culture regardless of whether the cells were productively infected with HIV-1 as determined by double-labelling immunocytochemical staining for HIV-1 p24 antigen and in situ hybridization for cytokine mRNA expression. These results indicate that HIV-1 infection results in dysregulation of intracellular cytokine mRNA expression and cytokine secretion not only in HIV-1-infected cells, but also through an indirect way(s) affecting cells not producing virus.
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PMID:Individual cell analysis of the cytokine repertoire in human immunodeficiency virus-1-infected monocytes/macrophages by a combination of immunocytochemistry and in situ hybridization. 961 74

Inflammatory bowel disease (IBD) and HIV infection can cause diarrhoea which is accompanied by elevated cytokine levels. To elucidate a pathogenic role of cytokines, their effect on ion secretion was studied in human distal colon using the Ussing technique. Interluekin 1beta (IL-1beta) dose dependently increased short-circuit current (ISC). An ISC maximum of 2.5+/-0.3 micromol. h-1.cm-2 was reached at 20 ng/ml within 43+/-4 min. 22Na+ and 36Cl- fluxes were not altered and residual flux increased by 2.4+/-1.0 micromol.h-1.cm-2 indicating that the IL-1beta-induced ISC is based on electrogenic bicarbonate secretion. IL-1beta had no effect on HT-29/B6 epithlial monolayers suggesting that IL-1beta does not act directly on the epithelium. Furthermore, in human colon the effect was not attenuated by removal of the submucosa (total stripping) pointing to a mediation step via subepithlial cells in the lamina propria. While tetrodotoxin and the 5-lipoxygenase inhibitor ICI-230487 had no effect, indomethacin completely blocked IL-1beta action. Prostaglandin determination by RIA revealed an increased production of PGE2. At half maximum effective concentrations an additive action of tumour necrosis factor alpha (TNF-alpha) could be demonstrated on IL-1beta-induced secretion. Interferon alpha (IFN-alpha), IFN-gamma, IL-6, and IL-8 had no seretory effect in human distal colon. None of the investigated cytokines altered the intestinal barrier function. By their secretory effects IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6, and IL-8, may contribute to diarrhoea in IBD and AIDS.
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PMID:IL-1beta and TNF-alpha, but not IFN-alpha, IFN-gamma, IL-6 or IL-8, are secretory mediators in human distal colon. 963 33

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