Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monocytotropic human immunodeficiency virus type 1 (HIV-1) isolates from patients with acquired immunodeficiency syndrome (AIDS) infect mononuclear phagocytes as well as activated T cells, but do not usually infect immature human myeloid cell lines in vitro. The HL-60 promyelocytic/myeloblastic cell line and the promonocytic line, U937, were susceptible to productive infection by monocytotropic HIV-1 isolates (HIV-1JR-FL and HTLV-IIIBa-L) after treatment with retinoic acid, dimethyl sulfoxide, dibutyryl cAMP, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), or 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Virus production was only detected when these compounds were added before virus infection. Virus replication did not correlate with CD4 receptor expression because undifferentiated HL-60 cells express CD4 and the level of CD4 expression did not increase after differentiation in the presence of retinoic acid, 1,25(OH)2D3, or TPA. A mature monocytic cell line (THP-1) was capable of infection without pretreatment, and treatment with differentiating agents enhanced virus production. A chronically infected cell line (J-HL-60) was isolated after HIV-1JR-FL infection of HL-60 cells treated with retinoic acid. Virus production in this cell line was enhanced more than 10-fold after differentiation in the presence of 1,25(OH)2D3 or TPA. The majority of virus production by 1,25(OH)2D3-treated J-HL-60 cells was associated with the mature, adherent population. Molecular analysis of a cloned line of J-HL-60 showed integration of a single DNA provirus. These results suggest that cellular factors associated with precursor cell differentiation along the myelomonocytic pathway are required for optimal replication of monocytotropic HIV-1 strains in vitro.
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PMID:Differentiating agents facilitate infection of myeloid leukemia cell lines by monocytotropic HIV-1 strains. 217 33

Lipopolysaccharide (LPS) potently stimulates human immunodeficiency virus type 1-long terminal repeat (HIV-1-LTR) CAT constructs transfected into monocyte/macrophage-like cell lines but not a T cell line. This effect appears to be mediated through the induction of nuclear factor kappa B (NF-kappa B). Electrophoretic mobility shift assays demonstrate that LPS induces a DNA binding activity indistinguishable from NF-kappa B in U937 and THP-1 cells. LPS is also shown to dramatically increase HIV-1 production from a chronically infected monocyte/macrophage-like cloned cell line, U1, which produces very low levels of HIV-1 at baseline. The stimulation of viral production from this cell line occurs only if these cells are treated with granulocyte/macrophage colony-stimulating factor (GM-CSF) before treatment with LPS. This stimulation of HIV-1 production is correlated with an increase in the level of HIV-1 RNA and and activation of NF-kappa B. LPS is not able to induce HIV-1 production in a cloned T cell line. The effect of LPS on HIV-1 replication occurs at picogram per milliliter concentrations and may be clinically significant in understanding the variability of the natural history of HIV-1 infection.
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PMID:Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression. 219 97

The human cell surface protein CD4 is not only an important accessory molecule in the activation of MHC class-II-restricted T cells, but has also been implicated to be a receptor for the human immunodeficiency virus HIV-I on lymphoid and monocytic cells. We have found that a 24-h treatment of the promonocytic leukemia cell line U937 with rIFN-gamma decreases the expression of the CD4 Ag by 50% as measured by cytofluorographic analysis. The decrease in CD4 expression was dependent on the concentration of rIFN-gamma, with maximal effects occurring at 20 to 200 U/ml. The decrease appeared to be due to actual loss of the CD4 molecule from the cell surface rather than masking of a particular epitope, inasmuch as similar results were obtained with the OKT4 and OKT4A antibodies. The effect of rIFN-gamma to decrease CD4 expression was not due to a general loss of cell surface Ag, because the binding of OKM1 and anti-HLe-1 increased after rIFN-gamma treatment. Treatment of rIFN-gamma also decreased cell surface CD4 expression on the promyelocytic leukemia cell line HL-60, and on the monocytic cell line THP-1, although the extent of the decrease was less than on U937 cells. Freshly isolated normal peripheral blood monocytes treated for 48 h with rIFN-gamma bound much less OKT4 or OKT4A antibody than cells incubated in the absence of rIFN-gamma. Moreover, treatment with rIFN-gamma reduced the percentage of peripheral blood monocytes that were positive for the CD4 Ag. In contrast with the decrease in CD4 levels on rIFN-gamma-treated monocytes, treatment with rIFN-gamma had no effect on CD4 levels on peripheral blood T lymphocytes or T cell lines.
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PMID:Treatment with recombinant IFN-gamma decreases cell surface CD4 levels on peripheral blood monocytes and on myelomonocyte cell lines. 249 48

Prostaglandin E2 is observed at elevated levels during human immunodeficiency virus (HIV) infection and thus may contribute to the HIV-dependent immunosuppression. The mechanisms responsible for this increase are not understood. Evidence indicates that the viral envelope proteins perturb membrane signaling mediated by the CD4 receptor, suggesting that the free envelope protein and/or the intact virus may be responsible for the increase in prostaglandin E2 levels. In this study, we have used THP-1 human monocytes and THP-1 cells differentiated by 12-O-tetradecanoylphorbol-13-acetate treatment into macrophages to determine if the HIV envelope protein, gp120, or an anti-CD4 receptor antibody stimulates prostaglandin formation by interacting with the CD4 receptor. Incubation of THP-1 cells with OKT4A antibody greatly stimulated the CD4-p56lck receptor complex as estimated by enhanced p56lck autophosphorylation, while the gp120 gave small but significant responses. Monocytic THP-1 cells poorly metabolized arachidonic acid to prostaglandin E2 and thromboxane B2 as measured by high-pressure liquid chromatography analysis. Western blot (immunoblot) and Northern (RNA) blot analyses revealed that unstimulated monocytes expressed little prostaglandin H synthase 1 and 2 (PGHS-1 and -2). Incubation of the monocytes with lipopolysaccharide, OKT4A, or gp120 did not increase the formation of prostaglandins. The expression of PGHS-1 or PGHS-2 was also not increased. Differentiation of the monocytes to macrophages by 12-O-tetradecanoylphorbol-13-acetate treatment resulted in increased expression of PGHS-1 and increased formation of prostaglandins compared with that for the monocytes. Lipopolysaccharide stimulation of the macrophages increased the formation of prostaglandins and increased the expression of PGHS-2 in the macrophages. However, OKT4A or gp120 preparation, at concentrations that stimulated p56lck autophosphorylation, did not enhance the formation of prostaglandins or the expression of PGHS-1 or PGHS-2. OKT4A and gp120 also did not stimulate the release of arachidonic acid, indicating that phospholipase A2 was not activated by the CD4 receptor in either the THP-1 monocytes or macrophages. These results indicate that activation of the CD4-p56lck receptor signal transduction pathway by the HIV envelope protein does not increase prostaglandin formation.
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PMID:Human immunodeficiency virus type 1 envelope protein does not stimulate either prostaglandin formation or the expression of prostaglandin H synthase in THP-1 human monocytes/macrophages. 749 15

Because the mechanisms associated with recruitment of monocytes to brain in AIDS encephalitis are unknown, we used tissues from rhesus monkeys infected with simian immunodeficiency virus (SIV) to examine the relative contributions of various adhesion pathways in mediating monocyte adhesion to endothelium from encephalitic brain. Using a modified Stamper and Woodruff tissue adhesion assay, we found that the human monocytic cell lines, THP-1 and U937, and the B cell line, Ramos, preferentially bound to brain vessels from monkeys with AIDS encephalitis. Using a combined tissue adhesion/immunohistochemistry approach, these cells only bound to vessels expressing vascular cell adhesion molecule-1 (VCAM-1). Furthermore, pretreatment of tissues with antibodies to VCAM-1 or cell lines with antibodies to VLA-4 (CD49d) inhibited adhesion by more than 70%. Intercellular adhesion molecule-1 (ICAM-1)/beta 2 integrin interactions were not significant in mediating cell adhesion to the vasculature in encephalitic simian brain using a cell line (JY) capable of binding rhesus monkey ICAM-1. In addition, selectin-mediated interactions did not significantly contribute to cell binding to encephalitic brain as there was no immunohistochemical expression of E-selectin and P-selectin in either normal or encephalitic brain, nor was there a demonstrable adhesive effect from L-selectin using L-selectin-transfected 300.19 cells on simian encephalitic brain. These results demonstrate that using the tissue adhesion assay, THP-1, U937, and Ramos cells bind to vessels in brain from animals with AIDS encephalitis using VCAM-1/alpha 4 beta 1 integrin interactions and suggest that VCAM-1 and VLA-4 may be integral for monocyte recruitment to the central nervous system during the development of AIDS encephalitis.
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PMID:Monocyte adhesion to endothelium in simian immunodeficiency virus-induced AIDS encephalitis is mediated by vascular cell adhesion molecule-1/alpha 4 beta 1 integrin interactions. 750

Macrophage activation resulting from phagocytosis has the potential to modulate human immunodeficiency virus (HIV) replication. We have determined the effects of phagocytosis of particulate stimuli on transcription and release of HIV. Using THP-1 and Mono Mac 6 human monocytic cell lines transfected with HIV long terminal repeat sequence chloramphenicol acetyltransferase (LTR CAT) constructs we have demonstrated that phagocytosis of Mycobacterium tuberculosis enhanced HIV-1 and -2 LTR CAT expression. However phagocytosis of zymosan or inert latex beads had little or no effect on CAT expression. Enhancement of HIV LTR CAT expression was dependent upon intact NF-kappa B binding sites and was independent of tumour necrosis factor alpha secretion. M. tuberculosis strains of different degrees of virulence induced similar levels of enhanced CAT expression. In contrast, phagocytosis of M. tuberculosis by HIV-1-infected THP-1 cells reduced supernatant reverse transcriptase (RT) activity without suppression of p24 antigen release. Phagocytosis of zymosan granules or latex particles did not alter released RT activity. However, phagocytosis of either M. tuberculosis, zymosan granules or latex particles by HIV-1-infected human peripheral blood monocyte-derived macrophages reduced supernatant RT activity. These data indicate that phagocytosis of M. tuberculosis may enhance HIV transcription in monocytic cells although it may reduce release of intact HIV.
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PMID:Phagocytosis of Mycobacterium tuberculosis modulates human immunodeficiency virus replication in human monocytic cells. 751 19

Macrophage adherence, an important regulatory signal, has the potential to affect human immunodeficiency virus (HIV) production either directly or by priming monocytes to respond to other activating signals. We have investigated the role of adherence as an activator of HIV-1 transcription and release. The effects of adherence on HIV-1 transcription were examined by using THP-1 cells, a human monocytic cell line, transfected with HIV long terminal repeat (LTR)-chloramphenicol acetyltransferase (CAT) constructs. The effects of adherence on release of HIV-1 were investigated in both HIV-1-infected THP-1 cells and human peripheral blood monocyte-derived macrophages (MDM). Adherence of lipopolysaccharide (LPS)-stimulated THP-1 cells to either tissue culture plastic or endothelial cells was crucial for enhanced HIV-1 transcription as measured by LTR-CAT expression. Such increased LTR-CAT expression did not occur with an HIV LTR construct containing mutated NF-kappa B binding sites. In contrast, release of whole HIV, measured by reverse transcriptase (RT) activity in tissue culture medium, was reduced upon adherence of stimulated HIV-1-infected THP-1 cells without suppression of HIV LTR-CAT transcription or p24 release. This finding suggested that activation of adherent monocytic cells interfered with HIV assembly and release. Although the reduction of RT activity following activation of HIV-1-infected MDM was independent of adhesion, adherence alone of nonstimulated HIV-infected MDM to endothelial cells was sufficient to induce a reduction in RT release. This study demonstrates that LPS stimulation of monocytic cells enhances HIV LTR transcription under adherent conditions. In contrast, activation of adherent monocytic cells infected with HIV reduced viral release.
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PMID:Release of human immunodeficiency virus by THP-1 cells and human macrophages is regulated by cellular adherence and activation. 768 70

Phagocytosis of Mycobacterium tuberculosis by human monocytes or macrophages is classically followed by granuloma formation in vivo. Granuloma are comprised of cells of the monocyte lineage together, in many instances, with antigen-specific T lymphocytes. Development of granuloma depends upon recruitment of both cell types, but recruitment of monocytes is pivotal as these cells secrete anti-mycobacterial cytokines and IL-8, a T cell chemoattractant. We have therefore investigated gene regulation of Monocyte Chemotactic Protein 1 (MCP-1), an important monocyte chemotactic cytokine, following phagocytosis of particulate material (latex beads and zymosan) and live M. tuberculosis by two human monocytic cell lines. In THP-1 cells and phenotypically more differentiated Mono Mac 6 cells, MCP-1 mRNA accumulation was first detectable by Northern analysis of 4 hours and increased over 24 hours. Magnitude and kinetics of MCP-1 gene expression was independent of the biochemical nature of the phagocytic stimulus, M. tuberculosis strain virulence or pre-treatment with anti-TNF. In contrast to the uniform effect of different phagocytic stimuli on MCP-1 gene expression, we have shown that M. tuberculosis but not latex or zymosan, increased IL-8 gene expression, a chemotactic agent for T cells. In additional experiments with THP-1 cells infected with human immunodeficiency virus (HIV), viral infection did not alter MCP-1 gene expression following phagocytosis. MCP-1 gene expression appears to be a conserved antigen-independent response of human monocytic cells which is activated following particulate phagocytosis. MCP-1 gene expression may thus be involved in recruitment of monocytes during granuloma formation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phagocytosis of Mycobacterium tuberculosis or particulate stimuli by human monocytic cells induces equivalent monocyte chemotactic protein-1 gene expression. 768 73

Tuberculosis has emerged as an epidemic fueled by the large number of individuals infected with the human immunodeficiency virus, especially those who are injecting drug users. We found a striking increase from 4- to 208-fold in p24 levels in bronchoalveolar lavage fluid from involved sites of Mycobacterium tuberculosis infection vs uninvolved sites in three HIV+ patients. We used an in vitro cell culture model to determine if tuberculosis could activate replication of HIV-1. Mononuclear phagocyte cell lines U937 and THP-1 infected with HIV-1JR-CSF, in vitro and stimulated with live M. tuberculosis H37Ra, had a threefold increase in p24 in culture supernatants. Using the HIV-1 long terminal repeat with a chloramphenicol acetyltransferase (CAT) reporter construct, live M. tuberculosis increased transcription 20-fold in THP-1 cells, and cell wall components stimulated CAT expression to a lesser extent. The nuclear factor-kappa B enhancer element was responsible for the majority of the increased CAT activity although two upstream nuclear factor-IL6 sites may also contribute to enhanced transcription. Antibodies to TNF-alpha and IL-1 inhibited the increase in CAT activity of the HIV-1 long terminal repeat by M. tuberculosis from 21-fold to 8-fold. Stimulation of HIV-1 replication by M. tuberculosis may exacerbate dysfunction of the host immune response in dually infected individuals.
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PMID:Mycobacterium tuberculosis enhances human immunodeficiency virus-1 replication by transcriptional activation at the long terminal repeat. 773 95

Cellular adherence is important for monocyte migration and function and is known to induce monocyte activation, leading to the production of mRNA for several proto-oncogenes and cytokines. In addition, since cellular adherence has important intracellular signalling function, it has the potential to enhance human immunodeficiency virus (HIV) replication in monocytic cells. We have investigated the effects of adhesion of the monocytic cell line THP-1 transfected with HIV1 or HIV2 long terminal repeat chloramphenicol acetyltransferase (LTR CAT) constructs. These studies have shown that adherence to tissue culture plastic or confluent endothelial cells is essential for enhanced HIV LTR CAT expression in lipopolysaccharide-stimulated cells. In addition, we have investigated the effects of engagement of specific adhesion molecules, using immobilized antibodies, on HIV replication in the promonocytic cell line OM101, which contains a single latent proviral copy of HIV. Such studies have demonstrated that engagement of CD18, the beta subunit of the lymphocyte function-related antigen-1 (LFA-1) and major histocompatibility complex class II (MHC II) enhanced HIV replication. LFA-1 is involved in both monocyte-endothelial cell interactions and monocyte-T-cell interactions, and MHC II is involved in monocyte interaction with antigen-specific T cells. These data suggest that such interactions of membrane adhesion molecules with their appropriate ligand enhance HIV replication in vivo. Thus, this study has demonstrated that cellular adherence is a key regulatory factor of HIV replication in monocytic cells.
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PMID:Cellular adherence enhances HIV replication in monocytic cells. 780 Sep 38


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