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)

An investigation was undertaken to determine whether a recombinant gp160 envelope protein, which is currently being evaluated as a vaccine for AIDS, induces or modulates the production of tumour necrosis factor-alpha (TNF-alpha) or interleukin-1 beta (IL-1 beta). Incubation of monocytes from healthy, HIV-seronegative persons with 0.0001-1.0 micrograms of the recombinant vaccine did not result in the secretion of TNF-alpha or IL-1 beta, nor did the recombinant product augment or suppress monokine production by lipopolysaccharide (LPS) stimulated monocytes. The vaccine was also without a stimulatory or modulatory effect upon TNF-alpha or IL-1 beta secretion by monocytes from a patient with the AIDS-related complex (ARC) and from the monocytic THP-1 cell line. The lack of effect of gp160 on monokine production has important implications for its efficacy as a vaccine for AIDS.
 ...
PMID:Effect of a recombinant HIV gp160 vaccine on monokine production. 199 54

Nuclear factor kappa B (NF-kappa B) is a ubiquitous transcription factor that affects expression of many genes, including immunoglobulin kappa (kappa), the interleukin-2 receptor alpha chain, and two genes in HIV-1. NF-kappa B can be activated by a number of stimuli, including pharmacological stimulation of protein kinase C by phorbol 12-myristate 13-acetate (PMA) and treatment in vitro with either protein kinase C or protein kinase A. This has lead to the proposal that these kinases are key enzymes in the physiological activation of NF-kappa B as well. We have used a murine B cell line, 70Z/3, and T cell line, EL-4 6.1 C10, to study the activation of NF-kappa B by two physiological activators, interleukin-1 alpha (IL-1) and lipopolysaccharide (LPS). There are four reasons to propose that these agents activate pathways that do not include protein kinase C as a major component in these cell lines. First, the protein kinase C inhibitor 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7) strongly inhibited PMA-induced activation of NF-kappa B in 70Z/3 cells but had no effect on NF-kappa B activated by IL-1 or LPS. Second, depletion of protein kinase C by prolonged growth of 70Z/3 in PMA abrogated the capacity of the cells to activate NF-kappa B in response to further PMA treatment. However, these same cells activated NF-kappa B normally after either IL-1 or LPS treatment. Third, IL-1 effectively activated NF-kappa B in EL-4 6.1 C10 cells, but PMA did not. Fourth, interferon-gamma is a potent activator of protein kinase C in 70Z/3 cells, but is completely inactive in the mobilization of NF-kappa B. These results suggest that the physiological inducers IL-1 and LPS activate NF-kappa B by pathways independent of protein kinase C in both 70Z/3 and EL-4 6.1 C10 cells.
 ...
PMID:Evidence that interleukin-1 and phorbol esters activate NF-kappa B by different pathways: role of protein kinase C. 205 61

We studied functional and immunohistochemical characteristics of cultured rat microglia. Unstimulated microglia did not proliferate. Microglia stimulated with LCM (L929 conditioned medium: colony stimulating factor-1) had proliferative activity and increased acid phosphatase activity. LPS (lipopolysaccharide) and IFN gamma (interferon-gamma) but did not affect proliferative activity. Immunohistochemically, RCA-1 lectin and GS-1 lectin, which react to beta-D-galactose and alpha-D-galactose respectively, strongly reacted to the cytoplasm and membrane of unstimulated microglia. After stimulation with LCM, microglia elongated processes and decreased response to these lectins. On the other hand, microglia stimulated with LCM showed increased reactivity to monoclonal antibody of vimentin. Microglia stimulated with LPS had round shape and had response to these lectins and vimentin. Microglia stimulated with IFN gamma had adhesive activity and weakly stained with these lectins but not with vimentin. ED-1 (monoclonal antibody of rat monocytes/macrophages) reacted to unstimulated and stimulated microglia. In flow cytometry, unstimulated microglia expressed OX-18 (MHC class I) and W3/25 (CD4) antigen. After stimulation with IFN gamma, microglia were induced to express these antigens. CD4 antigen is a marker of helper/inducer T cells and thought to be a receptor of HIV. The results that microglia had CD4 antigen which was further induced with IFN gamma are important to investigate infection of the CNS with HIV. OX-6 (Ia) antigen was induced with IFN gamma. This indicates that the microglia plays a central role in the CNS immune reaction. These characteristics of cultured rat microglia provide useful informations to investigate the pathogenesis of the CNS disorders.
 ...
PMID:[Functional and immunohistochemical studies of cultured rat microglia]. 206 Feb 34

Hydrogen peroxide and oxygen radicals are agents commonly produced during inflammatory processes. In this study, we show that micromolar concentrations of H2O2 can induce the expression and replication of HIV-1 in a human T cell line. The effect is mediated by the NF-kappa B transcription factor which is potently and rapidly activated by an H2O2 treatment of cells from its inactive cytoplasmic form. N-acetyl-L-cysteine (NAC), a well characterized antioxidant which counteracts the effects of reactive oxygen intermediates (ROI) in living cells, prevented the activation of NF-kappa B by H2O2. NAC and other thiol compounds also blocked the activation of NF-kappa B by cycloheximide, double-stranded RNA, calcium ionophore, TNF-alpha, active phorbol ester, interleukin-1, lipopolysaccharide and lectin. This suggests that diverse agents thought to activate NF-kappa B by distinct intracellular pathways might all act through a common mechanism involving the synthesis of ROI. ROI appear to serve as messengers mediating directly or indirectly the release of the inhibitory subunit I kappa B from NF-kappa B.
 ...
PMID:Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. 206 63

This review suggests that infections are potent immunomodulators by causing significant alterations in one or more mediators of homeostasis and that an effective antibiosis may be a potent immunomodulator, albeit indirectly. When large numbers of microorganisms are killed, their enzymes and toxins are rapidly released and activate the immune system. The septic syndrome and the potentially progressive states of septic shock, acute respiratory distress syndrome and multiple organ system failure illustrate the biological response modulating (BRM) activity of both infection and antibiotic. Enhancement of phagocytosis and intracellular killing would be a useful immunomodulatory activity for antibiotics. Equally useful would be the capacity of the antibiotic to bind or inactivate bacterial lipopolysaccharide (LPS) to diminish monocyte release of tumour-necrosing factor (TNF) at a rate equal to or faster than the killing effect of the antibiotic on bacteria. For other types of immune deficiencies, such as are observed in HIV-positive patients with secondary bacterial, fungal and viral infections, modulation of viral receptors including HIV-R on CD4 lymphocytes accompanied by their up-regulation, enhancement of interferon (IFN) and natural killer (NK) function and inhibition of CD8 suppressor activity would be important activities. The classic example of polymyxin as an immunomodulating, albeit toxic, antibiotic offers a rational and definitive basis for the concept. In-vitro data on cefodizime, a third generation cephalosporin that achieves good tissue levels, are presented and show the ability of the intact antibiotic, as well as its immunomodulating side-chain, to down-regulate TNF and interleukin 1 (IL-1) released from human monocytes by lectin-activated lymphocytes, LPS and IFN.
 ...
PMID:Antibiotics as biological response modifiers. 207 50

Macrophages, unlike CD4+ T cells, can be productively infected by human immunodeficiency virus (HIV) without prior cellular activation. Cytopathic infection ensues without the induction of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), or tissue factor genes. In detailed studies on TNF alpha, HIV infection did not affect the regulation of TNF alpha in response to bacterial lipopolysaccharide. In an effort to examine the interferon responsiveness of HIV-infected macrophages, the cells were challenged with vesicular stomatitis virus (VSV) with or without interferon pretreatment. Surprisingly, HIV-infected macrophages were completely resistant to VSV-induced lysis even in the absence of interferon; however, no interferon was detected in the supernatants of these infected cells. The resistance of HIV-infected macrophages to superinfection with VSV indicates a previously undescribed effect of HIV upon macrophage cellular metabolism.
 ...
PMID:Characterization of a macrophage-tropic HIV strain that does not alter macrophage cytokine production yet protects macrophages from superinfection by vesicular stomatitis virus. 217 98

Phagocytic macrophages are known to support noncytopathic, chronic infections of human immunodeficiency virus (HIV). Regulation of viral replication in such cells with either chronic low-grade or latent HIV infection is probably influenced by both viral and cellular factors acting on the viral long terminal repeat (LTR). This study identifies naturally occurring biological response modifiers which are able to affect the HIV-LTR linked to the chloramphenicol acetyl transferase (LTR-CAT) gene in a stable transfection of the human promonocyte cell line, U937, in the absence of other viral proteins. In this model system, endotoxin lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha) are able to independently stimulate expression of LTR-CAT. Granulocyte/macrophage-colony-stimulating factor can enhance the effect of TNF-alpha or LPS, but other cytokines tested had minimal or no effect on LTR-CAT. In addition to effects on cellular susceptibility and immune function, the ability of naturally occurring factors to affect HIV-LTR in its integrated state may have particular relevance to progression of active disease from latent infection.
 ...
PMID:Expression of human immunodeficiency virus long terminal repeat in the human promonocyte cell line U937: effect of endotoxin and cytokines. 220 Jun 14

Human promonocytic cells chronically infected with human immunodeficiency virus-1 (HIV-1) (clone U1.1.5) were grown in the presence of media conditioned by primary rat cortical astrocytes and HIV-1 expression was assessed by measuring reverse transcriptase activity. Media conditioned by non-stimulated and lipopolysaccharide (LPS)-stimulated astrocytes induced the expression of HIV-1 2.1-fold and 4.1-fold, respectively. LPS alone, media conditioned by the uninfected parental cell line of U1.1.5 (U937), and culture media from four other cell lines, had no effect on viral expression. The magnitude of induction was time- and dose-dependent. Tumor necrosis factor alpha (TNF-alpha) was detected in LPS-stimulated astrocyte-conditioned medium and the HIV-inducing capability of the medium was neutralized, in part, by an antibody to recombinant murine TNF-alpha. These results suggest a role for astrocytes in the induction of HIV expression and thus in the pathogenesis of HIV-1 infection in brain.
 ...
PMID:Astrocyte-conditioned medium stimulates HIV-1 expression in a chronically infected promonocyte clone. 222 7

2',3'-Dideoxyadenosine (ddA) is a nucleoside analogue with anti-HIV activity and one of its metabolic products, 2',3'-dideoxyinosine (ddI), has shown promising results in clinical trials for the treatment of acquired immunodeficiency syndrome (AIDS). Because AIDS viruses target the immune system, it is important to understand the potential effects of anti-AIDS drugs, including natural nucleosides, on the immune system. Previous immunotoxicological studies have shown that 22 treatments with ddA to female B6C3F1 mice over a period of 30 days had no effect on cell-mediated immunity, including the mixed lymphocyte reaction and response to mitogenic signals, but suppressed in vitro IgM plaque-forming cell (PFC) response to sheep red blood cells. The present studies show that suppression of the IgM PFC response was dose dependent with a 96% reduction in IgM PFCs/10(6) spleen cells at the highest dose (350 mg/kg). The in vivo IgM PFC response to DNP-Ficoll and the in vitro IgM PFC response to lipopolysaccharide, both T-independent antigens, were also suppressed in the spleens of ddA-treated mice. The analysis of splenocyte subtypes shows no change in the percentage of B cells (surface immunoglobulin positive cells), T helper cells (L3T4 positive cells), and T suppressor cells or T cytotoxic cells (Lyt-2 positive cells) in the spleens of ddA-treated mice. In vitro separation and reconstitution studies in which the IgM PFC response was monitored indicated that the B lymphocyte rather than the T lymphocyte or antigen-presenting cell is the primary cell targeted by ddA. This information provides a data base for further mechanistic study and may reflect on the clinical use of other nucleoside analogues, e.g., ddI by providing the clinician with information indicating the potential decrease in humoral immunity.
 ...
PMID:The B lymphocyte is the immune cell target for 2',3'-dideoxyadenosine. 223 21

A promonocytic cell model was used to investigate cytokine gene transcription in U937 and U9-IIIB cells chronically infected with human immunodeficiency virus type 1 (HIV-1). The production of interferon (alpha-1 interferon [IFN-alpha 1], IFN-alpha 2, and IFN-beta), interleukin (interleukin 1 alpha [IL-1 alpha], IL-1 beta, and IL-6), and tumor necrosis factor alpha (TNF-alpha) mRNA was characterized by quantitative polymerase chain reaction mRNA phenotyping in U937 and U9-IIIB cells following coinfection with Sendai paramyxovirus or stimulation with lipopolysaccharide (LPS). Chronic HIV-1 infection of U9-IIIB cells resulted in a low constitutive level of transcription of TNF and IL-1 genes but not IFN genes; however, when the cells were coinfected with Sendai virus, 10- to 20-fold higher levels of IFN-beta, IL-1 beta, IL-6, and TNF-alpha mRNA were observed in U9-IIIB cells than in similarly induced U937 cells. The enhanced levels of cytokine RNA in virus-infected U9-IIIB cells were also accompanied by higher levels of IFN antiviral activity and TNF secretion than in U937 cells. Transcript levels for IFN-alpha 1 and IFN-alpha 2 were equivalently induced in virus-infected U937 and U9-IIIB cells, indicating that a generalized derepression of cytokine gene expression did not occur as a consequence of HIV-1 infection. When LPS was used as an inducer, a distinct pattern of cytokine gene expression was detected in U9-IIIB cells. TNF-alpha and IL-1 beta but not IFN-alpha or IFN-beta transcripts were induced by LPS. These results suggest that HIV-1 infection of promonocytic cells may prime or sensitize cells such that subsequent antigenic challenge leads to coordinate enhancement of cytokine gene expression.
 ...
PMID:Coordinate enhancement of cytokine gene expression in human immunodeficiency virus type 1-infected promonocytic cells. 224 88


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