Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.7.49 (reverse transcriptase)
31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The pleiotropic immunoregulatory cytokine transforming growth factor beta (TGF-beta) potently suppresses production of the human immunodeficiency virus (HIV), the causative agent of the acquired immunodeficiency syndrome, in the chronically infected promonocytic cell line U1. TGF-beta significantly (50-90%) inhibited HIV reverse transcriptase production and synthesis of viral proteins in U1 cells stimulated with phorbol myristate acetate (PMA) or interleukin 6 (IL-6). Furthermore, TGF-beta suppressed PMA induction of HIV transcription in U1 cells. In contrast, TGF-beta did not significantly affect the expression of HIV induced by tumor necrosis factor alpha (TNF-alpha). These suppressive effects were not mediated via the induction of interferon alpha (IFN-alpha). TGF-beta also suppressed HIV replication in primary monocyte-derived macrophages infected in vitro, both in the absence of exogenous cytokines and in IL-6-stimulated cultures. In contrast, no significant effects of TGF-beta were observed in either a chronically infected T cell line (ACH-2) or in primary T cell blasts infected in vitro. Therefore, TGF-beta may play a potentially important role as a negative regulator of HIV expression in infected monocytes or tissue macrophages in infected individuals.
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PMID:Transforming growth factor beta suppresses human immunodeficiency virus expression and replication in infected cells of the monocyte/macrophage lineage. 170 78

Although an autocrine growth mechanism through interleukin 6 has been advocated in human myeloma cells, reports of IL-6 production by cells from established myeloma cell lines are rare. In the present study, we examined whether or not a minute amount of interleukin 6 is produced in 4 human myeloma cell lines. IL-6 production was not detected in any of the 4 lines by enzyme immunoassay, bioassay with two interleukin 6-dependent murine hybridoma cell lines and Northern hybridization. However, we detected interleukin 6 mRNA in one (U266) of the 4 lines by the reverse transcriptase-polymerase chain reaction. Nevertheless, the proliferation of all 4 lines was not inhibited by an anti-interleukin 6 antibody. These results suggest that autocrine stimulation by interleukin 6 is not involved in the majority of human myeloma cell lines.
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PMID:Estimation of interleukin 6 production by reverse transcriptase-polymerase chain reaction in four human myeloma cell lines. 172 Apr 89

The aim of this study was to investigate mechanisms of anti-tumour activity and necrosis induced by combinations of tumour necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma). In a breast cancer xenograft model, locally injected recombinant human TNF-alpha arrested growth of established tumours in the absence of overt necrosis. Macroscopic necrosis occurred when rat IFN-gamma, which had no anti-tumour activity as a single agent, was given systemically. Treatment with TNF-alpha and IFN-gamma caused focal engorgement of tumour capillaries with erythrocytes, intravascular recruitment of polymorphonuclear cells and platelet adherence to the tumour vascular endothelium 4 h after the combined treatment. This was followed by destruction of tumour vascular endothelium and both necrosis and apoptosis of tumour cells. Concomitant with these changes, semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the increase of stromal (murine) mRNA levels for TNF-alpha, TNF receptor 55 kDa, TNF receptor 75 kDa, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, P-selectin and interleukin 6 (IL-6). Thus, the effect of the combined TNF-alpha and IFN-gamma therapy involved the selective destruction of the tumour vasculature, death of tumour cells and increased expression of a series of stromal cytokines, cytokine receptors and adhesion molecules, which could be implicated in the observed events.
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PMID:Changes in endogenous cytokines, adhesion molecules and platelets during cytokine-induced tumour necrosis. 757 63

The effects of cysteamine (2-aminoethanethiol, MEA) and its disulfide, cystamine, on the human immunodeficiency virus (HIV-1) expression in chronically infected promonocytic cells (U1), T cell line (ACH-2), and peripheral blood monocyte-derived macrophages (MDM) were investigated. U1 and ACH-2 cells constitutively express low levels of virus, which is increased by the addition of tumor necrosis factor (TNF-alpha), interleukin 6 (IL-6), granulocyte-macrophage-colony-stimulating factor (GM-CSF), and other inducers. Cystamine, in noncytotoxic doses, suppressed in a concentration-dependent fashion the induction of HIV-1 expression mediated by TNF-alpha, IL-6, GM-CSF, and monokine-enriched monocyte culture supernatants in both U1 and ACH-2 cells as determined by HIV-1 reverse transcriptase (RT) activity. Similarly, HIV-1 expression was substantially reduced in the cystamine-treated primary MDM cultures compared with the untreated control cultures. The addition of cystamine into HIV-1 chronically infected MDM (12 days after infection was established) also suppressed 80-90% of RT activity in comparison to the untreated controls. HIV-1 (Bal) infected MDM cultures (without cystamine treatment) demonstrated giant syncytium formation, whereas cystamine-treated cultures lacked the giant syncytia induced by HIV-1 infection. Cystamine also inhibited LPS-induced TNF production in MDM. In contrast to cystamine, cysteamine showed no significant effects on either the monokine-induced HIV-1 expression in U1 or ACH-2 or acute and chronic HIV-1 infection in MDM.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cystamine inhibits HIV type 1 replication in cells of monocyte/macrophage and T cell lineages. 763 61

Gene amplification by reverse transcriptase PCR with heterologous primers has been used to obtain a cDNA clone encoding the structural sequences of ovine interleukin 6 from alveolar macrophages. This cDNA encodes a protein of M(r) = 23,429, which is 53% homologous in amino acid sequence to human IL = 6. The clone hybridizes to an RNA of size 1260 nt in alveolar macrophages, expression of which is potentiated by LPS. The ovine IL-6 structural gene has been cloned into the yeast expression vector pOGS40, and used to produce a recombinant protein. This protein is capable of causing increased immunoglobulin production in pokeweed mitogen stimulated ovine peripheral blood mononuclear cells at concentrations of 10-100 ng/ml, but it only causes very limited replication of B9 cells, a murine IL-6 dependent cell line. This is in contrast to recombinant human IL-6, which is capable of stimulating B9 cell proliferation, but not immunoglobulin production by ovine PBMC.
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PMID:Cloning, sequencing and expression of the ovine interleukin 6 gene. 764 Mar 42

A platelet-activating factor antagonist, RP 55778, potently suppressed the induction of human immunodeficiency virus (HIV) expression in chronically infected promonocytic U1 cells. RP 55778 inhibited the production of reverse transcriptase activity in U1 cells stimulated with the transcriptionally active inducers of virus production, tumor necrosis factor alpha and phorbol 12-myristate 13-acetate. This effect was correlated only in part with a reduction in the levels of HIV RNA, suggesting that this agent was also affecting posttranscriptional levels of virus production. In this regard, RP 55778 effectively blocked the induction of HIV expression in U1 cells stimulated with interleukin 6 and granulocyte-macrophage colony-stimulating factor, which act predominantly as posttranscriptional activators of HIV expression. Finally, RP 55778 inhibited the production of endogenous tumor necrosis factor alpha in phorbol 12-myristate 13-acetate-stimulated cells, thereby interfering with an autocrine pathway of virus expression. The suppressive effects of RP 55778 on HIV expression appeared to be independent of the platelet-activating factor cell surface receptor on U1 cells. RP 55778 inhibited acute HIV replication in primary T-cell blasts and the proliferative capacity of these cells. This study suggests that RP 55778 may represent potentially useful compounds in the treatment of HIV infection.
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PMID:A platelet-activating factor antagonist, RP 55778, inhibits cytokine-dependent induction of human immunodeficiency virus expression in chronically infected promonocytic cells. 768 1

The pro-inflammatory molecules, tumor necrosis factor alpha (TNF alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and prostaglandin E2 (PGE2), are postulated to have a role in human pregnancy and parturition. The ability of interleukin 4 (IL-4) to suppress the production of TNF alpha, IL-1, IL-6, and PGE2 by activated monocytes prompted us to investigate a possible regulatory role for IL-4 in human gestation. Immunohistochemical techniques were used to show that human amnion epithelium stained positively for IL-4. Tissue from both the first (n = 5) and third (n = 46) trimester expressed immunoreactive IL-4, which was detected by the use of four antihuman IL-4 monoclonal antibodies. Analysis of mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR) on RNA extracts of amnion epithelial cells indicated that they were the source of IL-4. One of the anti-IL-4 antibodies used stained IL-4 protein associated with the basement membrane of the amnion epithelium. The mechanism of this association was investigated. IL-4 was shown to be a heparin-binding cytokine, which would enable it to bind to components of the extracellular matrix. Thus, this study identified a previously undescribed cellular source of IL-4, implicating a role for IL-4 in human gestation. Additionally, glycosaminoglycan binding may regulate IL-4 activity in vivo.
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PMID:Interleukin 4 production by human amnion epithelial cells and regulation of its activity by glycosaminoglycan binding. 778 6

When administered as single agents, both interferon gamma (IFN-gamma) and interleukin 6 (IL-6) significantly increase carcinoembryonic antigen (CEA) and HLA class I antigen expression on the surface of human colorectal tumour cells. Studies were carried out to determine whether by combining those cytokines a synergistic enhancement of CEA and HLA expression could result. The findings revealed that the administration of 20 units IFN-gamma along with 1.7 ng IL-6, concentrations of each cytokine that individually induced minimal antigenic changes, together synergistically increased CEA and HLA class I as well as induced qualitative changes in HLA expression on WiDr human colon carcinoma cells. The magnitude of the synergistic increases in CEA and HLA class I expression were reminiscent of the level of antigen augmentation observed when administering 20- to 100-fold higher amounts of each cytokine as a single agent. Also, the addition of IL-6 potentiated the IFN-gamma induction of HLA class II expression. The combined administration of IL-6 potentiated the IFN-gamma did not have any additive or synergistic effects on the growth suppression of those tumour cells. Interestingly, utilization of specific neutralizing antibodies for type I interferons abrogated the increases of CEA and HLA expression seen with IL-6 treatment alone or in combination with IFN-gamma. Moreover, reverse transcriptase/polymerase chain reaction analyses revealed a constitutive expression as well as a temporal increase of IFN-beta mRNA transcripts in colon tumour cells treated with IL-6. Therefore, the findings provide indirect evidence that IFN-beta production seems to play a critical role in the ability of IL-6 to upregulate antigen expression alone or in combination with IFN-gamma. These findings provide insight into cytokine combinations that synergistically upregulate tumour-associated and normal HLA antigen expression on the surface of human tumour cells. Those results provide the rationale for the combined use of such cytokines to heighten tumour cell recognition in monoclonal antibody- or cell-mediated-based immunotherapeutic approaches.
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PMID:Synergistic effects of IL-6 and IFN-gamma on carcinoembryonic antigen (CEA) and HLA expression by human colorectal carcinoma cells: role for endogenous IFN-beta. 778 31

8701-BC is a recently characterized cell line isolated from a primary ductal infiltrating carcinoma of the breast (d.i.c.), showing some pleomorphism in cell microanatomy at an ultrastructural level. We have obtained different sublines of 8701-BC cells by cloning in soft agar at different concentrations (0.3% and 0.6%), and we have characterized the cloned lines by some morphological and growth parameters. 8701-BC cells and clones have been submitted to analysis by reverse transcriptase-linked polymerase chain reaction to detect mRNAs of various cytokines (transforming growth factor-beta s, tumour necrosis factors, interleukin 1s, interleukin 6, parathyroid hormone-related peptide, gamma interferon) and of urokinase, which are bioactive molecules commonly involved in cell-cell and cell-stroma interactions at primary and/or secondary sites of invasion. The aims of the present investigation were to determine: (a) if the corresponding genes are active in 8701-BC cell line and (b) if the sublines tested exhibit transcriptional heterogeneity. The results obtained show that 8701-BC cells express transcripts of transforming growth factor-beta s, urokinase and parathyroid hormone-related peptide (PTHrP), the latter product being responsible for the cancer-associated humoral hypercalcemic syndrome. Moreover, while the first two mRNAs are detectable in all the sublines tested, PTHrP is expressed almost uniquely by the clones isolated in 0.6% agar which exhibit a peculiar morphological appearance, a higher growth rate and a more active invasive behaviour in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Transforming growth factor-beta 1, beta 2, and beta 3, urokinase and parathyroid hormone-related peptide expression in 8701-BC breast cancer cells and clones. 829 80

In a recent study, antioxidant therapy at the time of renal transplantation in humans was associated with fewer rejection episodes and extended graft survival. A hypothesis generated by such studies and based on the response-to-injury model is that reducing the oxidative injury during transplantation may dampen certain cellular responses to injury that are important in triggering allograft rejection. To test whether ablation of oxidative injury would limit such responses, kidneys were transplanted between Wistar-Furth rats, with and without antioxidant 21-aminosteroid. 21-Aminosteroid was administered before kidney harvest and, again, before transplant reperfusion. The recipient's left kidneys, removed to accommodate the donor kidneys, were used as normal control. The removal of the right kidneys contralateral to the transplant were delayed to day 4 to provide interim renal support. The transplanted kidneys were harvested on day 7. Administration of 21-aminosteroid was associated with better graft function and reduced lipid peroxidation. Compared with the normal control kidneys, the kidneys transplanted with vehicle had higher cytokine mRNA levels (measured by reverse transcriptase-polymerase chain reaction) for interleukin 2, interleukin 6, tumor necrosis factor-alpha, and interferon-gamma. The levels for these cytokines were reduced in kidneys transplanted with 21-aminosteroid. An increase in inducible nitric oxide synthase mRNA in the transplanted kidney was inhibited by 21-aminosteroid, as were the increase in class I and II MHC antigens. The new finding, that a reduction in transplantation-related oxidative injury in a syngeneic model is accompanied by a reduction in the expression of cytokines, MHC antigens, and inducible nitric oxide synthase, provides partial support for the response-to-injury hypothesis in the setting of renal transplantation. The data also demonstrate for the first time the efficacy of 21-aminosteroid to reduce lipid peroxidation and renal injury in kidneys transplanted after cold preservation.
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PMID:Antioxidant lazaroid U-74006F improves renal function and reduces the expression of cytokines, inducible nitric oxide synthase, and MHC antigens in a syngeneic renal transplant model. Partial support for the response-to-injury hypothesis. 897 Jun 19


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