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)

Human immunodeficiency virus type 1 (HIV-1) infection is associated with elevated levels of inflammatory cytokines in the serum and cerebrospinal fluid of infected persons, but the sources of these proteins as well as the specific stimuli which trigger their production and release have not been fully defined. In this study, we evaluated the ability of HIV-1-specific cytotoxic T-lymphocyte (CTL) clones derived from seropositive persons to release gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and TNF-beta upon contact with target cells presenting viral antigen. Peripheral blood- and cerebrospinal fluid-derived HIV-1-specific CD3+ CD4- CD8+ CTL clones as well as freshly isolated peripheral blood mononuclear cells from infected persons were tested in parallel for HIV-1-specific cytotoxicity and cytokine release. Target cells consisted of autologous and allogeneic B-lymphoblastoid cell lines sensitized with synthetic HIV-1 peptides containing the epitopes recognized by these CTL. Cytokine production was measured by specific enzyme-linked immunosorbent assay of culture supernatant fluid. HIV-1-specific CTL clones directed at envelope, Gag, reverse transcriptase, and Nef epitopes specifically released IFN-gamma, TNF-alpha, and TNF-beta upon contact with their relevant target epitopes but not following contact with irrelevant epitopes. These cytokines were released in an HLA class I-restricted fashion, and release was detectable as early as 4 to 6 h of incubation and remained elevated at 48 h. Fresh peripheral blood mononuclear cells from a seropositive person likewise released IFN-gamma in an antigen-specific and HLA class I-restricted manner when incubated with target cells presenting a peptide containing a CTL epitope, paralleling the HIV-specific cytolytic activity of these cells. These studies indicate that in addition to mediating direct cytotoxicity, HIV-1-specific CTL may affect other immune responses by releasing IFN-gamma, TNF-alpha, and TNF-beta. Elevated levels of these cytokines which have been detected in serum and cerebrospinal fluid of infected persons may be due at least in part to the persistent HIV-1-specific CTL response.
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PMID:Human immunodeficiency virus type 1-specific cytotoxic T lymphocytes release gamma interferon, tumor necrosis factor alpha (TNF-alpha), and TNF-beta when they encounter their target antigens. 768 29

Reactive oxygen species like hydrogen peroxide (H2O2) have been shown to serve as messengers in the induction of NF-kappa B and then in the activation and replication of HIV-1 in human cells. Because singlet oxygen (1O2) is another very important reactive oxygen species whose action in transcription factor activation is totally undetermined, we started to investigate its role in both NF-kappa B and HIV-1 activation. For provoking unbalanced redox conditions, 1O2 was generated by photosensitization using methylene blue as photosensitizer. Lymphocytes or monocytes (ACH-2 or U1 respectively) latently infected with HIV-1 were treated by photosensitization mediated by methylene blue and the production of reactive oxygen species was monitored through their cytotoxic effect in infected cells. The generation of 1O2 by methylene blue turns out to be very efficient in inducing NF-kappa B as a heterodimer composed of the p50 and p65 subunits. This induction appears specific since other transcription factors like AP-1 are only weakly activated by this treatment. In comparison with other inducing treatments such as phorbol esters or tumor necrosis factor alpha (TNF-alpha), the methylene-blue-mediated activation of NF-kappa B is slow, becoming optimal 180 min after treatment. These kinetic data were obtained by following, on the same samples, both the emergence of NF-kappa B in the nucleus and the disappearance of I kappa B-alpha in the cytoplasmic extracts. Conjugated with the induction of this transcription factor, HIV-1 reactivation from these latently infected cells was also observed by the measurement of reverse transcriptase activity in the cell supernatants. These data allow us to postulate that 1O2 is a biologically important reactive oxygen species which could play a role in the establishment of oxidative stress conditions leading to HIV-1 activation via the presence of NF-kappa B in the nucleus of infected cells.
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PMID:NF-kappa B transcription factor and human immunodeficiency virus type 1 (HIV-1) activation by methylene blue photosensitization. 770 61

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

ICR mice were infected intranasally with Mycoplasma pulmonis isolated freshly from the lungs of a rat with pneumonia. We demonstrated with high reproducibility the expressions of messenger RNAs of cytokines, tumor necrosis factor alpha (TNF alpha) and interferon gamma (IFN gamma) in the lung tissue of M. pulmonis-infected mice by the reverse transcriptase-polymerase chain reaction and confirmed specific mRNA of the cytokines by restriction endonuclease digestion. Both the viable population of M. pulmonis in the lung tissue and the titers of the neutralizing antibody in the serum increased between 7 and 21 days, and reached their maximum 35 days after infection. The pneumonia in mice progresses with the development of lung lesions after 7 days of infection. The early lesions are characterized primarily by neutrophils and edema in the alveolar spaces. mRNAs prepared from the lung tissue of M. pulmonis-infected and -uninfected mice were also tested for the presence of messages specific to TNF alpha and IFN gamma by the reverse transcriptase-polymerase chain reaction. The expression of the genes encoding TNF alpha and IFN gamma was constitutively demonstrated from 24 hr through 35 days after the intranasal inoculation of M. pulmonis. Furthermore, cells of two types, adherent and nonadherent cells, in bronchoalveolar lavage fluids obtained from the mice 3 weeks after inoculation of M. pulmonis were also found to express the genes of TNF alpha and IFN gamma respectively. These data suggest that these cytokines would play a role in both stimulation in the development of pathological changes in mycoplasmal infection, affecting the inflammatory responses.
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PMID:Gene expression of tumor necrosis factor alpha and interferon gamma in the lungs of Mycoplasma pulmonis-infected mice. 793 58

Rejection continues to be a major cause of graft loss in small intestine transplantation (SIT). We have studied, by semiquantitative reverse transcriptase PCR (rtPCR), the intragraft expression of cytokines relevant to rejection in a rat model. Heterotopic SIT grafts were performed from Lewis x Brown Norway F1 donors into Lewis recipients. The isograft control was Lewis into Lewis. Five animals in each isograft and allograft group were sacrificed on POD 3, 5, 7, 8, 9, 10, 12, and 14. mRNA was isolated from portions of the terminal ileum and rtPCR performed to amplify message for interleukin-2 (IL-2), IL-2 receptor (IL-2R), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), and interferon gamma (IFN-gamma). Semiquantitative analysis was performed using 32P radionuclide incorporation and scintillation counting. The results were expressed as percent activity compared with beta-actin. Histologic correlation with cytokine expression was made. On POD 3 after SIT there was no evidence of rejection by histology and all cytokines studied showed no difference between the isograft and the allograft. On POD 5 the first evidence of mild rejection was seen on histology and IL-6, IFN-gamma, TNF-alpha showed a significant up regulation in the allograft that persisted through POD 14. mRNA for IL-2 was not significantly upregulated until POD 7 and persisted until POD 14. IL-2R was constitutively expressed in both isograft and allograft and was not a reliable predictor of rejection. Histologic rejection was moderately severe by POD 7 and severe between POD 8 and 14 correlating with the increasing expression of IL-6, IFN-gamma, and TNF-alpha. In summary, we have shown that increasing expression of mRNA for IL-6, IFN-gamma, and TNF-alpha not only correlated with severity of rejection but that upregulation began early when histologic evidence of rejection first occurred.
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PMID:The correlation of intragraft cytokine expression with rejection in rat small intestine transplantation. 794 Jun 88

The nature of the host cellular immune response largely determines the expression of disease following infection with the intracellular protozoans Leishmania spp. In experimental animals control and resolution of infection are mediated by gamma interferon and tumor necrosis factor alpha (TNF-alpha), whereas disease progression is associated with the production of interleukin 4 (IL-4), IL-5, IL-10, and transforming growth factor beta (TGF-beta). We have analyzed the profile of cytokine gene expression directly in the lesions of 13 patients with localized cutaneous leishmaniasis due to Leishmania mexicana. All but one patient had a single lesion, and the time of evolution ranged from 8 days to 18 months. Cytokine gene expression was quantitated by reverse transcriptase PCR and interpolation from a standard curve. Gamma interferon, TNF-alpha, IL-1 alpha, IL-6, IL-10, and TGF-beta gene expression was present in all samples. IL-3 and IL-4 gene expression was barely detectable in 1 and 3 of 13 samples, respectively. IL-2 and IL-5 mRNAs were not found. A significant increase in the expression of IL-1 alpha, TNF-alpha, IL-10, and TGF-beta was observed in late lesions (> or = 4 months) compared with that in early lesions (< or = 2 months). Because of their inhibitory effects on macrophage function, the expression of IL-10 and TGF-beta may play a role in the immunopathogenesis of chronic cutaneous leishmaniasis.
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PMID:Increased expression of proinflammatory cytokines in chronic lesions of human cutaneous leishmaniasis. 811 53

In order to better understand the immunoregulation following Mycobacterium tuberculosis infection, cytokine mRNA induction in response to in vitro infection of human monocytes with live virulent M. tuberculosis H37Rv cocultured with autologous lymphocytes was quantitated by reverse transcriptase-PCR. Induced levels of interleukin 1 beta (IL-1 beta), IL-2, tumor necrosis factor alpha, and gamma interferon (IFN-gamma) were compared among groups of individuals representing three phases of immunity to infection with M. tuberculosis: naive normal control subjects, purified protein derivative (PPD)-reactive normal donors, and individuals with active tuberculosis (TB [diseased]). Levels of IL-1 beta and tumor necrosis factor alpha mRNA in cocultured cells from TB patients were 51 and 45%, respectively, of those obtained in cells from sensitized healthy volunteers and were comparable to those from naive normal donors. Lymphoproliferative responses to M. tuberculosis and induction of the T-cell cytokine IL-2 were predictably high in the cells of PPD-sensitized donors, low in normal naive individuals, and variable among TB patients. In contrast, the induced level of another lymphokine, IFN-gamma, did not follow the pattern seen in IL-2 induction. Infection with live M. tuberculosis induced high levels of IFN-gamma mRNA in lymphocytes of both PPD-sensitized and normal naive donors compared with those of TB patients. Interestingly, polyclonal stimulation with the mitogen concanavalin A induced similar IFN-gamma levels in cells from all three donor groups. The high level of IFN-gamma induced by the infection of monocytes from naive normal donors suggests a role for natural killer (NK) cells in the production of IFN-gamma in this coculture system. This response appears independent of the role performed by T cells.
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PMID:Cytokine gene expression by cultures of human lymphocytes with autologous Mycobacterium tuberculosis-infected monocytes. 813 51

In pulmonary sarcoidosis or experimental granuloma formation, interleukin-1 beta (IL-1 beta) or tumor necrosis factor alpha (TNF-alpha) are considered to play important roles during inflammatory evolution. In order to examine whether IL-1 beta or TNF-alpha mRNA expression on lung macrophages relates to the disease activity or clinical course, ten cases with pulmonary sarcoidosis were divided into two groups: five cases who had a disease duration of more than 10 years (14.6 +/- 4.4 years; group A), and 5 cases with duration of less than 3 years (1.7 +/- 1.1 years; group B). All cases showed both abnormal radiographs and elevated serum angiotensin converting enzyme activities. We compared the 10 cases with 12 healthy individuals as normal control (6 nonsmokers: NS and 6 current smokers: S), and 5 cases with idiopathic pulmonary fibrosis (IPF) as disease control. Lavage macrophages were purified by rosette forming method and plastic adhesion was then performed for 1 hour. Thereafter mRNA was extracted by AGPC method and amplified by reverse transcriptase-polymerase chain reaction (RT-PCR) (20 cycles). The results showed that IL-1 beta mRNA was detected in all materials studied, but TNF-alpha mRNA expression was different among the groups: 5/5 (100%) in group A, 1/5 (25%) in group B, 5/5 (100%) in IPF, and 12/12 (100%) in normal controls. The absence of detection of TNF-alpha mRNA (rapid down regulation) in pulmonary sarcoidosis may relate to spontaneous regression, because a substantial number of cases in group B showed spontaneous regression in their natural course.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Differential detection of IL-1 beta and TNF-alpha mRNA on lung macrophages from patients with pulmonary sarcoidosis]. 825 14

Bone marrow (BM) and peripheral blood (PB) cells from patients with juvenile chronic myelogenous leukemia (JCML) exhibit spontaneous in vitro proliferation. Several cytokines including granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-1 beta (IL-1 beta), and tumor necrosis factor alpha (TNF alpha) have been implicated in supporting the growth of leukemic monocyte-macrophage colonies either by autocrine or paracrine pathways. In seven untreated JCML patients, we investigated the role of IL-1 in the spontaneous growth of these cells by specifically blocking IL-1 receptors. The IL-1 receptor antagonist (IL-1 Ra) was added to the clonogenic assays, and in each case significant (mean = 63%, range = 35% to 82%) inhibition of spontaneous proliferation was observed. Uncultured circulating cells from PB or BM of four out of five patients expressed IL-1 beta-specific mRNA and secreted the protein into the culture supernatants. Moreover, by means of reverse transcriptase-polymerase chain reaction (RT-PCR), we demonstrated that most of the spontaneously growing leukemic colony-forming unit cells (CFU-C) obtained from BM cells of two patients were positive for the presence of the IL-1 beta-specific mRNA. Despite the presence of a measurable amount of GM-CSF in JCML cell culture supernatants, GM-CSF-specific mRNA in CFU-C cells of four cases was not detected by RT-PCR. These data further support a central role for IL-1 beta in the pathogenesis of JCML and suggest that the use of IL-1 Ra could represent a novel therapeutic strategy against this disorder.
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PMID:Suppression of juvenile chronic myelogenous leukemia colony growth by interleukin-1 receptor antagonist. 794 96

ICR mice were infected intranasally with Mycoplasma pulmonis isolated freshly from the lungs of the rats with pneumonia. We demonstrated with high reproducibility the expressions of messenger RNAs of cytokines, tumor necrosis factor alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the lung tissue of M. pulmonis-infected mice. Both the viable population of M. pulmonis in the lung tissue and the titers of the neutralizing antibody in the serum increased in 7 and 14 days, respectively, and reached their maxima in 35 days after infection. Macroscopical and microscopical lesions were evident in the lungs of the mice inoculated with M. pulmonis and sacrificed in 21 days after the inoculation. Microscopically, mild infiltration of mononuclear cells and neutrophils in peribronchial and perivascular spaces were observed. The alveolar septa were swollen with infiltration of these cells. Next, mRNAs prepared from the lung tissues of M. pulmonis-infected and -uninfected mice were tested for the presence of messages specific to TNF-alpha and IFN-gamma by the reverse transcriptase-polymerase chain reaction. The expression of the genes encoding TNF-alpha and IFN-gamma was constitutively demonstrated from 24h through 35 days after the intranasal inoculation of M. pulmonis. Furthermore, cells of two types, adherent and nonadherent cells, in bronchoalveolar lavage fluids obtained from the mice 3 weeks after inoculation of M. pulmonis were found also to express the genes of TNF-alpha and IFN-gamma. These data suggest that these cytokines would play a role in both stimulation and inhibition in the development of pathological changes in mycoplasmal infection, affecting the inflammatory responses.
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PMID:[Gene expression of tumor necrosis factor-alpha and interferon-gamma in the lungs of Mycoplasma pulmonis-infected mice]. 831 7


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