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)

Experimental animal models have shown that various cytokines, depending of their specific properties, may support growth and metastasis of tumor cells or even lead to tumor rejection. The analysis of expression of cytokine genes by melanoma cell lines indicated that melanoma cells constitutively produce both autostimulatory and inhibitory cytokines. Using reverse transcriptase polymerase chain reaction analysis, simultaneous expression of several cytokines, including interleukin-1 beta (IL-1 beta), IL-6, IL-8, tumor necrosis factor-alpha, and granulocyte-macrophage colony-stimulating factor, by melanoma cells was found. The same cytokine transcripts were detected in melanocytes, suggesting that cells of the melanocytic lineage express a specific pattern of cytokines in vitro. All these cytokines are known to be able to stimulate effector cells of the host. Additionally, production of mRNA for IL-10, a cytokine with potential immunosuppressive properties, was detected in melanoma cells and melanocytes. These and other cytokines are likely to be involved in the immune response to cancer and at this time it is unknown what the net effects of multiple cytokines are on the outcome of the host response to tumor.
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PMID:Production of cytokines by human melanoma cells and melanocytes. 759 87

Several lines of evidence indicate that an impairment of EBV-specific immune responses may contribute to the pathogenesis of Hodgkin's disease (HD). At present, however, it is not clear whether a defective immunity to EBV is a characteristic restricted to EBV-associated HD cases or a more generalized phenomenon, part of the inherent immune deficiency of HD patients. In this study, we have addressed this issue by analyzing EBV-specific responses in infiltrating T lymphocytes (TILs) from one HD biopsy, where the virus was confined to a small proportion of apparently normal lymphocytes. TIL cultures were established using low amounts of recombinant interleukin 2 and in the absence of specific stimulation, conditions that preferentially induce the proliferation of in vivo activated T cells. An EBV-specific cytotoxic component was revealed by the capacity of these TILs to lyse autologous EBV-positive lymphoblastoid cell lines (LCLs) obtained by spontaneous transformation from the lesion but not HLA-mismatched LCLs and autologous phytohemagglutinin blasts. This cytotoxic activity closely resembled that of EBV-specific memory T cells, which may be reactivated from the blood lymphocytes of healthy donors by in vitro stimulation with autologous LCLs. The use of a panel of appropriately HLA-matched B95.8-transformed LCLs as targets in standard 51Cr release assays revealed EBV-specific cytotoxic responses to be restricted mainly through the A11 and B44 HLA alleles with a minor HLA-A26-restricted component. Using autologous fibroblasts infected with recombinant vaccinia viruses expressing the EBV latent antigens, the TIL culture was shown to recognize latent membrane protein 2 and, to a lesser extent, EBV-encoded nuclear antigen 6. In addition, a strong proliferative response was induced by coculture of TILs with autologous but not with allogeneic LCLs or autologous phytohemagglutinin blasts. Six CD4-positive, EBV-specific T-cell clones were isolated by limiting dilution. The study of cytokine mRNA expression, carried out by reverse transcriptase-assisted PCR, revealed that three of these T-cell clones expressed a Th0 phenotype, whereas 1 had a Th2 phenotype. These findings are consistent with the presence in this HD lesion of an ongoing immune response against EBV-carrying cells and suggest that the complex immune deficiency that characterizes HD patients probably does not include a generalized, constitutional defect of EBV-specific T-cell responses.
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PMID:Identification and characterization of an Epstein-Barr virus-specific T-cell response in the pathologic tissue of a patient with Hodgkin's disease. 762 78

Experimental autoimmune uveoretinitis (EAU) was induced in Lewis rats and the inflamed retinas were examined for IFN-gamma, IL-2, IL-4, and IL-10 mRNA production at serial time points using the reverse transcriptase-polymerase chain reaction. IFN-gamma, IL-2, IL-4, and IL-10 mRNAs were all detected 24 hr before the earliest time point at which histological changes have previously been detected. IFN-gamma, IL-2, and IL-4 mRNA expression peaked during the active phase of the disease and declined in parallel with lymphocyte numbers as the inflammation resolved. IL-10 mRNA levels increased more slowly, reaching a maximum at later stages of disease. The observed pattern of cytokine mRNA expression in the retina in EAU is similar to that reported in experimental autoimmune encephalomyelitis (EAE). The increase in IL-10 mRNA expression in late disease may reflect a role in disease resolution as previously proposed in EAE.
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PMID:The kinetics of cytokine mRNA expression in the retina during experimental autoimmune uveoretinitis. 763 45

In addition to infiltrating inflammatory cells, tumors also produce cytokines and growth factors that may alter tumor growth, tumor immunogenicity, and the host immune response. To characterize the expression profile of human non-small cell lung cancer (NSCLC)-derived cytokines, the mRNA expression of type 1 and type 2 cytokines in five human NSCLC lines was analyzed by reverse transcriptase-PCR. Expression of interleukin 5 (IL-5) and IL-10 was demonstrated in all tumor lines evaluated, whereas IL-4 was present in three of five lines and IL-13 was present in two of five lines. In contrast, none of the tumor lines expressed IL-2 and IFN-gamma. Type 2 cytokine protein production by NSCLC lines was confirmed by immunoprecipitation and cytokine specific ELISA. Tumor-derived IL-10 secretion was significantly augmented by exogenous recombinant cytokines including IL-4 and tumor necrosis factor-alpha. To evaluate whether fresh NSCLC nodules also express a type 2 cytokine pattern, the content of type 1 and type 2 cytokines in tissue homogenates from 13 fresh NSCLC nodules and normal lung surgical specimens was assessed. Human NSCLC nodules contain significantly more type 2 cytokines than does normal lung tissue when corrected for total protein concentration. To identify the cellular source of type 2 cytokine production in tumor nodules, immunohistology was performed on sections from 5 lung squamous cell carcinomas and 5 adenocarcinomas. All of the specimens revealed positive staining for type 2 cytokines within tumor cells. In summary, we report that human NSCLC cells produce type 2 cytokines both in situ and in vitro, which may play an active immunoregulatory role in the lung cancer microenvironment.
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PMID:Human non-small cell lung cancer cells express a type 2 cytokine pattern. 764 Dec 3

Dysregulation in cytokines has been associated with melanomas. For example, loss of growth inhibition in advanced melanomas has been associated with interleukin-6 (IL-6) expression. Because IL-6 belongs to the hematopoietic cytokine family, which includes leukemia inhibitory factor (LIF) and interleukin-11 (IL-11), we examined the possibility of coordinate expression of LIF, IL-6, and IL-11 in three human melanoma cell lines derived from primary lesions (early) and in four lines derived from metastatic tumors (advanced). All lines examined produced at least low levels of LIF and IL-11 mRNA as measured by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR). By enzyme-linked immunosorbent assay (ELISA), two of three early and three of four advanced lines were found to secrete LIF protein. IL-11 was assayed using growth of the responsive B9/11 cell line, but only one of seven lines made a low but measurable amount of IL-11. Cytokine protein production was not strictly correlated with mRNA abundance, nor was it strongly correlated with tumor staging. Recombinant LIF and IL-11 protein had no effect on the proliferation of any of the seven lines, suggesting that they do not act as autocrine growth factors for these melanomas. Assay of IL-6, IL-11, and LIF protein in conditioned medium from early and advanced melanoma lines gave no evidence of coordinate expression of these cytokines. We conclude that LIF and IL-11 production by melanomas may have some paracrine or endocrine function in the course of melanoma progression.
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PMID:Expression of leukemia inhibitory factor and interleukin-11 by human melanoma cell lines: LIF, IL-6, and IL-11 are not coregulated. 764 48

We established an improved non-radioactive in situ hybridization (ISH) method to detect mRNA of cytokines in cell preparations and tissues. Via this method we could demonstrate various cytokines in stimulated peripheral blood mononuclear cells (PBMC), lymphoid cell lines and human lymphoid tissues. The probes for the in situ hybridization were made by labelling cytokine-specific PCR products with digoxigenin (Dig) in a repeated PCR. This resulted in an intrinsic labelling of the probe with several Dig-UTP molecules. Incorporation of Dig-11-dUTPs was shown on ethidium bromide-stained agarose gels by a higher molecular weight of the PCR products with incorporated Dig-dUTPs when compared to control PCR products without digoxigenin. Cytospin-centrifuged cells of PHA-stimulated PBMC or lymphoid cell lines and frozen sections of various human lymphoid tissues were hybridized with the Dig-labelled cytokine probes and the hybridized probes were detected immuno-histochemically. In this way, we detected and localized cytokine mRNAs (IL-2, IL-4, IL-6, IL-8, IL-10) in PBMC, in the human T-cell line Jurkat, in the follicular lymphoma cell line DoHH2, and in human lymph nodes and tonsils. The in situ hybridization had a high sensitivity as the results correlated closely with the detection of cytokine mRNA by reverse transcriptase-PCR (RT-PCR) data from the same samples. We showed that Jurkat and DoHH2 cells produce several cytokines constitutively and that, after activation with the phorbol ester PMA, expression of several cytokine mRNAS was enhanced.
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PMID:An improved, sensitive, non-radioactive in situ hybridization method for the detection of cytokine mRNAs. 765 59

Although many cytokines have been previously implicated in graft-versus-host disease (GVHD), no study to date has comprehensively evaluated their expression over time or in different tissues affected by GVHD. Using a semi-quantitative reverse transcriptase-PCR technique and a murine model of acute GVHD, we have evaluated the expression levels of mRNA for a wide range of cytokines in spleen, gut and liver tissues at weekly intervals after bone marrow transfer. The earliest cytokine responses seen were increases in IL-2, IL-10, IFN-gamma, MIP-1 alpha and TNF-alpha in the spleen, suggesting a primarily Th1 pathway. Other cytokines (IL-1 alpha, IL-10 and MIP-1 alpha) were persistently elevated in GVHD mice, but were variable depending on the tissue. These data demonstrate that a wide range of cytokines are involved in the GVHD response and that their kinetic pattern of expression is different in various affected tissues.
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PMID:Kinetic and organ-specific patterns of cytokine expression in acute graft-versus-host disease. 765 87

BALB/c and CBA/CaH mice show discrete, genetically determined patterns of tissue responses to infection with the yeast Candida albicans. By use of a semiquantitative reverse transcriptase-polymerase chain reaction, interferon (IFN)-gamma, interleukin (IL)-6, and tumor necrosis factor (TNF)-alpha were readily demonstrated in brain tissue on days 1, 3, and 5 after infection and were present in higher concentrations in CBA/CaH than in BALB/c mice. IL-2 and -4 were detected in both strains but at different time points. Both the fungus burden and the severity of the tissue damage become established before mRNA concentrations of the cytokines increase in the lesions, and the rate of clearance of the yeast is similar in both mouse strains. The data indicate that the deterministic model, which correlates Th1 and Th2 cytokines with resistance and susceptibility, respectively, is inadequate to account for the patterns of cytokine production that develop in the infected brain after sublethal challenge.
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PMID:Cytokine mRNA in brain tissue from mice that show strain-dependent differences in the severity of lesions induced by systemic infection with Candida albicans yeast. 765 77

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

A number of cytokines have been shown to have stimulatory activity on multipotent haematopoietic precursors. These include kit ligand (KL), interleukins (IL) 1, 3 and 6 and granulocyte macrophage-colony stimulating factor (GM-CSF). Using reverse transcriptase/polymerase chain reaction method (RT/PCR) we have examined the expression of these cytokines, the c-kit and IL-6 receptors, in long-term bone marrow culture (LTC) adherent layer cells in human bone marrow hypoplasia syndromes. Disorders studied include Fanconi's anaemia (FA, n = 16), idiopathic aplastic anaemia (AA, n = 11), Seckel's syndrome (n = 2), dyskeratosis congenita (n = 2), Shwachman-Diamond syndrome (n = 1), thrombocytopenia with absent radii syndrome (n = 1), acquired amegakaryocytosis (n = 1), paroxysmal nocturnal haemoglobinuria (n = 1) and acquired agranulocytosis (n = 1). IL-6 and GM-CSF expression appeared reduced in most patients with FA, suggesting that impaired production of these cytokines may contribute to the bone marrow failure seen in most patients with FA. In contrast, abundant IL-6 and GM-CSF expression were seen in most patients with AA when compared with the FA group and controls; these may be mediators of a stromal response in this disorder. No obvious differences were seen between the different patients' groups and controls in expression of the other cytokines or cytokine receptors studied.
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PMID:The expression of cytokine and cytokine receptor genes in long-term bone marrow culture in congenital and acquired bone marrow hypoplasias. 751 72


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