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)

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.
Cytokine 1995 Apr
PMID:Cloning, sequencing and expression of the ovine interleukin 6 gene. 764 Mar 42

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.
J Interferon Cytokine Res 1995 May
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

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

Expression of the IL-13 gene in malignant tissues from 26 human B-cell lymphoid malignancies was analyzed by reverse transcriptase-polymerase chain reaction (RT-PCR). A positive signal was detected in 16 cases, which included high grade B lymphomas, follicular lymphomas and B-cell chronic lymphocytic leukemias. IL-13 mRNA was also detected in the 9 malignant B cell lines and in the 6 lymphoblastoid cell lines tested, as well as in freshly isolated malignant B cells from 2 patients with a Burkitt's lymphoma. Two of 8 T-cell lymphomas and 2 of 4 T-cell lines expressed the IL-13 gene. In contrast, IL-13 gene expression was not detected in any of the 5 non-lymphoid cell lines tested. No specific binding of radiolabeled IL-13 was detected on B cell lines, suggesting an absence of IL-13 receptors on such cells. This conclusion was also supported by the inability of IL-13 or anti-IL-13 antibodies to affect the growth of malignant B cells. Taken together, these results show that both malignant and EBV-transformed B lymphocytes, either freshly isolated or maintained as cell lines, express the IL-13 gene. This raises the question of the role of B lymphocyte-derived IL-13, a B lymphocyte stimulating cytokine, on the in vivo function of normal B lymphocytes as well as on the in vivo behaviour of B lymphoid malignancies.
Eur Cytokine Netw
PMID:Interleukin-13 gene expression by malignant and EBV-transformed human B lymphocytes. 772 91

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.
Cytokine 1995 Feb
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

Transforming growth factor-beta (TGF-beta) and interleukin-1 (IL-1) are essential participants in the development of pulmonary fibrosis. Administration of inhibitors to either cytokine can prevent the onset and progression of lung fibrosis in animal models. In this report, stable Thy-1+ and Thy-1- murine lung fibroblast subpopulations were analyzed for expression of the three mammalian TGF-beta isoforms. TGF-beta 1, TGF-beta 2, and TGF-beta 3 mRNA transcripts were detected by reverse transcriptase-PCR in both murine fibroblast subsets. Most of the TGF-beta produced by fibroblasts is latent; however, a small amount of active TGF-beta can be detected using a sensitive mink lung cell bioassay. By incorporating neutralizing anti-TGF-beta isoform-specific antibodies, it was determined that TGF-beta 1 is the predominant isoform present in both the active and the latent forms. Overall, Thy-1- fibroblasts secrete twice as much latent TGF-beta as the Thy-1+ subset. To investigate whether a link exists between TGF-beta and IL-1, the effect of TGF-beta 1 on the expression of IL-1 receptor type I (IL-1RtI) by fibroblast subsets was assessed by flow cytometry and Scatchard analysis. TGF-beta 1 significantly down-regulates the expression of IL-1RtI by Thy-1+ fibroblasts, but not by Thy-1- fibroblasts. A functional consequence of this down-regulation of the IL-1RtI is that it makes Thy-1+ fibroblasts less responsive to IL-1-mediated induction of IL-6 protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Lymphokine Cytokine Res 1994 Oct
PMID:Expression of TGF-beta isoforms by Thy-1+ and Thy-1- pulmonary fibroblast subsets: evidence for TGF-beta as a regulator of IL-1-dependent stimulation of IL-6. 785 60

The dermal papilla is a discrete group of cells at the base of the hair follicle and is implicated in controlling the hair growth cycle. Early passage dermal papilla cells can induce hair growth in vivo, but, upon further culturing, this property is lost. In order to study the events occurring in hair induction, a representative dermal papilla cell line was required. We have transfected passage 1 rat vibrissa dermal papilla cells with a polyomavirus large T gene encoding a temperature-sensitive T antigen, and generated permanent cell lines in which the immortalizing function can be switched off by temperature shift. The cells established without crisis, resembled cells in the starting population, and retained the aggregative properties of early passage dermal papilla cells. Growth studies were performed on the immortalized cell lines, which showed that transferring the cells to the restrictive temperature for the large T gene product resulted in cell senescence or quiescence, and changes in morphology. Implantation of cell pellets into the ears of immunologically compatible rats showed that the immortal cells retained hair-inductive ability. Cytokines are believed to have an important role in the control of hair growth. The pattern of cytokine gene expression in the immortal cell lines was compared with early passage dermal papilla cells and a non-hair-inducing dermal papilla cell line, using reverse transcriptase-polymerase chain reaction. Epidermal growth factor, tumour necrosis factor, and interleukin-1a were detected in the immortalized and non-hair-inducing dermal papilla cell lines, but were absent in passage 2 dermal papilla cells. All other cytokines examined were detected in all the cell types under study. These results demonstrate that the polyomavirus large Ttsa-immortalized dermal papilla cell lines are very similar to passage 2 dermal papilla cells and thus provide a good model for hair growth studies. Cytokine expression profiles indicate that the expression of several cytokines may be implicated in hair induction. Further studies are under way to investigate the relationship between cytokine expression and the hair growth cycle.
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PMID:Transfection of rat dermal papilla cells with a gene encoding a temperature-sensitive polyomavirus large T antigen generates cell lines retaining a differentiated phenotype. 798 46

The myocardial ischemia and reperfusion injury is caused by the re-introduction of coronary circulation in ischemic myocardial tissues. A number of experiments demonstrate that immunological response such as adherence of neutrophils to endothelial cells play a critical role in reperfusion injury. In this paper, the effect of global ischemia and reperfusion on the expression of cytokine genes by myocardial tissues as well as cell adhesion molecules by neutrophils were studied by using Langendorff model. Cardiac dysfunction and immunological response in 25 min global ischemia at 37.5 degrees C followed by 60 min reperfusion were studied in isolated rat heart perfused with blood supplied from support rat (Langendorff model). Cardiac functions were measured with a left intraventricular balloon. The mean post-experimental reduction of the left ventricular end-systolic pressure were 87.5 +/- 1.6% of pre-experimental level in the control perfusion group and 55.5 +/- 5.8% in the reperfusion group. Immunofluorescence flow cytometry showed that ischemia and reperfusion injury did not affect the expression of adhesion molecules on neutrophils which were isolated from perfused blood samples. Cytokine gene expression was analyzed by direct analysis of mRNA obtained from the blood-perfused, isolated rat heart. The level of expression of the cytokine genes was assessed using semiquantitative reverse transcriptase-polymerase chain reaction (semiquantitative RT-PCR). IL-6, IL-8, IFN-gamma, TNF-alpha were expressed in normal heart tissue at low level and were upregulated following ischemia and reperfusion. IL-1 beta, MCP-1 and IL-1 receptor antagonist were not expressed at detectable level in normal heart but were induced following global ischemia. IL-1 alpha was not expressed at detectable level in normal heart but was induced following reperfusion of the ischemic heart. Histological examination of myocardial tissue from the reperfusion group revealed no evidence of myocardial necrosis. Only a mild interstitial edema as well as weak focal hemorrhage was detected after reperfusion of ischemic hearts. These results suggest that there is a process which causes early stage of post-ischemic myocardial dysfunction without involving myocardial necrosis nor infiltration of inflammatory cells.
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PMID:[Cardiac dysfunction and endogenous cytokines in global ischemia and reperfusion injury]. 811 7

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

Interleukin-10 (IL-10) production by B lymphocytes has previously been demonstrated for malignant cells and for in vitro activated normal B cells. Spontaneous in vivo production of IL-10 by normal B lymphocytes has only been demonstrated in mice, in which autoreactive Ly 1 + B cells are involved. In the present study, spontaneous expression of the IL-10 gene by peripheral blood mononuclear cells was investigated in systemic lupus erythematosus (SLE), a human disease involving autoreactive B cells. Of the 47 SLE patients tested by coupled reverse transcriptase-polymerase chain reaction, 34 scored positive, contrasting with only 1 positive out of 34 normal subjects (p < 0.001). Spontaneous in vitro production of IL-10 by PBMC, determined using an ELISA assay, was 33 times higher in SLE than in controls (2623 +/- 728 pg/ml vs 79.3 +/- 34.5 pg/ml, respectively) (p < 0.001). The level of production of IL-10 in SLE was unrelated to either clinical or biological markers of disease activity. Among PBMC, monocytes and B lymphocytes both contributed to IL-10 production, whereas T cells did not. IL-10 overproduction in SLE suggests that this Th2-type interleukin plays a role in the production of autoantibodies through pathways involving both paracrine production by monocytes and autocrine IL-10 production by autoreactive B cells.
Eur Cytokine Netw
PMID:Spontaneous production of interleukin-10 by B lymphocytes and monocytes in systemic lupus erythematosus. 818 74


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