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)

Although there have been reports regarding the clinical effectiveness of IFN alpha in the treatment of myeloma patients during this decade, its biological effects on human myeloma cells have still not been clarified. Recently, apoptosis has been considered as one of the most important mechanisms in the programmed cell death of malignant tumour cells induced by chemotherapeutic agents or cytotoxic immunological defence in malignancy-carrying hosts. Among the several pathways which function to induce apoptosis, Fas and the Fas ligand system have been thought to play an important role in inducing tumour-cell apoptosis, particularly in immunological prevention. In this study we investigated myeloma cell apoptosis induced by IFN alpha using five human myeloma cell lines which were established without any additional supplementation of IL-6. In addition, the mRNA expression levels of apoptosis-related genes employing the reverse transcriptase-polymerase chain reaction (RT-PCR) were also analysed with the KMS-12-PE cell line, which was the most sensitive of the five cell lines in terms of apoptosis induced by IFN alpha. Based on the results, it was determined that IFN alpha induced myeloma cell apoptosis in a dose-dependent manner, but the sensitivity to IFN alpha in the cell lines examined varied and one cell line revealed growth stimulation by IFN alpha. In addition, the apoptosis induced by IFN alpha did not seem to be mediated by the Fas/Fas ligand pathway. Finally, the IL-6, IL-6R, IRF1 and IRF2 genes were up-regulated in KMS-12-PE cells cultured with IFN alpha. Therefore these genes may play an important role during apoptosis induced by IFN alpha.
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PMID:Human myeloma cell apoptosis induced by interferon-alpha. 982 28

Interferon-gamma (IFN-gamma) produced by lesional T cell clones is critical for the induction into G1 of the cell cycle by psoriatic keratinocyte stem cells; however, direct data demonstrating psoriatic lesional T cell subset IFN-gamma expression, and quantitation at a single cell level to calculate in vivo proportions, are lacking. In this study, using flow cytometry of freshly isolated normal and psoriatic lesional T cells from keratome biopsies, we found elevated CD3+, CD4+, and CD8+ T cells in all compartments of psoriatic skin, compared with normals. Using Brefeldin A to induce short-term intracellular accumulation of IFN-gamma in T cells capable of IFN-gamma production, we found that 90% of psoriatic patients have IFN-gamma-producing T cells at a greater proportion of their CD3+ cells than normals, with a mean of 16%+/-3%, as compared with 4%+/-2% in normal epidermis (p = 0.01). Expressed as density in the tissue, the IFN-gamma+ CD3+ cell number in psoriatic epidermis was 97+/-22 per mm2 surface area, as compared with 4.4+/-1.8 per mm2 of normal epidermis (p = 0.002). Thus, the total number of IFN-gamma+CD3+ T cells in the skin of a patient with 20% involvement is estimated to be 3.9 x 10(8). CD4+ and CD8+ IFN-gamma+ T cells were both elevated in psoriatic epidermis (p = 0.04 and p = 0.008, respectively) relative to normal skin. In the dermis, only 44% of patients demonstrated a higher percentage of IFN-gamma-producing T cells than did normals (p = 0.1), possibly indicating dilution, in some patients, by fresh infiltrating T cells. Interleukin-4 was not found by a combination of flow cytometry, reverse transcriptase-polymerase chain reaction, western blot, and immunoprecipitation. In conclusion, a significant portion of lesional T cells in psoriasis are IFN-gamma producing, without interleukin-4. The increased numbers of both IFN-gamma+CD4+ and IFN-gamma+CD8+ T cells indicate that both CD4+ and CD8+ IFN-gamma+ T cells are present in appropriate anatomic locations to sustain the lesional pathology.
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PMID:Identification and quantitation of interferon-gamma producing T cells in psoriatic lesions: localization to both CD4+ and CD8+ subsets. 985 19

Various cytokines are upregulated in acute allograft rejection (AR). Local production of Th-1 cytokines is suggested to play a pathogenic role in AR, and Th-2 cytokines in the development of allograft tolerance. The purpose of this study was to correlate the expression of Th-1 [interleukin-2 (IL-2) and gamma-interferon (gamma-IFN)], and Th-2 [interleukin-10 (IL-10)] cytokines in bronchoalveolar lavage (BAL) fluid with AR in lung transplant (LT) recipients. The role of Th-1 dominance expressed as IgG2/IgG1 ratio in BAL in AR was also examined. The mRNA expression for IL-2, gamma-IFN and IL-10 was examined in 64 BAL specimens from 23 LT recipients using reverse transcriptase-polymerase chain reaction (RT-PCR). IgG1 and IgG2 levels were measured in 55 BAL specimens by enzyme-linked immunosorbent assay (ELISA). The expression on mRNA for these cytokines, and the ratio of IgG2/IgG1 was correlated with AR (early AR occurring within 3 months of transplant and late AR occurring after 3 months). Ten patients had 17 episodes of biopsy proven AR. Twelve episodes of AR (6 patients) occurred within the first 3 months of transplantation. In 5 patients, AR was diagnosed 4, 5, 6, 9 and 24 months post-transplantation. Detection of gamma-IFN mRNA correlated significantly with early AR (p < 0.001), whereas it lacked correlation with late AR. Expression of IL-2 and IL-10 mRNA did not correlate with AR. IL-10 was present in most samples irrespective of the presence or absence of AR. The ratio of IgG2/IgG1 was similar in patients with or without AR. Our findings suggest that the detection of gamma-IFN mRNA in BAL by RT-PCR is useful for immune monitoring of early AR in LT recipients. Absence of elevated IgG2/IgG1 ratio, and presence of IL-10 in BAL during AR suggests that Th-1 cytokines may not be the sole mediator of rejection in LT recipients.
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PMID:Expression of gamma-IFN mRNA in bronchoalveolar lavage fluid correlates with early acute allograft rejection in lung transplant recipients. 1020 18

Interferon-alpha (IFN-alpha) has shown promise in the treatment of chronic phase of chronic myelogenous leukaemia (CML). IFN-alpha has also been found to indirectly up-regulate the expression of major histocompatibility (MHC) antigens, and to directly increase the activity of lymphocytes against tumour cells. To elucidate whether IFN-alpha induces anti-leukaemic activity of the autologous T cells in CML patients, we analysed the accumulation of T-cell receptor (TCR) in each Vbeta family using the reverse transcriptase-polymerase chain reaction (RT-PCR) followed by single-strand conformation (SSCP) analysis. We found the predominant expression of the Vbeta 10, 12, and 14 families in the peripheral blood (PB) of CML patients, in contrast to healthy donors. Especially, in IFN-alpha-responsive patients, we observed an enhancement of the accumulation of the Vbeta 9 and 20 families, suggesting that T cells enhanced by IFN-alpha may react with a discrete set of antigens on the surface of malignant cells. These findings may demonstrate that CML cells possess the heterogenous antigens and the clonal expansion of Vbeta 9+ and Vbeta 20+ T cells may be a prognostic indicator of the immune responsiveness to IFN-alpha.
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PMID:Characterization of T-cell receptor beta chain mRNA expression in IFN-alpha-responsive chronic myelogenous leukaemia patients. 1023 81

Evidence is presented that the previously cloned type I duck interferon (DuIFN) cDNA encodes a homologue of mammalian interferon-alpha (IFN-alpha). Recombinant DuIFN-alpha was used to study the inhibition of duck hepatitis B virus (DHBV) replication in primary hepatocytes in order to determine the IFN-sensitive steps of the virus replication cycle. IFN-treated cells accumulated two- to threefold-lower amounts of viral RNA transcripts early during infection, when IFN was added before virus. This reduction was not due to inhibition of virus entry since initial covalently closed circular DNA levels were not decreased in IFN-treated cells. Interestingly, the inhibitory effect of IFN on viral RNA levels was not observed in cells infected with a mutant DHBV that fails to synthesize core protein, suggesting that an uncharacterized core protein-mediated enhancing effect is blocked by IFN. When IFN was added at 4 days postinfection, encapsidated viral RNA pregenomes disappeared from infected cells within 3 days. This depletion was not simply due to conversion of pregenomes to DNA since depletion was not blocked by phosphonoformic acid, an inhibitor of the viral reverse transcriptase. The intracellular concentration of intact nucleocapsids was reduced, suggesting that in the presence of IFN pregenome-containing capsids were selectively depleted in hepatocytes. Thus, two steps in DHBV replication that involve the viral core protein were inhibited by DuIFN-alpha.
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PMID:Elimination of duck hepatitis B virus RNA-containing capsids in duck interferon-alpha-treated hepatocytes. 1036 93

HIV-host infection systems in vitro are important in the pre-clinical assessment of anti-retroviral drug activity. The present report describes the development of a new HIV-host model comprised of an epithelial cell line of HeLa lineage (HeLa-1), transfected with expression vectors bearing tat and rev (TART) genes of HIV-1 as well as the CD4 receptor gene, and HIV-1(delta Tat/Rev), a biologically contained strain of HIV-1 deleted in tat and rev. Measurement of infectivity, by syncytium formation and reverse transcriptase assay, revealed that HeLa-1 is infected with HIV-1(deltaTat/Rev). This virus failed to productively infect the TART-deficient CD4-positive HeLa cells, confirming its contained, non-infectious nature. The HeLa-1/HIV-1deltaTat/Rev system was used to measure the anti-retroviral activity of a human leukocyte-derived interferon (IFN-alphan3) preparation, several nucleoside analogs, and protease inhibitors. The HeLa-1/ HIV-1(deltaTat/Rev model provides a biologically contained system for the study of the HIV pathogenesis and the relative and combined therapeutic effects of anti-retroviral agents in vitro.
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PMID:A new contained human immunodeficiency virus type 1 host cell system for evaluation of antiviral activities of interferons and other agents in vitro. 1044 30

Aquaporins are a family of homologous membrane proteins that function as highly selective water channels. Aquaporin-5 (AQP5) is uniquely present in lacrimal and salivary glands, where it accounts for normal tear and saliva production. We tested the hypothesis that orally administered human interferon-alpha (HuIFN-alpha) benefits persons with xerostomia by augmenting the production of AQP5 protein by parotid gland epithelium. Cells from three human parotid glands were cultured with and without human lymphoblastoid IFN-alpha, and assayed for AQP5 mRNA levels by reverse transcriptase polymerase chain reaction (RT-PCR), and AQP5 protein levels by Western blot. Intracellular localization of AQP5 protein was done using confocal microscopy. The functional integrity of the glandular tissue was confirmed by RT-PCR analysis of alpha-amylase 1 and basic proline-rich protein transcripts. AQP5 was constitutively expressed in human parotid gland tissue, with AQP5 protein restricted to the plasma membranes and cytoplasmic vesicles of acinar cells. IFN-alpha augmented AQP5 transcription and protein production in a concentration-dependent manner, and increased the size of intensity of staining of AQP5-containing cytoplasmic vesicles in acinar cells. We conclude that IFN-alpha upregulates AQP5 gene expression in human parotid acinar cells in vitro. To our knowledge, this is the first demonstration that IFN-alpha regulates the gene expression of an aquaporin.
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PMID:Interferon-alpha upregulates gene expression of aquaporin-5 in human parotid glands. 1047 40

Current strategies against the human immunodeficiency virus type 1 (HIV-1), including nucleoside analogues and protease inhibitors, have limited effectiveness as shown by the evolution of resistant retroviral strains and the presence of latent HIV-1 reservoirs. Therefore, it is necessary to look beyond anti-retroviral strategies and to rely on the body's immune system to inhibit HIV-1 replication. In this study, we approach the inhibition of HIV-1 replication by upregulation of the antiviral pathway that is natural to mammalian cells. Vectors were constructed which were capable of transferring the antiviral enzyme, p68 kinase (PKR), into target SupT1 lymphoblastoid cells under HIV-1 LTR transcriptional regulation via a retroviral-mediated shuttle system. We report a significant inhibition of HIV-1 replication in HIV-1 LTR-PKR cDNA transduced clones (105-10 : 239 and 106-4 : 560) expressing different PKR levels as measured by inhibition of HIV-1 induced syncytia formation and HIV-1 reverse transcriptase activity. Whereas the expression of PKR in parental vector transduced clone (N2-20P) is down-regulated 48 h after HIV-1 infection, the two transduced clones (one with PKR in the forward orientation and one in the reverse orientation) demonstrate increased PKR expression through 96 h post-infection, concomitant with an increase in eIF-2alpha phosphorylation and an increase in NF-kappaB activity at 72 h postinfection. These results demonstrate that the overexpression of PKR can inhibit HIV-1 replication and confirm the involvement of PKR in the IFN-associated antiviral pathway against HIV-1 infection. Finally, the treatment of the transduced clone 106-4 : 560 with AZT resulted in complete inhibition of HIV-1 replication.
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PMID:Inhibition of human immunodeficiency virus (HIV-1) replication in SupT1 cells transduced with an HIV-1 LTR-driven PKR cDNA construct. 1049 Nov 27

The BCR/ABL hybrid gene plays a central role in the pathogenesis of the chronic phase of chronic myeloid leukemia (CML). We used a very sensitive quantitative reverse transcriptase-polymerase chain reaction to investigate the levels of hybrid BCR/ABL mRNA in bone marrow cells of 20 patients with Philadelphia positive (Ph(+)) CML treated with interferon-alpha (IFN-alpha) as a single agent. Bone marrow samples were collected at diagnosis and at hematologic remission induced by IFN-alpha, or by hydroxyurea in case of resistance to IFN-alpha. The mean levels of BCR/ABL transcripts in bone marrow mononuclear cells of patients who showed a complete hematologic response to IFN-alpha were significantly reduced with respect to those at diagnosis (48 x 10(3) v 168 x 10(3); P <.001), whereas no difference was detected between the values at diagnosis and at hematologic remission in patients resistant to IFN-alpha. In cell culture experiments, IFN-alpha priming significantly reduced the levels of BCR/ABL hybrid transcripts in a dose-dependent manner in Ph+ bone marrow precursors obtained at diagnosis from patients who subsequently responded to IFN-alpha treatment (P < .005). No downmodulation was observed in bone marrow precursors from patients who subsequently proved to be IFN-resistant. These results indicate that downmodulation of BCR/ABL gene expression could be one of the mechanisms involved in the response of CML patients to IFN-alpha treatment.
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PMID:BCR/ABL mRNA and the P210(BCR/ABL) protein are downmodulated by interferon-alpha in chronic myeloid leukemia patients. 1049 89

Feline immunodeficiency virus (FIV) was first isolated in 1987 from a cat with an acquired immunodeficiency syndrome (AIDS)-like disease. Since then, FIV has been subject of intensive research. Perturbation in cytokine production observed in human immunodeficiency virus infection (HIV) is paralleled in the FIV-infected cat. Interferon gamma (IFN-gamma) is a type 1 lymphokine that exert protective effects during infection through upregulation of cellular immunity and phagocytic functions. The present study was carried out to examine the expression of IFN-gamma in a feline T-lymphoid cell line (Fel-039) infected with FIV as well as the viral replication in these cells after addition of recombinant-type feline IFN (rIFn). We found a marked inhibition of IFN-gamma release in Fel-039 cells infected with FIV which might be pivotal for high viral replication. Infection of Fel-039 cells with FIV resulted in an increase of the reverse transcriptase (RT) activity in the culture supernatant. When the cells were cultured in the presence of rIFN a significant dose-dependent inhibition of RT activity of FIV was detected without cytotoxicity. On the basis of these in vitro results, we suggest that IFN therapies aimed at restoring depleted level of this important cytokine in FIV infected T-cells make this compound a promising candidate for development of suitable drugs for AIDS treatment.
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PMID:[Feline immunodeficiency virus infection: interferon gamma secretion in a T-lymphoblastoid infected cell line]. 1050 91


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