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)

ISG-15 is a 15-kDa protein encoded by an interferon (IFN)-stimulated gene (ISG), which is transcriptionally regulated by IFN-alpha and IFN-beta. Considered as part of the cytokine network, ISG-15 has the potential to amplify the immunomodulatory effects of these IFNs by enhancing IFN-gamma production, natural killer cell proliferation, and lymphokine-alphactivated killer cell cytotoxicity. To understand better the mechanism(s) of action of orally administered IFN-alpha, we have studied the effect of IFN-alpha on ISG-15 gene expression by human buccal epithelial cells (BEC). For in vitro studies, ISG-15 mRNA and protein levels were measured in BEC incubated for 0.5, 2, and 9 h with 100 or 1,000 IU/ml of human lymphoblastoid IFN-alpha. For in vivo studies, ISG-15 mRNA was measured in BEC samples collected at baseline, and 0.5, 2, and 9 h after 5-20 min of oral rinsing with 10 ml of IFN-alpha (1,000 IU/ml). ISG-15 mRNA was measured by reverse transcriptase polymerase chain reaction (RT-PCR), and ISG-15 protein production by Western Blot analysis. IFN-alpha augmented BEC ISG-15 gene expression in a concentration dependent manner both in vivo and in vitro. We conclude that orally administered IFN-alpha exerts its immunomodulatory effects in humans in part by upregulating the production of ISG-15 by BEC, thereby enhancing the immune reactivity of mucosa-associated lymphocytes.
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PMID:Oral use of interferon-alpha stimulates ISG-15 transcription and production by human buccal epithelial cells. 1047 39

The aim of the present study was to verify the expression of tumour necrosis factor (TNF)-alpha mRNA by semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) in unstimulated peripheral blood mononuclear cells (MNCs) of 15 relapsing-remitting multiple sclerosis (MS) patients who underwent treatment with IFN-beta 1a (6 millions of international units (MIU) i.m. once a week) and in 15 untreated MS patients matched for age and expanded disability status score (EDSS). At the same time the expression of TNF-alpha mRNA was assessed in 10 healthy age-matched control subjects. All MS patients were assessed at the basal time and after 6 months. At the basal time, the band of TNF-alpha mRNA was detectable in 12 out of the 15 untreated patients and in 13 out of the 15 patients who underwent IFN-beta 1a treatment. The higher TNF-alpha mRNA was evident in patients with gadolinium-enhancing lesions. At the 6-month follow-up, 13 out of the 15 untreated patients still had detectable values of TNF-alpha mRNA and no significant difference emerged when compared with basal time. On the contrary, the expression of TNF-alpha mRNA was absent at the same time in nine out of the 15 patients treated with IFN-beta 1a. A longitudinal analysis carried out monthly in eight MS patients (four untreated and four treated) revealed a transient increase in TNF-alpha mRNA expression in MNCs of all four treated patients in the first 3 months, supporting previous findings of an early immunoenhancing effect of IFN-beta 1a. This early activation is followed by an inhibitory effect of IFN-beta 1a on TNF-alpha mRNA expression in about 2/3 of treated MS patients when assessed at 6 months. Further long-term studies are needed to confirm this immunomodulatory effect of IFN-beta 1a not only on TNF-alpha but also on other cytokines of Th(1)and Th(2)types.
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PMID:Expression of TNF-alpha mRNA by peripheral blood mononuclear cells of multiple sclerosis patients treated with IFN-beta 1A. 1144 10

We examined the expression of mRNAs for inflammatory cytokines and Fas in cultured human fetal membrane cells responding to influenza virus (IV) infection using the reverse transcriptase-polymerase chain reaction (RT-PCR). Primary cultured chorion and amnion cells prepared from human fetal membranes were infected with IV. Chorion cells expressed significant amounts of interleukin (IL)-1beta, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-beta, IFN-gamma and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNAs and small amounts of Fas mRNA in response to IV infection. Amnion cells expressed TNF-alpha and IFN-beta mRNAs in response to IV infection, while expression of the other mRNAs was not altered. We also examined whether or not TNF-alpha, IFN-beta, IFN-gamma and Fas participated in IV infection-induced apoptotic DNA fragmentation in chorion cells. Neutralizing antibodies against them did not inhibit DNA fragmentation. These results suggested that chorion cells expressed significant amounts of mRNAs for inflammatory cytokines in response to IV infection, and that, in contrast, mRNA expression was quiescent in amnion cells. Moreover, TNF-alpha, IFN-beta, IFN-gamma and Fas do not appear to be directly involved in the apoptosis induction of IV-infected chorion cells. The results indicated that chorion cells may play a role in defense against IV through an antiviral immune response and apoptosis to eliminate own cells and viral pathogens in infected organs, whereas amnion cells do not play such a role.
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PMID:Differential mRNA expression of inflammatory cytokines in cultured human fetal membrane cells responding to influenza virus infection. 1185 74

Foot-and-mouth disease virus (FMDV) can cause transplacental infection and death in fetal lambs. This study investigates the pathogenesis of FMDV infection in ovine fetuses using in-situ hybridization (ISH) to detect viral transcripts in tissue and real-time reverse transcriptase polymerase chain reaction (RT-PCR) assays to quantify the fetal cytokine response to infection. FMDV ribonucleic acid (RNA) was localized mainly to the heart and skeletal muscles of fetuses and was only occasionally expressed in the lingual epithelium, demonstrating that FMDV has a different tissue tropism in the fetus compared with that in adult sheep. There was early expression of genes encoding anti-viral cytokines (IFN-alpha and IFN-beta) in fetuses at 2 and 4 days post-infection (dpi), followed by a marked rise in the transcription of pro-inflammatory cytokine genes (IFN-gamma, TNF-alpha and IL-1alpha) from 7 to 18 dpi, particularly in the heart. The degree of cytokine mRNA expression correlated with fetal infection and was likely to be a factor in fetal death. In contrast, cytokine gene expression in infected neonatal lambs was much less and mainly occurred between 2 and 4 dpi. This study identifies two key factors in the pathogenicity of FMDV in fetal lambs: viral tropism for cardiac and skeletal muscles, and a marked cytokine response following infection.
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PMID:Foot-and-mouth disease virus infection in fetal lambs: tissue tropism and cytokine response. 1829 84


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