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)

Increased levels of chemokines (CK) in chronic hepatitis C virus (HCV) infection have been found. Given that NS5A and core can function as transcriptional transactivators, we aimed to determine whether these HCV proteins might induce CK gene expression in human hepatocyte-derived cells. We assessed (i) regulated upon activation, normal T cells expressed and activated (RANTES), interferon gamma-inducible protein-10 (IP-10), and monokine induced by interferon-gamma (MIG) mRNA levels in NS5A and core stably transfected Chang liver (CHL) cells, stimulated or not with a cytokine mixture (CM), by reverse transcriptase-polymerase chain reaction (RT-PCR) and (ii) quantitative enzyme-linked immunosorbent assay (ELISA) measurements of these CK in the supernatants of CHL cells. Induction of RANTES transcripts in resting HCV-transfected cells was clearly observed, being augmented fourfold in resting NS5A-transfected cells and threefold in resting core-transfected cells over that in resting mock-transfected (control) cells, as well as to a similar extent in CM-stimulated NS5A- and core-transfected cells. Increased RANTES secretion followed the same pattern observed for mRNA expression. Both IP-10 and MIG, such as mRNA and protein levels, were undetectable in resting HCV-transfected and -untransfected cells, whereas IP-10 and MIG mRNA expression was increased by seven- and fivefold in CM-stimulated NS5A-transfected cells and by 10- and 3.5-fold in CM-stimulated core-transfected cells, respectively, above that in CM-stimulated control cells. IP-10 and MIG secretion was enhanced by 2.6- and threefold in CM-stimulated NS5A-transfected cells and by 3.6-fold and 3.7-fold in CM-stimulated core-transfected cells, respectively over that in CM-stimulated control cells. These results demonstrate that NS5A and core proteins, alone or by the synergistic effect of cytokines, are capable of upregulating RANTES, IP-10 and MIG gene expression in cultured human hepatocyte-derived cells.
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PMID:Gene expression profile of T-cell-specific chemokines in human hepatocyte-derived cells: evidence for a synergistic inducer effect of cytokines and hepatitis C virus proteins. 1565 45

The majority of transplants are derived from donors who suffered from brain injury. There is evidence that brain death causes inflammatory changes in the donor. To define the impact of brain death, we evaluated the gene expression of cytokines in human brain dead and ideal living donors and compared these data to organ function following transplantation. Hepatic tissues from brain dead (n = 32) and living donors (n = 26) were collected at the time of donor laparotomy. Additional biopsies were performed before organ preservation, at the time of transplantation and one hour after reperfusion. Cytokines were assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and cytometric bead array. Additionally, immunohistological analysis of tissue specimens was performed. Inflammatory cytokines including IL-6, IL-10, TNF-alpha, TGF-beta and MIP-1alpha were significantly higher in brain dead donors immediately after laparotomy compared to living donors. Cellular infiltrates significantly increased in parallel to the soluble cytokines IL-6 and IL-10. Enhanced immune activation in brain dead donors was reflected by a deteriorated I/R injury proven by elevated alanin-amino-transferase (ALT), aspartat-amino-transferase (AST) and bilirubin levels, increased rates of acute rejection and primary nonfunction. Based on our clinical data, we demonstrate that brain death and the events that precede it are associated with a significant upregulation of inflammatory cytokines and lead to a worse ischemia/reperfusion injury after transplantation.
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PMID:Brain death activates donor organs and is associated with a worse I/R injury after liver transplantation. 1743 Mar 97

Non-protease inhibitor-based antiretroviral therapy (ART) is widely accepted as first-line ART in developing countries. Although reverse transcriptase inhibitor-based regimens have been studied in the peripheral blood, no studies have analyzed alterations in cytokine and chemokine levels, together in peripheral blood and genital secretions. Forty HIV-infected women with CD4 cell counts <200 cells/mm(3), asymptomatic, with no genital tract infection, willing to participate in the study, and adhere to ART were enrolled. Cervicovaginal lavage (CVL) was collected in the mid-cycle phase of menstrual cycle. Patients were initiated with reverse transcriptase-based antiretrovirals. Repeat sampling was performed at 24 weeks. Cytokines and chemokines were measured using ultrasensitive ELISA kits. Viral load declined to undetectable levels in 29 patients in the blood and in 33 cases in the CVL. Proinflammatory cytokines (tumor necrosis factor-alpha [TNF-alpha, interleukin-6 [IL-6], IL-1beta) in the serum and CVL showed a significant decrease in mean levels after therapy. IL-2 levels increased significantly whereas IL-12 and (IFN-gamma decreased in both compartments. Mean levels of IL-4 and IL-10 decreased significantly in the serum. There was direct correlation between serum and CVL levels of IL-2 and IL-10. IL-10 had a negative correlation with CD4% at baseline and 6 months of therapy. Mean levels of all alpha- and beta-chemokines decreased in serum after therapy. In CVL, mean levels of MIP-1alpha, RANTES, and IL-8 reduced and SDF-1alpha increased significantly (P value <0.001). Serum levels of all the cytokines, except IL-2, and all chemokines prior to therapy, were significantly higher than healthy controls. In CVL, mean levels of TNF-alpha, IL-6, IL-1beta, IL-12, IFN-gamma, IL-10, RANTES, and IL-8 were significantly higher, whereas IL-2, MIP-1alpha, and MIP-1beta were significantly lower than healthy controls. The mean levels of proinflammatory cytokines and chemokines significantly decreased in serum and CVL after therapy, possibly due to reduced viral load.
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PMID:Effect of non-nucleoside reverse transcriptase inhibitors on cytokine, chemokine, and immunoglobulin profiles in serum and genital secretions of HIV-infected women. 2018 69

The expression of RNA for interleukin (IL) -9, -10 and -12, interferon gamma (IFN-gamma), transforming growth factor beta one (TGF-beta1), macrophage inflammatory protein one alpha (MIP-1alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in a panel of human T leukemia cell lines at various stages of differentiation, and normal thymocytes was examined using reverse transcriptase-polymerase chain reaction (RT-PCR). Fourteen of 16 T cell lines expressed the gene for TGF-beta1 and 12 of the cell lines also expressed the gene for GM-CSF. None of the 5 normal thymocyte samples constitutively expressed RNA for TGF-beta1 or GM-CSF. One cell line established from a patient with adult T cell leukemia (ATL), ED-S-, expressed the genes for TGF-beta1, GM-CSF, IL-10, IL-12, IFN-gamma and MIP-1alpha. IL-9 was not expressed by any cell line, IL-10 was expressed by only three cell lines and IL-12 was expressed by only two cell lines. The production of immunosuppressive factors such as TGF-beta1 by T leukemic cells is a possible mechanism for the clinical progression of this disease.
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PMID:Constitutive expression of immunosuppression-associated cytokine genes in a panel of human T-leukemia-cell lines - high-incidence of transforming growth-factor-Beta gene-expression. 2156 70


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