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 high degree of immunity induced by the bovine lungworm, Dictyocaulus viviparus, makes it an ideal model in which to study nematode-induced protective immune responses. Here, cytokine responses were measured over the course of an experimental infection of D. viviparus. Local cytokine messenger RNA (mRNA) transcripts were measured in lung parenchyma, tracheal rings and draining lymph nodes using semi-quantitative reverse transcriptase-polymerase chain reaction. Responses were measured in animals necropsied at 15, 22 and 43 days post-infection (DPI). The responses elicited at these time points were compared with cytokine levels observed in uninfected animals. Interleukin (IL)-4, IL-5, IL-10, IL-12p35, IL-13 and interferon gamma (IFNgamma) mRNA levels were measured in duplicate at each site. By 42 DPI, very few parasites were recovered, either from faeces or lungs. Transcripts of all cytokines increased in the lung parenchyma, tracheal rings and caudal mesenteric lymph nodes by 15 DPI. The response was rapid and peaked during the time of larval migration through the lungs. By 42 DPI, expression levels of most cytokines were reduced to levels similar to, or below, base line values measured in uninfected animals. Highest levels of IL-10, IL-12p35, IL-13 and IFNgamma transcript were measured in the bronchial lymph nodes of uninfected animals. IgG1 levels were negatively correlated with expression levels of all cytokines. The results demonstrate that a mixed cytokine response occurs over the course of a primary infection during which the parasites were eliminated by day 43 DPI. These results agree with those obtained for other helminths in cattle and challenge the hypothesis that polarised Th2 responses are essential for protection against nematodes in this species. These observations are important in the development of recombinant vaccines, particularly when considering adjuvant choice.
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PMID:Local cytokine responses in Dictyocaulus viviparus infection. 1574 Aug 68

While most human T-cell leukemia virus type-I (HTLV-I)-infected T cells express abundant class II antigens, some aggressive-type adult T-cell leukemia (ATL) cells lose their expression. To investigate the significance of the class II antigen of HTLV-I infected cells, the progressiveness of HTLV-I-infected long-term cultured T-cell lines was evaluated, and then their antigen-presenting capacity was examined using a superantigen, staphylococcus enterotoxin B (SEB). Among the cell lines derived from peripheral blood, HPB-ATL-T (ATL-T), HPB-ATL-2 (ATL-2) and HPB-ATL-O were more progressed than Tax exclusively expressing HPB-CTL-I (CTL-I), because the former deleted p16 gene (polymerase chain reaction (PCR)) and strongly transcribed survivin (reverse transcriptase-PCR). Notably, interferon gamma-independent loss of class II expression of ATL-T and ATL-2 was found. In antigen-presenting experiments, however, both cell lines induced SEB-dependent significant T-cell proliferation estimated by [(3)H] thymidine uptake. No class II-re-expressed ATL-2 cells were observed in the SEB-presenting cultures by indirect immunofluorescence, and only minimum inhibition of SEB-dependent T-cell response by anti-human leukocyte antigen (HLA)-DR monoclonal antibody was observed. These findings suggest that both ATL-T and ATL-2 very effectively present SEB to T cells less dependently on class II molecules. These less immunogenic leukemic cells of aggressive ATL may contribute to disease aggression.
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PMID:Human leukocyte antigen-class II-negative long-term cultured human T-cell leukemia virus type-I-infected T-cell lines with progressed cytological properties significantly induce superantigen-dependent normal T-cell proliferation. 1587 24

Some cutaneous T-cell lymphomas, (CTCLs) clonal T cells are deficient in interferon signaling, making them promising targets for viral oncolysis. We evaluated cytopathic effects of measles virus (MV) in CTCL. CTCL cell lines and infiltrating lymphocytes in CTCL expressed MV receptors CD150 and CD46. In a phase 1 dose escalation trial a total of 16 injections of live MV, Edmonston-Zagreb vaccine strain, were given intratumorally to 5 patients with CTCL. Patients had antimeasles-serum antibodies and were pretreated with interferon-alpha to prevent uncontrolled virus spread. The well-tolerated treatment with MV resulted in clinical responses. Evaluation of biopsies, before and at 11 days after injection, by immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated local viral activity with positive staining for MV nucleoprotein (NP), an increase of the interferon gamma (IFN-gamma)/CD4 and IFN-gamma/CD8 mRNA ratios and a reduced CD4/CD8 ratio. All patients demonstrated an increased antimeasles antibody titer after therapy. The data demonstrate that CTCLs are promising targets for an MV-based oncolytic therapy.
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PMID:Oncolytic measles virus in cutaneous T-cell lymphomas mounts antitumor immune responses in vivo and targets interferon-resistant tumor cells. 1596 18

The pathogenesis of inflammatory bowel disease (IBD) and antibiotic-responsive diarrhea (ARD) in dogs likely involves an interaction between the intestinal immune system and luminal bacterial or food antigens. German Shepherd Dogs (GSD) are particularly predisposed to both IBD and ARD. CD4+ T cells are important for the regulation of immune responses in the mucosa, and they exert their effects through the secretion of cytokines. The present study examined the role of cytokines in the pathogenesis of canine chronic enteropathies by quantification of mRNA encoding interleukin-2 (IL-2), IL-4, IL-5, IL-6, IL-10, IL-12, IL-18, interferon gamma, tumor necrosis factor-alpha, transforming growth factor-beta, and glyceraldehyde-3-phosphate dehydrogenase by real-time reverse transcriptase polymerase chain reaction in duodenal mucosal biopsies obtained from 39 dogs with chronic diarrhea and 18 control dogs. Contemporaneously collected biopsies were assessed for histologic changes with a 4-point grading system. No significant difference in the expression of cytokine mRNA (P > .01) was detected between dogs with and those without chronic diarrhea. Similarly, no significant differences in cytokine mRNA expression were observed between GSD and other breeds with chronic diarrhea, or between histologically normal duodenal mucosa and that with evidence of inflammatory change. Failure to detect a difference in mRNA expression does not rule out the possibility of a defect downstream at the level of translation or protein function. No conclusion can be drawn from these data as to the predominant CD4+ cell type in the pathogenesis of these canine chronic enteropathies.
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PMID:Cytokine mRNA quantification in duodenal mucosa from dogs with chronic enteropathies by real-time reverse transcriptase polymerase chain reaction. 1623 8

Cytokine deviation may be a factor contributing to graft acceptance. We analyze, in the context of liver transplantation, circulating cytokine levels and their mRNA precursors in liver biopsy samples to study a putative correlation with early immunologic outcome. Forty primary pediatric liver recipients were submitted to a prospective immune monitoring protocol, including 8 of 40 patients with an early, biopsy-proven acute rejection episode. The 32 patients with graft acceptance showed markedly increased interleukin (IL)-10 blood levels at 2 hours after reperfusion on days 1 and 4 after transplantation as compared with baseline, whereas patients with graft rejection only exhibited increased IL-10 levels at 2 hours. A good correlation was observed between IL-10 peripheral levels and levels ascertained by IL-10 reverse transcriptase-polymerase chain reaction at 2 hours and on day 7. Patients with graft acceptance also showed a decrease in interferon gamma (IFN-gamma) at 1 and 2 hours after reperfusion on days 1, 4, 7, 14, and 28 after transplantation. One patient with graft tolerance who had subsequent immunosuppression withdrawal after posttransplantation lymphoproliferative disease showed a similar intraoperative IL-10 pattern, whereas posttransplantation tumor necrosis factor alpha and IFN-gamma levels greatly decreased. The occurrence of cytokine immune deviation may therefore be related to early graft acceptance in children who receive liver transplants.
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PMID:Early immunological monitoring after pediatric liver transplantation: cytokine immune deviation and graft acceptance in 40 recipients. 1731 67

To evaluate the role of IFN-gamma (interferon gamma) in IL-12- (interleukin-12)-induced inhibition of the inflammatory response in the eye during endotoxin-induced uveitis (EIU). C57BL/6 wild type mice and IFN-gamma-deficient (GKO) mice were injected with 250 microg of Salmonella typhymurium endotoxin as a model for EIU. Animals were then injected intraocularly with 100 ng of rIL-12 or the equivalent volume of Phosphate-buffer saline (PBS). Histopathologic grading of disease was performed 12, 36 and 72 h after endotoxin injection. Chemokine mRNA expression in the eye was evaluated by reverse transcriptase-polymerase chain reaction. Depletion of NK1.1+ cells in vivo was performed using a PK136 antibody. Depletion of IFN-gamma was performed using the R4-6A2 antibody. C57BL/6 mice treated with rIL-12 intraocularly were protected from the development of EIU. Neutralization of IFN-gamma with a monoclonal antibody abrogated such protection. The IL-12 protective effects were lost in NK1.1-depleted mice. Intraocular IL-12 decreased the expression of keratinocyte-derived chemokines (KC) gene but had no effect on macrophage inflammatory protein (MIP-2) gene. The protective effect of IL-12 during EIU occurs through production of IFN-gamma by NK1.1+ cells. IL-12-induced higher levels of IFN-gamma are also correlated with lower expression of the chemokine KC, resulting in diminished attraction of neutrophils to the inflammatory site.
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PMID:NK1.1 cells downregulate murine endotoxin-induced uveitis following intraocular administration of interleukin-12. 1763 10

Molecular abnormalities in the epithelial cells of endometriosis and their relevance to carcinogenesis of the ovary have been well studied. On the other hand, the differences of proinflammatory microenvironments between endometriosis and ovarian carcinomas have not been well documented yet. In this study, the expression patterns of CXC chemokines (IL-8, ENA-78, GRO-alpha, I-TAC, Mig, and SDF-1) and their receptors (CXCR2, CXCR3, and CXCR4) were compared among 12 ovarian carcinomas, 8 endometriosis, and 6 normal ovaries using quantitative reverse transcriptase polymerase chain reaction and immunohistochemistry. The CXCR3-mediated signaling in ovarian carcinoma cells in vitro was also investigated. In quantitative reverse transcriptase polymerase chain reaction, ENA-78 was up-regulated both in endometriosis and carcinomas, whereas I-TAC was detected exclusively in carcinomas. CXCR3 was up-regulated both in carcinomas and endometriosis. However, immunohistochemical studies revealed that the localization of CXCR3 in carcinomas was distinctively different from that in endometriosis. In carcinoma-endometriosis coexisting cases, CXCR3-positive lymphocytes in benign lesions decreased in proportion as CXCR3-positive tumor cells replaced the tissues. CXCR3 was also detected in ovarian carcinoma cell lines in vitro. Administration of interferon gamma (IFN-gamma)-inducible chemokines induced extracellular signal-regulated kinase phosphorylation in these carcinoma cells. The results indicated that CXC chemokines might contribute to the progression of ovarian carcinomas and endometriosis in different manners. Aberrant expression of IFN-gamma-inducible chemokines and CXCR3 in carcinoma cells in association with reduced CXCR3-positive immune cells raised the possibility that IFN-gamma-inducible chemokines might not exert effective antitumor immune responses but that they might work in favor of tumor progression.
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PMID:Up-regulation of CXC chemokines and their receptors: implications for proinflammatory microenvironments of ovarian carcinomas and endometriosis. 1770 63

Biphalin, a dimeric enkephalin analog, is under investigation as a potential, long-lasting medication of pain associated with chronic diseases, like cancer or AIDS. The role of cytokines, and splenocytes in anti-Friend leukemia virus (FLV) activity of biphalin, a synthetic opioid, and AZT was investigated in vitro. Mouse splenocytes inhibited FLV replication in Mus dunni (Dunni) cells when they were added to the cell culture. This inhibitory effect of splenocytes also was evident when cells were combined with biphalin and AZT as measured using a focus-forming assay. Under cell-free conditions, recombinant interferon gamma (IFNgamma), interleukin 2 (IL-2) and IL-4 directly inhibited the FLV reverse transcriptase (RT) activity by 27% to 36%. IFNgamma at 0.005 pg to 500 ng inhibited FLVRT activity by 61% to 80%. Acombination of 250 ng IFNgamma and 50 mug biphalin resulted in a 94% reduction of FLVRT activity, as compared with 61% inhibition by IFNgamma alone. The combination of AZT and IFNgamma, IL-2 or IL-4 also induced a stronger suppression of FLV RT activity than either cytokine or AZT used alone. In addition, cloned RT from Moloney murine leukemia virus (MMLV) was directly sensitive to inhibition by biphalin. Thus, the anti-FLV effects of splenocytes in combination with biphalin and AZT in cell culture are likely mediated to a large degree by the direct effect of cytokines. This antiviral activity of splenocytes or cytokines combined with chemotherapy, biphalin, and/or AZT, could be used as a complementary therapy to current approaches for retroviral infection and benefit acquired immunodeficiency syndrome (AIDS) patients. In conclusion, biphalin applied primarily as a new medicine for chronic pain treatment in AIDS patients may play a significant beneficial role as a component of antiviral HIV multidrug therapies.
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PMID:Molecular assessment of the potential combination therapy of cytokines with biphalin and AZT for Friend leukemia virus infection in vitro. 1844 80

High prevalence of hepatitis B virus (HBV) infection in China offers a unique setting to examine HBV's influence on the presentation of dengue fever. In 398 patients admitted for suspected dengue fever, 89% (353/398) were positive for dengue IgM antibodies. Among dengue-infected patients, 8% (29/353) had chronic HBV co-infection. Only dengue virus serotype 1 was identified by virus isolation and reverse transcriptase-polymerase chain reaction assays. No case of dengue hemorrhagic fever/dengue shock syndrome was diagnosed. In addition to routine clinical tests, interleukin 2 (IL-2), IL-4, IL-6, IL-10, interferon gamma (IFNgamma), and tumor necrosis factor alpha (TNFalpha) levels were measured in the sera of 95% (334/353) of dengue-infected subjects as well as controls. Surprisingly, HBV/dengue co-infected patients made less IL-6 (P < 0.05) and TNFalpha (P < 0.05) than patients with only dengue infection. Similar levels of IL-4, IL-10, and IFNgamma were found in both groups. Thus, HBV co-infection seems to alter the cytokine production pattern when patients contract dengue infection.
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PMID:Unique impacts of HBV co-infection on clinical and laboratory findings in a recent dengue outbreak in China. 1868 15


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