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)

Synthetic oligodeoxyribonucleotides (ODNs) designed to selectively inhibit the transcription or translation of specific genes are being used to modulate the activity of the targeted gene. Because multiple copies of mRNA can be transcribed from one actively expressed gene, ODNs that target double-stranded DNA and form triple helices upon binding with the gene itself have an advantage over ODNs that target the gene product (mRNA) in an antisense fashion. For the present studies, we designed four different triple helix-forming phosphodiester ODNs (TFOs) targeted to the tumor necrosis factor (TNF) gene and examined their effect on production of TNF and on cellular growth of tumors in which TNF acts as an autocrine growth factor. The ODNs J-109-50 and J-108-57 were designed to interact with polypurine oligonucleotides corresponding to the binding sites for nuclear factors kB (-237 to -208) and Sp1 (-58 to -33), respectively; J111-51 was designed to interact with a polypurine oligonucleotide in the third intron (+1429 to +1456) of the TNF gene. To enhance the cellular penetration and prevent degradation by cellular nucleases, the TFOs were modified at their 3' ends by either a cholesterol side chain or a propanolamine blocking group. Treatment of the human promonocytic cell line THP-1 with TNF-TFOs at a nontoxic concentration (2 microM) reduced the production of TNF. All of the TNF-TFOs tested were effective, and control-irrelevant TFOs were ineffective in inhibiting TNF production. The activity of the most efficacious TNF-TFOs also correlated with a decrease in TNF mRNA as observed by using reverse transcriptase PCR assays. In several tumors in which TNF acts as an autocrine growth factor, we examined the antiproliferative activity of J111-51. We found that in the human glioblastoma tumor cell line U-251, TNF-induced growth was blocked by J111-51 in a dose-dependent manner. Thus, overall results demonstrate that oligonucleotides directed to the specific regions of TNF can be designed, which may have a potential in cancer therapy.
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PMID:Triple helix-forming oligodeoxyribonucleotides targeted to the human tumor necrosis factor (TNF) gene inhibit TNF production and block the TNF-dependent growth of human glioblastoma tumor cells. 891 51

To identify the host genes induced or suppressed by infection of mycobacteria, the reverse transcriptase polymerase chain reaction (RT-PCR) and the differential display reverse transcriptase polymerase chain reaction (DD RT-PCR) methods were used. In this study, cDNAs complement to mRNA extracted from human peripheral monocyte derived naive THP-1 cells, THP-1 cells infected with live Mycobacterium bovis BCG, THP-1 cells treated with heat-killed BCG, and THP-1 cells incubated with IgG-coated glass-beads were compared on the sequencing gel. One (TG2-1) of the clones selected by DD RT-PCR is 446 bp long and is identical to human ferritin heavy (H) chain gene. Northern blot analysis confirmed that ferritin H chain gene has been markedly over-expressed in monocytic THP-1 cells incubated with live and dead M. bovis BCG. Differential display techniques of host genes whose expression levels were varied by infection of mycobacteria could provide information about the response of macrophages to mycobacterial infection.
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PMID:Differential expression of ferritin heavy chain in THP-1 cells infected with Mycobacterium bovis BCG. 941 6

In addition to its inhibitory activity against viral DNA polymerases and reverse transcriptase, the acyclic nucleoside phosphonate 9-(2-phosphonylmethoxyethyl)adenine (PMEA) also markedly inhibits the replicative cellular DNA polymerases alpha, delta, and epsilon. We have previously shown that PMEA is a strong inducer of differentiation in several in vitro tumor cell models and has marked antitumor potential in vivo. To elucidate the molecular mechanism of the differentiation-inducing activity of PMEA, we have now investigated the effects of the drug on cell proliferation and differentiation, cell cycle regulation, and oncogene expression in the human erythroleukemia K562 cell line. Terminal, irreversible erythroid differentiation of PMEA-treated K562 cells was evidenced by hemoglobin production, increased expression of glycophorin A on the K562 cell membrane, and induction of acetylcholinesterase activity. After exposure to PMEA, K562 cell cultures displayed a marked retardation of S-phase progression, leading to a severe perturbation of the normal cell cycle distribution pattern. Whereas no substantial changes in c-myc mRNA levels and p21, PCNA, cdc2, and CDK2 protein levels were noted in PMEA-treated K562 cells, there was a marked accumulation of cyclin A and, most strikingly, cyclins E and B1. A similar picture of cell cycle deregulation was also observed in PMEA-exposed human myeloid THP-1 cells. However, in contrast to the strong differentiation-inducing activity of PMEA in K562 cells, the drug completely failed to induce monocytic maturation of human myeloid THP-1 cells. On the contrary, THP-1 cells underwent apoptotic cell death in the presence of PMEA, as demonstrated by prelytic, intracellular DNA fragmentation and the binding of annexin V to the cell surface. We hypothesize that, depending on the nature of the tumor cell line, PMEA triggers a process of either differentiation or apoptosis by the uncoupling of normally integrated cell cycle processes through inhibition of DNA replication during the S phase.
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PMID:9-(2-Phosphonylmethoxyethyl)adenine induces tumor cell differentiation or cell death by blocking cell cycle progression through the S phase. 1039 5

An elevation in plasma estrogen levels is believed to play a key role in the pathogenesis of breast cancer. The conversion of estradiol-17beta (E2) to estrone (E1) by 17beta-hydroxy steroid dehydrogenase type 4 (17-HSD4) represents a major pathway of its inactivation in cells. In this study the potential relationship between lipoprotein peroxidation products and E2 metabolism was examined. It was noted that oxidized low-density lipoprotein (OX-LDL), not native LDL, caused a time- and concentration-dependent inhibition of the conversion of labeled E2 to E1 in THP-1 macrophage cells. Further studies noted that among the lipoprotein peroxidation products examined, malondialdehyde (MDA) caused a marked decrease in this reaction, whereas hexanal and a variety of oxysterols had no effect. This inhibition of E1 formation from E2 in THP-1 cells was confirmed by the quantitation of estrone formed with high-pressure liquid chromatography and by the expression of 17-HSD4 by reverse transcriptase-polymerase chain reaction. MDA added to Hep G2 cells showed a similar trend in E1 formation. These results suggest that increased oxidative stress and lipid peroxidation might result in decreased inactivation of biologically active estrogen. This might be important in postmenopausal women undergoing estrogen replacement therapy.
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PMID:Evidence for interference in estradiol-17beta inactivation to estrone by oxidized low-density lipoprotein and selected lipid peroxidation products. 1048 10

Genes induced or suppressed by oxidized low-density lipoproteins (oxLDL) in human monocytic THP-1 cells were searched using differential display reverse transcriptase polymerase chain reactions (DDRT-PCR). Among the many differentially expressed cDNA fragments, one was dramatically stimulated by the oxLDL in a steady state level, which was later found to contain sequences corresponding to ferritin light chain (L-ferritin) in a sequence homology search. The stimulatory effect of the oxLDL on the level of L-ferritin mRNA in the THP-1 cells was both time- and dose-dependent. When the cells were allowed to differentiate in the presence of phorbol 12-myristate 13-acetate (PMA), the differentiated cells were generally less responsive to the oxLDL than the undifferentiated ones. An increase of L-ferritin mRNA was observed when the cells were treated with the lipid components in the oxLDL such as 9-HODE, 13-HODE, and 25-hydroxycholesterol. In addition, a stimulation of the L-ferritin gene expression was also observed when the cells were treated with an endogenous peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, 15d-PGJ2, in a time- and dose-dependent manner. These results suggest that oxLDL or its constituents are related to the stimulation of L-ferritin expression via PPARgamma.
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PMID:Regulation of ferritin light chain gene expression by oxidized low-density lipoproteins in human monocytic THP-1 cells. 1055 12

The cysteine-rich region of the 170-kDa subunit galactose-adherence lectin (Gal-lectin) of Entamoeba histolytica is a subunit vaccine candidate and a protective antigen in the gerbil model of amebiasis. Macrophage-mediated immunity is important for protection against E. histolytica and is activated by Th1 cytokines. As Th1 differentiation is promoted by IL-12, we investigated what portion of the Gal-lectin could stimulate IL-12 in human THP-1 macrophages. Native Gal-lactin stimulated IL-12 p40 / p35 mRNA expression in a dose- and time-dependent manner as measured by reverse transcriptase-PCR. Human immune serum and Gal-lectin mAb inhibition studies identified amino acids (aa) 596 - 998 as immunogenic and containing the IL-12 inducing domain. IFN-gamma priming augmented Gal-lectin-induced IL-12 mRNA expression independent of TNF-alpha and IL-1beta, and was required for IL-12 p70 protein production from macrophages and human peripheral blood mononuclear cells. Gal-lectin plus IFN-gamma stimulated IL-12 p40 and p35 gene transcription with stable mRNA transcripts and a differential requirement for protein synthesis. These results suggest that aa 596 - 998 of the Gal-lectin can confer Th1-mediated protection against amebiasis through IL-12 induction.
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PMID:A subunit vaccine candidate region of the Entamoeba histolytica galactose-adherence lectin promotes interleukin-12 gene transcription and protein production in human macrophages. 1067 Nov 97

Previously, we reported that Malassezia furfur, causing systemic fungal infection, was taken up into human monocytic cell line, THP-1, in a concentration-dependent manner. This fact suggested that M. furfur could activate phagocytes, such as monocyte and polymorphonuclear leukocyte. Thus we examined cytokine mRNA expression from human monocytic and granulocytic cell line, THP-1 and HL-60, stimulated with M. furfur by using reverse transcriptase-polymerase chain reaction (RT-PCR) and ELISA. We chose IL-1alpha, IL-6, IL-8, IL-12 and TNF-alpha as primers for THP-1, and IL-1alpha, IL-6 and IL-8 for HL-60. M. furfur induced the expression of IL-8 mRNA from THP-1 and HL-60 following incubation for 3 h, and also induced IL-1alpha mRNA from HL-60, although this induction was weaker than that of IL-8 mRNA. Furthermore, opsonized M. furfur induced stronger expression of IL-8 mRNA in comparison with intact M. furfur. IL-8 production from THP-1 and HL-60 was enhanced in a concentration- and incubation time-dependent manner. These facts strongly suggested that M. furfur could activate phagocytes, and could induce inflammatory responses in systemic infection.
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PMID:Enhancement of IL-8 production from human monocytic and granulocytic cell lines, THP-1 and HL-60, stimulated with Malassezia furfur. 1079 7

Familial Mediterranean fever (FMF) is a recessive disorder characterized by episodes of fever and neutrophil-mediated serosal inflammation. We recently identified the gene causing FMF, designated MEFV, and found it to be expressed in mature neutrophils, suggesting that it functions as an inflammatory regulator. To facilitate our understanding of the normal function of MEFV, we extended our previous studies. MEFV messenger RNA was detected by reverse transcriptase-polymerase chain reaction in bone marrow leukocytes, with differential expression observed among cells by in situ hybridization. CD34 hematopoietic stem-cell cultures induced toward the granulocytic lineage expressed MEFV at the myelocyte stage, concurrently with lineage commitment. The prepromyelocytic cell line HL60 expressed MEFV only at granulocytic and monocytic differentiation. MEFV was also expressed in the monocytic cell lines U937 and THP-1. Among peripheral blood leukocytes, MEFV expression was detected in neutrophils, eosinophils, and to varying degrees, monocytes. Consistent with the tissue specificity of expression, complete sequencing and analysis of upstream regulatory regions of MEFV revealed homology to myeloid-specific promoters and to more broadly expressed inflammatory promoter elements. In vitro stimulation of monocytes with the proinflammatory agents interferon (IFN) gamma, tumor necrosis factor, and lipopolysaccharide induced MEFV expression, whereas the antiinflammatory cytokines interleukin (IL) 4, IL-10, and transforming growth factor beta inhibited such expression. Induction by IFN-gamma occurred rapidly and was resistant to cycloheximide. IFN-alpha also induced MEFV expression. In granulocytes, MEFV was up-regulated by IFN-gamma and the combination of IFN-alpha and colchicine. These results refine understanding of MEFV by placing the gene in the myelomonocytic-specific proinflammatory pathway and identifying it as an IFN-gamma immediate early gene.
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PMID:The gene for familial Mediterranean fever, MEFV, is expressed in early leukocyte development and is regulated in response to inflammatory mediators. 1080 93

We found that human herpesvirus 8-encoded IL-6 (vIL-6) induced endogenous human IL-6 (huIL-6) secretion from various cell lines (MT-4, THP-1, U937, Raji, and CESS) including patients with multicentric Castleman's disease. Especially, in MT-4 cells, huIL-6 was enhanced with vIL-6 by 30-fold compared with that of control. In addition, reverse transcriptase-polymerase chain reaction confirmed that vIL-6 induced huIL-6 expression in MT-4 cells. Our novel finding of the huIL-6 induction by vIL-6 indicates that vIL-6 may play a significant role in the pathogenesis of HHV-8 associated diseases.
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PMID:Human herpesvirus 8-encoded interleukin-6 homologue (viral IL-6) induces endogenous human IL-6 secretion. 1086 41

Ureaplasma urealyticum is relatively common in the respiratory tract of very low birth weight infants and has been hypothesized to be involved in the development of chronic lung disease. The purpose of this study was to investigate whether U. urealyticum could stimulate macrophages to produce proinflammatory cytokines in vitro, which are early pathologic changes in the lung during the development of chronic lung disease. A human monocytic cell line (THP-1) differentiated to macrophages, a rat alveolar macrophage cell line (Nr8383), and human lung macrophages from tracheobronchial aspirate fluid in preterm infants were exposed to U. urealyticum antigen for 24 h. The protein levels of human IL-6, tumor necrosis factor-alpha (TNF-alpha), and rat TNF-alpha were measured with ELISA. Rat IL-6 was analyzed with a specific bioassay. The mRNA levels of these cytokines were detected by reverse transcriptase-PCR. The production of TNF-alpha and IL-6 increased after stimulation with U. urealyticum in both the human and rat macrophage cell lines. In tracheobronchial aspirate fluid macrophages, U. urealyticum increased the production of TNF-alpha from 14 to 84% and IL-6 from 46 to 268% above control levels. U. urealyticum also induced gene expression of TNF-alpha and IL-6. In conclusion, U. urealyticum could be an important factor in the development of chronic lung disease because of its ability to induce alveolar macrophage proinflammatory cytokine production.
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PMID:Ureaplasma urealyticum-induced production of proinflammatory cytokines by macrophages. 1087 9


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