28 results on '"Sancéau J"'
Search Results
2. Évaluation des pratiques de prescriptions des établissements de santé du Berry lors de la délivrance de produits sanguins labiles
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Sapey, T., Poirier-Cajat, C., Desmaisons, C., Rongere, D., Sanceau, J., and Lele, I.
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- 2017
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3. Évolution des non-conformités des demandes de produits sanguins labiles après sensibilisation des prescripteurs du département de l’Indre
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Sapey, T., Sanceau, J., and Py, J.-Y.
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- 2017
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4. Évolution des non-conformités (NC) des demandes de produits sanguins labiles (PSL) après sensibilisation des prescripteurs du département de l’Indre
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Sapey, T., Py, J.-Y., Sanceau, J., and Dehaut, F.
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- 2015
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5. Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha
- Author
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Sancéau, J, Falcoff, R, Beranger, F, Carter, D B, and Wietzerbin, J
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Interleukin-6 ,Tumor Necrosis Factor-alpha ,Gene Expression ,Humans ,RNA ,Drug Synergism ,Blotting, Northern ,Acetylmuramyl-Alanyl-Isoglutamine ,Cells, Cultured ,Monocytes ,Research Article - Abstract
We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3.4 kb and 1.6 kb were easily detected at 2.5 hr of culture and remained stable until 18 hr. In MDP-treated monocytes, three IL-6 RNA species displayed different kinetics of accumulation: a 3.4 kb RNA whose expression already reached its maximum after 2.5 hr exposure to MDP; a 1.6 kb RNA whose expression peaked at 5 hr; and a new RNA species of 1.4 kb which was transiently induced in early time of cell stimulation. TNF-alpha co-operated with MDP to increase IL-6 gene expression and secretion of biological active protein (measured by the hybridoma plasmacytoma growth factor assay). MDP exhibits a broad spectrum of immunomodulation properties such as adjuvant activity, enhancement of macrophage cytotoxicity against tumour and induction of non-specific resistance to intracellular agents. The results reported here suggest that these properties might be linked to the stimulation by MDP of genes coding for key cytokines such as IL-6, TNF and IL-1.
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- 1990
6. Secretion of interleukin-6 (IL-6) by human monocytes stimulated by muramyl dipeptide and tumour necrosis factor alpha.
- Author
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Sancéau, J., Falcoff, R., Beranger, F., Carter, D. B., and Wietzerbin, J.
- Subjects
- *
LEUCOCYTES , *INTERLEUKIN-6 , *TUMORS , *MONOCYTES , *GENETIC regulation , *CELLULAR immunity - Abstract
We studied IL-6 gene expression in human monocytes stimulated by muramyl dipeptide (MDP), a synthetic immunomodulator derived from mycobacterial cell walls. In control monocytes, two IL-6 transcripts of 3-4 kb and U6 kb were easily detected at 2-5 hr of culture and remained stable until 18 hr. In MDP-treated monocytes, three IL-6 RNA species displayed different kinetics of accumulation: a 3.4 kb RNA whose expression already reached its maximum after 2.5 hr exposure to MDP; a 1.6 kb RNA whose expression peaked at 5 hr; and a new RNA species of 1.4 kb which was transiently induced in early time of cell stimulation. TNF-α co-operated with MDP to increase IL-6 gene expression and secretion of biological active protein (measured by the hybridoma plasmacytoma growth factor assay). MDP exhibits a broad spectrum of immunomodulation properties such as adjuvant activity, enhancement of macrophage cytotoxicity against tumour and induction of non- specific resistance to intracellular agents. The results reported here suggest that these properties might be linked to the stimulation by M DP of genes coding for key cytokines such as IL-6, TNF and IL- I. [ABSTRACT FROM AUTHOR]
- Published
- 1990
7. RECOVERY BY INTERFERON OF MENGOVIRUS-INDUCED SHUTOFF OF HOST PROTEIN SYNTHESIS*.
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Falcoff, R., Sancéau, J., Aujean, O., and Vaquero, C.
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- 1980
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8. Intracellular human gamma-interferon triggers an antiviral state in transformed murine L cells.
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Sancéau, J, Sondermeyer, P, Béranger, F, Falcoff, R, and Vaquero, C
- Abstract
Interaction of human gamma-interferon (IFN-gamma) with a cell-surface receptor is known to be essential for the cell to become resistant to viral infection. Here we demonstrate that IFN-gamma, when present inside the cell, is also capable of inducing a permanent antiviral state. Mouse cells transformed with a truncated human cDNA encoding a mature IFN-gamma protein lacking the signal peptide accumulate high levels of intracellular human IFN-gamma. Not only do these cells acquire a permanent resistance to viral infection, they also exhibit all the biochemical characteristics normally observed after exposure to exogenous IFN. The observed loss of species specificity normally associated with IFN-gamma suggests that this restriction is strictly dependent on the interaction of the molecule with the cell-surface receptor.
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- 1987
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9. Triggering of the human interleukin-6 gene by interferon-gamma and tumor necrosis factor-alpha in monocytic cells involves cooperation between interferon regulatory factor-1, NF kappa B, and Sp1 transcription factors.
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Sancéau, J, Kaisho, T, Hirano, T, and Wietzerbin, J
- Abstract
We investigated the molecular basis of the synergistic induction by interferon-gamma (IFN-gamma)/tumor necrosis factor-alpha (TNF-alpha) of human interleukin-6 (IL-6) gene in THP-1 monocytic cells, and compared it with the basis of this induction by lipopolysaccharide (LPS). Functional studies with IL-6 promoter demonstrated that three regions are the targets of the IFN-gamma and/or TNF-alpha action, whereas only one of these regions seemed to be implicated in LPS activation. The three regions concerned are: 1) a region between -73 and -36, which is the minimal element inducible by LPS or TNF-alpha; 2) an element located between -181 and -73, which appeared to regulate the response to IFN-gamma and TNF-alpha negatively; and 3) a distal element upstream of -224, which was inducible by IFN-gamma alone. LPS signaling was found to involve NF kappa B activation by the p50/p65 heterodimers. Synergistic induction of the IL-6 gene by IFN-gamma and TNF-alpha, in monocytic cells, involved cooperation between the IRF-1 and NF kappa B p65 homodimers with concomitant removal of the negative effect of the retinoblastoma control element present in the IL-6 promoter. This removal occurred by activation of the constitutive Sp1 factor, whose increased binding activity and phosphorylation were mediated by IFN-gamma.
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- 1995
10. Expression of extracellular and intracellular human IFN-γ in mouse L cells transformed with the human IFN-γ cDNA gene
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Sancéau, J., primary, Lewis, J.A., additional, Sondermeyer, P., additional, Beranger, F., additional, Falcoff, R., additional, and Vaquero, C., additional
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- 1986
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11. Interferon-β2(BSF-2) mRNA Is Expressed in Human Monocytes
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SANCÉAU, J., primary, FALCOFF, R., additional, ZILBERSTEIN, A., additional, BÉRANGER, F., additional, LEBEAU, J., additional, REVEL, M., additional, and VAQUERO, C., additional
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- 1988
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12. Downregulation of angiogenic factors in Ewing tumor xenografts by the combination of human interferon-alpha or interferon-beta with ifosfamide.
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Sancéau J and Wietzerbin J
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- Animals, Base Sequence, DNA Primers, Enzyme-Linked Immunosorbent Assay, Female, Humans, Ifosfamide administration & dosage, Interferon-alpha administration & dosage, Interferon-beta administration & dosage, Matrix Metalloproteinase 9 genetics, Matrix Metalloproteinase 9 metabolism, Mice, Mice, Nude, RNA, Messenger metabolism, Sarcoma, Ewing enzymology, Sarcoma, Ewing pathology, Transplantation, Heterologous, Vascular Endothelial Growth Factor A genetics, Vascular Endothelial Growth Factor A metabolism, Angiogenesis Inducing Agents metabolism, Down-Regulation drug effects, Ifosfamide pharmacology, Interferon-alpha pharmacology, Interferon-beta pharmacology, Sarcoma, Ewing metabolism
- Abstract
Ewing sarcoma is the second most common bone tumor in childhood. Despite aggressive chemotherapy and radiotherapy, the prognosis of metastatic disease remains poor. In a nude mouse model of Ewing tumor xenografts, we recently showed that human type I interferons (IFNs) inhibit the growth of established xenografts. Combined therapy with human IFNs and ifosfamide (IFO), an alkylating agent widely used in high-dose chemotherapy of Ewing tumors, results in a strong synergistic antitumor effect. We have investigated the effect of IFNs/IFO treatment on the expression of vascular endothelial growth factor (VEGF), matrix metalloproteinase 9 (MMP-9), and urokinase plasminogen activator receptor (uPAR), three key mediators of tumor growth and angiogenesis, in tumor xenografts generated either from a primary tumor (EW7) or from a metastatic tumor (COH). COH tumors expressed 5-fold higher levels of VEGF than EW7 tumors. IFNs/IFO treatment reduced by >70% the amount of VEGF in COH and EW7 tumors. We did not detect constitutive MMP-9 activity in EW7 tumors. In contrast, the metastasis-derived COH tumor expressed very high levels of active MMP-9. Although the total amount of MMP-9 remained unchanged, active MMP-9 was reduced by up to 75% in IFNs/IFO-treated COH tumors. IFNs/IFO treatment triggered in both COH and EW7 tumors the downregulation of uPAR expression, a molecule involved in vascularization and endothelial cell migration. Our results partly explain the mechanism of tumor growth inhibition by IFNs/IFO therapy and provide a rational foundation for the development of a new therapeutic approach to Ewing tumors resistant to conventional chemotherapy.
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- 2004
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13. Matrix metalloproteinase-9 silencing by RNA interference triggers the migratory-adhesive switch in Ewing's sarcoma cells.
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Sancéau J, Truchet S, and Bauvois B
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- Cadherins metabolism, Cell Adhesion, Cell Line, Tumor, Cell Movement, Collagen metabolism, Cytoskeletal Proteins metabolism, Cytoskeleton metabolism, Dose-Response Relationship, Drug, Enzyme Inhibitors pharmacology, Enzyme-Linked Immunosorbent Assay, Extracellular Matrix metabolism, Fibronectins metabolism, Flow Cytometry, Genes, p53, Humans, Laminin metabolism, Microscopy, Confocal, Microscopy, Fluorescence, Models, Biological, Protein Binding, RNA, Messenger metabolism, Subcellular Fractions metabolism, Time Factors, Trans-Activators metabolism, beta Catenin, Gene Silencing, Matrix Metalloproteinase 9 metabolism, RNA Interference, Sarcoma, Ewing metabolism
- Abstract
Enhanced expression of (pro)matrix metalloproteinase-9 (MMP-9) is associated with human tumor invasion and/or metastasis. COH cells derived from a highly invasive and metastatic Ewing's sarcoma constitutively express proMMP-9. Transfection of a double stranded RNA that targets the MMP-9 mRNA into COH cells depleted the corresponding mRNA and protein as demonstrated by reverse transcriptase-PCR, enzyme-linked immunosorbent assay, and gelatin zymography. proMMP-9 extinction resulted in the following: (i) decreased spreading on extracellular matrix (fibronectin, laminin, collagen IV)-coated surfaces, (ii) inhibition of migration toward fibronectin, and (iii) induced aggregation, which was specifically disrupted by a function-blocking E-cadherin antibody. MMP-9 knockdown concomitantly resulted in increased levels of surface E-cadherin, redistribution at the plasma membrane of beta-catenin, and its physical association with E-cadherin. Moreover, induction of E-cadherin-mediated adhesion was associated with RhoA activation and changes in paxillin cytoskeleton. Finally, an inhibitor of gelatinolytic activity of pro-MMP9 did not reduce COH cell migration confirming that the enzymatic property of COH MMP-9 was not required for migration toward fibronectin. Overall, our observations define a novel critical role for proMMP-9 in providing a cellular switch between stationary and migratory cell phases.
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- 2003
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14. Strong inhibition of Ewing tumor xenograft growth by combination of human interferon-alpha or interferon-beta with ifosfamide.
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Sancéau J, Poupon MF, Delattre O, Sastre-Garau X, and Wietzerbin J
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- Animals, Antineoplastic Agents, Alkylating administration & dosage, Antineoplastic Combined Chemotherapy Protocols, Bone Neoplasms metabolism, Bone Neoplasms pathology, DNA-Binding Proteins drug effects, DNA-Binding Proteins metabolism, Female, Humans, Ifosfamide administration & dosage, Interferon-alpha administration & dosage, Interferon-beta administration & dosage, Mice, Mice, Nude, STAT1 Transcription Factor, Sarcoma, Ewing metabolism, Sarcoma, Ewing pathology, Trans-Activators drug effects, Trans-Activators metabolism, Xenograft Model Antitumor Assays, Bone Neoplasms drug therapy, Sarcoma, Ewing drug therapy
- Abstract
Ewing sarcoma is the second most common bone tumor in childhood. Despite aggressive chemotherapy and radiotherapy strategies, the prognosis of patients with metastatic disease remains poor. We have recently reported that Ewing tumor cell proliferation was strongly inhibited by IFN-beta and to a lesser degree by IFN-alpha. Moreover, under IFN-beta treatment, some cell lines undergo apoptosis. Since the possibility of using IFNs for Ewing tumor treatments may be of interest, we have evaluated the efficacy of Hu-IFNs in a nude mice model of Ewing tumor xenografts. The results reported here show that human type I IFNs, Hu-IFN-alpha and Hu-IFN-beta impaired tumor xenograft take and displayed an anti-growth effect toward established xenografts. Furthermore, we have also shown that combined therapy with Hu-IFNs and ifosfamide (IFO), an alkylating agent widely used in high-dose chemotherapy of Ewing tumors, results in a strong antitumor effect. Pathological analysis showed that Hu-IFN-alpha/IFO and Hu-IFN-beta/IFO were characterized by a dramatic decrease in the mitotic index and marked necrosis, as well as extensive fibrosis associated with numerous calcifications. To our knowledge, this is the first demonstration of a potential antitumor effect of human type I IFNs and IFO on Ewing tumors, providing a rational foundation for a promising therapeutic approach to Ewing sarcoma.
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- 2002
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15. Interferons inhibit tumor necrosis factor-alpha-mediated matrix metalloproteinase-9 activation via interferon regulatory factor-1 binding competition with NF-kappa B.
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Sancéau J, Boyd DD, Seiki M, and Bauvois B
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- Base Sequence, Binding, Competitive, DNA Primers, Enzyme Activation, Gene Expression Regulation, Enzymologic physiology, Humans, Interferon Regulatory Factor-1, Matrix Metalloproteinase 9 genetics, Promoter Regions, Genetic, STAT1 Transcription Factor, Sarcoma, Ewing enzymology, Sarcoma, Ewing metabolism, Sarcoma, Ewing pathology, Trans-Activators metabolism, Transcription, Genetic physiology, DNA-Binding Proteins metabolism, Interferons physiology, Matrix Metalloproteinase 9 metabolism, NF-kappa B metabolism, Phosphoproteins metabolism, Tumor Necrosis Factor-alpha physiology
- Abstract
Enhanced expression of matrix metalloproteinase-9 (MMP-9) correlates with invasion during tumor progression. Interferons (IFNs) inhibit MMP-9 activation in response to tumor necrosis factor-alpha (TNF-alpha), and the latter activates the MMP-9 gene through NF-kappaB. Understanding the molecular basis for MMP-9 inhibition may provide tools to control cell invasion. The data reported here show the critical role of interferon regulatory factor-1 (IRF1) in the inhibition of MMP-9. (i) IFN treatment suppresses TNF-alpha-induced MMP-9 reporter activity in STAT1(+/+) cells but not in STAT1(-/-) cells. (ii) IRF1 transfection blocks TNF-alpha-mediated MMP-9 activation. (iii) IFNs phosphorylate STAT1 and induce IRF1 but do not affect Ikappa-B degradation nor NF-kappaB nuclear translocation. (iv) Nuclear NF-kappaB (p50/p65) and IRF1, but not STAT1, bind to the MMP-9 promoter region containing an IFN-responsive-like element overlapping the NF-kappaB-binding site. (v) Recombinant IRF1, although unable to bind to an NF-kappaB consensus sequence, competes with NF-kappaB proteins for binding to the MMP-9 promoter. (vi) Conversely recombinant p50/p65 proteins reduce IRF1-DNA binding. (vii) In cells cotransfected with IRF1 and/or p65 expression vectors, an excess of IRF1 reduces MMP-9 reporter activity, whereas an excess of p65 blocks the inhibitory effect of IFN-gamma. Thus, in contrast to the known synergism between IRF1 and NF-kappaB, our data identify a novel role for IRF1 as a competitive inhibitor of NF-kappaB binding to the particular MMP-9 promoter context.
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- 2002
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16. gamma-Glutamyl transpeptidase expression in Ewing's sarcoma cells: up-regulation by interferons.
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Bouman L, Sancéau J, Rouillard D, and Bauvois B
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- Bone Neoplasms genetics, Cell Division drug effects, Gene Expression Regulation, Neoplastic drug effects, Genes, p53, Humans, Interferon alpha-2, Mutagenesis, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sarcoma, Ewing genetics, Tumor Cells, Cultured, Bone Neoplasms enzymology, Gene Expression Regulation, Enzymologic drug effects, Gene Expression Regulation, Neoplastic physiology, Interferon Type I pharmacology, Interferon-alpha pharmacology, Sarcoma, Ewing enzymology, gamma-Glutamyltransferase genetics
- Abstract
The genetic hallmark of Ewing's sarcoma family of tumours (ET) is the presence of the translocation t(11;22)(q24;q12), which creates the ET fusion gene, leading to cellular transformation. Five human gamma-glutamyl transpeptidase (gamma-GT) genes are located near the chromosomal translocation in ET. gamma-GT is a major enzyme involved in glutathione homoeostasis. Five human cell lines representative of primary or metastatic tumours were investigated to study whether gamma-GT alterations could occur at the chromosomal breaks and rearrangements in ET. As shown by enzymic assays and FACS analyses, all ET cell lines consistently expressed a functional gamma-GT which however did not discriminate steps of ET progression. As shown previously [Sancéau, Hiscott, Delattre and Wietzerbin (2000) Oncogene 19, 3372-3383], ET cells respond to the antiproliferative effects of interferons (IFNs) type I (alpha and beta) and to a much less degree to IFN type II (gamma). IFN-alpha and -beta arrested cells in the S-phase of the cell cycle. We found an enhancement of gamma-GT mRNA species with IFN-alpha and -beta by reverse transcriptase-PCR analyses. This is reflected by up-regulation of gamma-GT protein, which coincides with the increase in gamma-GT-specific enzymic activity. Similarly, IFNs up-regulate the levels of gamma-GT in another IFN-responsive B cell line. Whether this up-regulation of gamma-GT by IFNs is of physiological relevance to cell behaviour remains to be studied.
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- 2002
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17. Trypanocidal drug benznidazole impairs lipopolysaccharide induction of macrophage nitric oxide synthase gene transcription through inhibition of NF-kappaB activation.
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Piaggio E, Sancéau J, Revelli S, Bottasso O, Wietzerbin J, and Serra E
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- Animals, Blotting, Western, Cells, Cultured drug effects, Cells, Cultured enzymology, Depression, Chemical, Enzyme Induction drug effects, Genes, Reporter, I-kappa B Proteins metabolism, Interferon-gamma pharmacology, Isoenzymes genetics, Macrophages enzymology, Mice, NF-kappa B metabolism, Nitric Oxide Synthase genetics, Nitric Oxide Synthase Type II, Nitrites metabolism, Phosphorylation, Protein Processing, Post-Translational, Recombinant Fusion Proteins biosynthesis, Transfection, Ubiquitin metabolism, Isoenzymes biosynthesis, Lipopolysaccharides pharmacology, Macrophages drug effects, NF-kappa B antagonists & inhibitors, Nitric Oxide Synthase biosynthesis, Nitroimidazoles pharmacology, Transcription, Genetic drug effects, Trypanocidal Agents pharmacology
- Abstract
In murine macrophages, inducible NO synthase II (NOSII) gene expression is promoted at a transcriptional level by LPS and/or IFN-gamma with benznidazole (BZL), a trypanocidal drug, acting to down-regulate NOSII gene induction and hence inhibiting NO production. By performing transient transfection experiments, we now report that BZL also inhibited the expression of NOSII gene promoter or multimerized NF-kappaB binding site controlled reporter genes. By contrast, no effect was observed on the expression of a reporter gene under the control of the NOSII promoter-derived IFN regulatory factor element. EMSAs demonstrated that BZL inhibited the nuclear availability of NF-kappaB in stimulated macrophages. NF-kappaB is activated in macrophages by phosphorylation, ubiquitination, and subsequent proteolysis of IkappaB. Within this setting, Western blot was also performed to show that BZL blocked IkappaBalpha degradation. Collectively, these results demonstrate that BZL is able to specifically inhibit macrophage NF-kappaB activation after LPS plus IFN-gamma stimulation.
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- 2001
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18. IFN-beta induces serine phosphorylation of Stat-1 in Ewing's sarcoma cells and mediates apoptosis via induction of IRF-1 and activation of caspase-7.
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Sancéau J, Hiscott J, Delattre O, and Wietzerbin J
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- 2',5'-Oligoadenylate Synthetase genetics, Caspase 7, Cell Division drug effects, DNA-Binding Proteins genetics, Enzyme Activation, Gene Expression drug effects, Humans, Interferon Regulatory Factor-1, Interferon alpha-2, Interferon beta-1a, Interferon-Stimulated Gene Factor 3, Interferon-Stimulated Gene Factor 3, gamma Subunit, Interferon-alpha metabolism, Interferon-alpha pharmacology, Interferon-beta pharmacology, Janus Kinase 1, Mitogen-Activated Protein Kinases metabolism, Phosphoproteins genetics, Phosphorylation, Promoter Regions, Genetic, Protein-Tyrosine Kinases metabolism, Proteins metabolism, Recombinant Proteins, STAT1 Transcription Factor, Sarcoma, Ewing, Signal Transduction, TYK2 Kinase, Transcription Factors metabolism, Tumor Cells, Cultured, p38 Mitogen-Activated Protein Kinases, Apoptosis, Caspases metabolism, DNA-Binding Proteins biosynthesis, DNA-Binding Proteins metabolism, Interferon-beta metabolism, Phosphoproteins biosynthesis, Serine metabolism, Trans-Activators metabolism
- Abstract
Four human cell lines derived from Ewing's sarcoma, EW-7, EW-1, COH and ORS, were investigated to establish the effects of human recombinant interferon-alpha2a and human recombinant interferon-beta on cell proliferation and apoptosis. All four cell lines were much more sensitive to the antiproliferative effects of IFN-beta than of IFN-alpha. Analysis of the early signals triggered by IFN-alpha and IFN-beta demonstrated that the two IFNs were similarly effective in inducing tyrosine phosphorylation of the Jak-1 and Tyk-2 kinases and the transcription factors Stat-1 and Stat-2. Interestingly, an additional rapid phosphorylation of Stat-1 on serine was observed after IFN-beta treatment, with concomitant activation of p38 mitogen-activated protein kinase. In these cells, Stat-1 Ser727 phosphorylation in response to IFN-beta was found to be impaired by p38 MAPkinase inhibitor (SB203580). IFN-beta induced the formation of the Interferon Stimulated Gene Factor 3 complex more efficiently than IFN-alpha, as well as sustained induction of IRF-1, which may account for its greater induction of 2'5'oligo(A)synthetase and greater inhibition of cell proliferation. IFN-beta, but not IFN-alpha, induced apoptosis in wild-type p53 EW-7 and COH cell lines, but not in the mutated p53 EW-1 or ORS cell lines. The apoptosis induced by IFN-beta in EW-7 and COH cell lines appeared to be mediated by IRF-1 and involved the activation of caspase-7. Ectopic expression of IRF-1 induced apoptosis in all four cell lines which correlated with the activation of caspase-7 and with the downregulation of the Bcl-2 oncoprotein, as observed for IFN-beta-induced apoptosis in parental EW-7 and COH cell lines.
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- 2000
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19. Production of nitric oxide (NO) in human hydatidosis: relationship between nitrite production and interferon-gamma levels.
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Touil-Boukoffa C, Bauvois B, Sancéau J, Hamrioui B, and Wietzerbin J
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- Adult, Animals, Antigens, Helminth immunology, Female, Humans, Interleukin-6 blood, Leukocytes, Mononuclear, Male, Tumor Necrosis Factor-alpha analysis, Echinococcosis metabolism, Interferon-gamma biosynthesis, Nitric Oxide metabolism, Nitrites metabolism
- Abstract
Human hydatidosis is characterized by a prolonged coexistence of parasite (Echinococcus granulosus) and host without effective rejection. The basis of the immune response of the patient is poorly understood. Previously, we reported the presence of IFN, TNF-alpha and IL-6 activities in the serum of patients with liver and lung hydatidosis. In the present work, we have investigated the production of nitrite (NO2-) in the serum of hydatidic patients carrying hepatic and pulmonary cysts (range 36-300 microM). Our present data show a correlation between the production of nitrite + nitrate (NO2- + NO3-) and that of circulating cytokines IFN and IL-6. In relapsing patients who did not produce IFN and IL-6, the observed serum NO2- concentrations were low (range 10-37.2 microM), as compared to those detected in patients before surgery. Induction of NO synthase in leukocytes from hydatidic patients was induced by stimulating these cells with a specific parasitic antigen, Antigen-5, as assessed by the increased levels of NO3- + NO2- in the range of 60-85 microM for patients with liver hydatidosis, as compared to the 20-25 microM detected in healthy controls. Collectively, our data indicate that NO2- + NO3- levels correlate with IFN levels and immunoreactivity, and overall suggest that IFN-gamma and nitric oxide production together play a role in the host defense mechanisms in human hydatidosis.
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- 1998
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20. Relationship among circulating interferon, tumor necrosis factor-alpha, and interleukin-6 and serologic reaction against parasitic antigen in human hydatidosis.
- Author
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Touil-Boukoffa C, Sancéau J, Tayebi B, and Wietzerbin J
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- Antigen-Antibody Reactions, Antigens, Helminth blood, Cell Line, Echinococcosis immunology, Echinococcosis surgery, Echinococcosis, Hepatic blood, Echinococcosis, Hepatic surgery, Humans, Interferons blood, Interleukin-6 blood, Serology, Tumor Necrosis Factor-alpha metabolism, Antigens, Helminth immunology, Echinococcosis blood, Interferons immunology, Interleukin-6 immunology, Tumor Necrosis Factor-alpha immunology
- Abstract
Human hydatidosis is a parasitic disease vectored by the larval stage cestode Echinoccocus granulosus. It constitutes a major health problem in North Africa. We investigated the production of circulating interferon (IFN), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in Algerian patients with liver, lung, or ocular hydatidosis. In all, 101 serum samples from these patients with analyzed. Immunoreactivity and cytokine activities were undetectable in sera from ocular hydatidosis patients. However, we observed the presence of IFN (a mixture of IFN-alpha, IFN-beta, and IFN-gamma, range 32-500 U/ml), TNF-alpha (range 32-100 U/ml), and IL-6 (range 32-500 U/ml) in all patients who had liver or lung cysts or both and displayed immunoreactivity against parasitic antigen (antigen 5). After surgical removal of the cysts, serum cytokine levels declined rapidly and were undetectable at 30 days. IFN and IL-6 activity was undetectable in sera from two liver hydatidosis patients who relapsed and did not display any immune response against parasitic antigen. These results suggest that in liver and lung hydatidosis, cytokine production contributes to the host defense mechanism against the extracellular parasite.
- Published
- 1997
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21. Inactivation of interleukin-6 in vitro by monoblastic U937 cell plasma membranes involves both protease and peptidyl-transferase activities.
- Author
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Laouar A, Villiers C, Sancéau J, Maison C, Colomb M, Wietzerbin J, and Bauvois B
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- Cells, Cultured, Humans, Hydrolysis, Interleukin-6 metabolism, Iodine Radioisotopes, Kinetics, Recombinant Proteins antagonists & inhibitors, Recombinant Proteins metabolism, Aminopeptidases physiology, Cell Membrane enzymology, Interleukin-6 antagonists & inhibitors, Serine Endopeptidases physiology
- Abstract
Human promonocytic U937 cells have previously been shown to possess at their cell surface specific transmembrane serine proteases and N-terminal amino acid proteases as well as associated enzymes including elastase and cathepsin G. In this study, purified plasma membranes from U937 cells are reported to degrade the recombinant 21-kDa 125I-interleukin-6 (125I-IL-6) into 8-kDa products with loss of biological activity, as monitored by polyacrylamide gel electrophoresis and a cell-proliferation bioassay. Degradation of 125I-IL-6 by plasma membranes was completely prevented by the serine-protease inhibitor diisopropyl fluorophosphate, but was only partially impaired by alpha 1-protease inhibitor and antibody against cathepsin G. A similar incubation of 125I-IL-6 with cathepsin G purified from U937 cells caused hydrolysis of the cytokine into similar inactive 8-kDa fragments, whereas incubation with purified U937 cell elastase failed to degrade the peptide. These findings indicate that U937 cells hydrolyze IL-6 using cell-associated serine-protease activity and that cathepsin G partially participates in this degradation. Prolonged incubation of 8-kDa 125I-IL-6 fragments with purified U937 plasma membranes, led to a complete loss of IL-6 activity related to the transformation of the 8-kDa forms into a higher-molecular-mass complex (16 kDa). This complex was stable in SDS and 2-mercaptoethanol at 100 degrees C and was not dissociated by hydroxylamine treatment, indicating the formation of a covalent non-ester bond between the 8-kDa 125I-IL-6-derived peptide and an undetermined acceptor. An initial oxidative treatment of 125I-IL-6 partially prevented complex formation, suggesting the presence of one or more oxidizable methionine residues at the binding site of 8-kDa 125I-IL-6 peptide. The kinetics of complex formation (time dependence and plasma-membrane-concentration dependence), as well as its inhibition by a specific inhibitor of N-amino-peptidase activity, bestatin, suggest the participation of peptidyl-transferase activity in complex formation. Finally, a plasma-membrane fraction, corresponding to a molecular mass > or = 30 kDa, was able to convert the 8-kDa 125I-IL-6 forms into the 125I-labeled 16-kDa complex, suggesting that a > or = 30-kDa peptidyl-transferase enzyme catalyzes the reaction and provides the 125I-labeled 16-kDa peptide by dimerization of 8-kDa 125I-IL-6-derived intermediates. Further identification of the plasma-membrane-associated peptidyl transferase as a regulator of IL-6 proteolysis may be of physiological relevance for the control of IL-6 biological activity.
- Published
- 1993
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22. Interferon-gamma modulates retinoblastoma gene mRNA in monocytoid cells.
- Author
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Mistchenko AS, Diez RA, Romquin N, Sancéau J, and Wietzerbin J
- Subjects
- Actins metabolism, Blotting, Northern, Cell Line, Cycloheximide pharmacology, Drug Interactions, Humans, Time Factors, Interferon-gamma pharmacology, Monocytes metabolism, RNA, Messenger metabolism, Retinoblastoma Protein metabolism
- Abstract
To study the effect of interferon gamma (IFN-gamma) on the expression of the retinoblastoma (RB) susceptibility gene, we performed Northern-blot analysis on RNA extracted from Wish, HEL and monocytoid cell lines U-937 and THP-1 treated with 1,000 IU/ml of recombinant IFN-gamma. In U-937 and THP-1 cells, IFN-gamma increased the abundance of RB mRNA. In Wish and HEL cells, co-treatment with cycloheximide was required for IFN-gamma to increase the level of RB mRNA. Pre-treatment of THP-1 cells with cycloheximide prior to IFN-gamma treatment augmented the effects of IFN-gamma on RB gene expression. The effect of IFN-gamma in THP-1 cells was observed after 3 hr of treatment, being more pronounced after 6 hr and persisting until at least 18 hr, although at a lower level. These results suggest that IFN-gamma regulates the level of RB mRNA by different mechanisms in the different cell types. This cytokine increases the abundance of RB mRNA in monocytoid cell lines, reinforced by prior treatment with cycloheximide. Inhibition of protein synthesis is required in Wish and HEL cell lines before IFN-gamma has an effect on RB gene expression.
- Published
- 1993
- Full Text
- View/download PDF
23. Human U937 cell surface peptidase activities: characterization and degradative effect on tumor necrosis factor-alpha.
- Author
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Bauvois B, Sancéau J, and Wietzerbin J
- Subjects
- Amino Acid Sequence, Cell Membrane enzymology, Cytokines metabolism, Dipeptidyl Peptidase 4, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases metabolism, Humans, In Vitro Techniques, Macrophages enzymology, Molecular Sequence Data, Peptides chemistry, Peptides metabolism, Protease Inhibitors pharmacology, Substrate Specificity, Tumor Cells, Cultured, Monocytes enzymology, Peptide Hydrolases metabolism, Tumor Necrosis Factor-alpha metabolism
- Abstract
Surface peptidase activities on the human monocytic lineage cell line U937 were characterized. Two diisopropyl phosphofluoridate (DFP)-inhibitable serine peptidases were identified by differences in their hydrolytic activities on chromogenic peptides: one removed tripeptides from the free NH2-terminal end of the synthetic peptide Ala-Ala-Phe-p-nitroanilide (pNA) and was not inhibited by inhibitors of metallo-, cysteic-, and aspartic-proteinases, or by those of elastase-, trypsin- and chymotrypsin-like enzymes, suggesting the presence of a hitherto unidentified serine tripeptidyl endopeptidase; the other peptidase catalyzed the release of Gly-Pro from Gly-Pro-pNA and was inhibited by DFP, phenylmethyl sulfonyl fluoride and diprotin A, thus resembling dipeptidyl peptidase IV (DPP IV) with respect to its substrate specificity and inhibitor profile. A group of N-exo-aminopeptidase activities specifically inhibited by bestatin, was also detected when Ala-, Leu-, Arg- and Lys-pNA were used a substrates. The activities were surface associated and not secreted as determined by extracellular location of product and enzymatic recovery in highly purified U937 cell membranes. Peripheral monocytes and macrophages were found to virtually exhibit identical levels of these two classes of peptidase activities when compared to those detected on U937 cells. The relative contributions of these hydrolytic enzymes to the cleavage of bioactive and radioiodinated cytokines including tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha and interferon-gamma was next examined. The results indicated that N-aminopeptidases do not appear to participate in the catabolism of any tested cytokine. In contrast, the most interesting finding was that both serine peptidases participate in TNF-alpha degradation. Analysis of the final proteolytic digestion products demonstrated the disappearance of the native 17-kDa molecule TNF-alpha, and the concomitant release of biologically inactive fragments of less than or equal to 2 kDa. Together, these observations indicate new roles for both the DPP IV-like enzyme and the tripeptidyl endopeptidase located at the surface of human monocytic cells, including the regulation of the extracellular TNF-alpha concentration. Thus, the identification of functional ectopeptidases provides insight into their potential role in both normal and malignant monocytic function.
- Published
- 1992
- Full Text
- View/download PDF
24. Helper activity for antibody synthesis encoded by mRNA extracted from human peripheral blood mononuclear cells.
- Author
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Sénik A, Vaquero C, Kolb JP, Galhina A, Provost MA, Sancéau J, Catinot L, and Falcoff R
- Subjects
- Animals, Antibody Formation, Female, Humans, Interleukin-2 biosynthesis, Lymphoma immunology, Mice, Mice, Inbred Strains, Mice, Nude, Oocytes metabolism, Poly A genetics, RNA genetics, T-Lymphocytes immunology, Xenopus, Antibodies genetics, RNA, Messenger genetics, T-Lymphocytes, Helper-Inducer immunology
- Abstract
Translation products in Xenopus laevis of mRNA from human peripheral blood mononuclear cells were tested for their capacity to replace T cells in the anti-SRBC response of nude spleen cells. When the starting material came from PHA or FCS-stimulated lymphocytes, the translated lymphokines, displaying such a B cell helper activity were found to be encoded by mRNA sedimenting at 6-7S and 13S on a sucrose density gradient. 6-7S mRNA from control, non-stimulated lymphocytes was also able to code for B cell helper activity. Thorough T-cell depletion of mouse responder cell populations left unchanged the activity of 6-7S mRNA products while preventing that of 13S products. The latter were found to contain IL-2, which suggests that their action on B cells was indirect, mediated by T-cell stimulation.
- Published
- 1984
- Full Text
- View/download PDF
25. Expression of extracellular and intracellular human IFN-gamma in mouse L cells transformed with the human IFN-gamma cDNA gene.
- Author
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Sancéau J, Lewis JA, Sondermeyer P, Beranger F, Falcoff R, and Vaquero C
- Subjects
- 2',5'-Oligoadenylate Synthetase metabolism, Animals, Cell Compartmentation, Cells, Cultured, Cytoplasm metabolism, Epitopes, Extracellular Space metabolism, Humans, Interferon-gamma immunology, Interferon-gamma metabolism, Mice, Protein Kinases metabolism, Recombinant Proteins immunology, Recombinant Proteins metabolism, Thymidine Kinase genetics, Transfection, Viral Interference, Interferon-gamma genetics, Recombinant Proteins genetics
- Abstract
Cotransformation with a plasmid containing a thymidine kinase gene (pTK2) and a plasmid encoding human IFN-gamma (pTG11) has been used to establish murine L cell lines expressing human IFN-gamma. The HuIFN-gamma gene was present in 30% of the tk+ cell lines and some of these secreted low levels of IFN into the culture medium. Two of the clones obtained after transformation were selected for detailed analysis. Clone 1-12 constitutively secreted very low levels of HuIFN-gamma in the culture medium. This antiviral activity was characterized by its species specificity and antigenicity as authentic human IFN-gamma In contrast, clone 3-47 produced a HuIFN-gamma activity which could only be detected intracellularly. This clone was resistant to infection both by Vesicular stomatitis (VSV) and Mengo viruses and contained increased levels of enzymes known to be induced by interferon. Our results suggest that clone 3-47 produces a non-secreted HuIFN-gamma like molecule which is able to trigger an antiviral state in the murine cell independent of the interaction with a specific IFN-gamma surface receptor.
- Published
- 1986
- Full Text
- View/download PDF
26. Interferon-beta 2 (BSF-2) mRNA is expressed in human monocytes.
- Author
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Sancéau J, Falcoff R, Zilberstein A, Béranger F, Lebeau J, Revel M, and Vaquero C
- Subjects
- Cell Adhesion, Humans, Interferon Type I analysis, Neutralization Tests, Precipitin Tests, Protein Biosynthesis, Gene Expression Regulation, Interferon Type I genetics, Monocytes analysis, RNA, Messenger genetics
- Abstract
We previously have reported the presence of interferon-beta 2 (IFN-beta 2) mRNA in PHA-stimulated human peripheral blood leukocytes (PBL), as well as in nonstimulated cells, although at a lower level. The IFN-beta 2 cloned from a leukocyte library appeared to be similar to that of the fibroblast IFN-beta 2 gene first described in fibroblasts. To assess the nature of the cell population in which the synthesis of IFN-beta 2 takes place, PBL were fractionated in adherent and nonadherent cells. The antiviral activity of the culture supernatants of adherent cells was characterized as the IFN-beta type by neutralization with polyclonal antibodies raised against purified fibroblast IFN-beta 2. IFN-beta 2 mRNA was observed in enriched monocyte populations and accumulated very rapidly, peaking at 2.5 h. RNA extracted from these cultures encoded in a reticulocyte lysate a protein immunoprecipitated by the anti-IFN-beta 2 antiserum. In addition, IFN-beta 2 secreted in monocyte supernatants also was immunoprecipitated by the specific antiserum and was able to compete with the fibroblast IFN-beta 2, suggesting a strong similarity between the fibroblast and monocyte proteins.
- Published
- 1988
- Full Text
- View/download PDF
27. Protein synthesis in extracts from interferon-treated Mengo virus infected cells.
- Author
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Vaquero C, Sancéau J, and Falcoff R
- Subjects
- Animals, Kinetics, L Cells drug effects, L Cells metabolism, Mice, Polyribosomes drug effects, Polyribosomes metabolism, Ribonucleases metabolism, Cell Transformation, Viral drug effects, Interferons pharmacology, Mengovirus genetics, Protein Biosynthesis drug effects
- Published
- 1982
- Full Text
- View/download PDF
28. Translation of mRNA from phytohemagglutinin-stimulated human lymphocytes: characterization of interferon mRNAs.
- Author
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Vaquero C, Sancéau J, Catinot L, Andreu G, Falcoff E, and Falcoff R
- Subjects
- Animals, Female, Humans, In Vitro Techniques, Interferon-gamma immunology, Molecular Weight, Oocytes metabolism, Phytohemagglutinins pharmacology, Poly A metabolism, Xenopus laevis, Interferon-gamma biosynthesis, Lymphocyte Activation, Protein Biosynthesis, RNA, Messenger metabolism
- Abstract
Human lymphocytes obtained by cytapheresis were stimulated in spinner culture conditions by nonpurified PHA in order to study the production of gamma interferon, and the characterization of IFN-gamma mRNA. Titers of interferon prepared in 0.6 to 4 1 batches, varied in 20 preparations from 8,000 to 32,000 units/ml. This interferon was unstable at pH 2: the residual antiviral activity after 20 h treatment was less than 3%. Antibodies raised against gamma interferon from Con A and SEA-stimulated lymphocytes neutralized the interferon induced by PHA, indicating that all three preparations are antigenically related. Poly(A)RNA from control, noncultivated lymphocytes and from lymphocytes stimulated by PHA for 18 h were translated in reticulocyte lysates and analysed by polyacrylamide gel electrophoresis. The pattern of synthesized polypeptides was different suggesting modifications in the population of mRNA. When total poly(A)RNA was inoculated into Xenopus Laevis oocytes, interferon activity was found with both, control and stimulated mRNAs although only at low levels in the control. After sucrose gradient fractionation of poly(A)RNA, each fraction was inoculated into oocytes and interferon activity measured in the oocyte bathing medium. A low level was synthesized by the RNA fractions around 28 S from control as well as from stimulated lymphocytes. These interferons were not neutralized by anti-IFN-alpha or anti-IFN-gamma sera but they were neutralized by anti-IFN-beta serum. Only the 16 S RNA fraction from PHA-stimulated lymphocytes induced high levels of interferon in oocytes. This interferon has been characterized as gamma interferon. Each fraction obtained from sucrose gradients on poly(A)RNA from control and PHA-stimulated lymphocytes was translated in reticulocyte lysate. Gel analysis of the products showed striking differences when the same fraction of both RNAs were compared. Concerning particularly the 16 S RNA from PHA-stimulated lymphocytes, where gamma interferon mRNA was present, polypeptides ranged from 15 to 55 K with a bulk around 45 K, indicating heterogeneous RNA molecules.
- Published
- 1982
- Full Text
- View/download PDF
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