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Mechanism of Interferon Action: Inhibition of Viral Messenger Ribonucleic Acid Translation in L-Cell Extracts

Friedman, R. M.; Metz, D. H.; Esteban, R. M.; Tovell, D. R.; Ball, L. A.; Kerr, I. M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1972 Português
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Encephalomyocarditis (EMC) virus ribonucleic acid (RNA) stimulated the incorporation of 14C-amino acids into polypeptides in cell-free systems using preincubated S10 extracts from L cells. Incorporation was linear for over 2 hr. Analysis of the tryptic peptides derived from the polypeptide products formed in response to EMC RNA showed them to be virus specific. The major product, a polypeptide of 140,000 in molecular weight, migrated on sodium dodecyl sulfate-polyacrylamide gels with one of the virus-specific polypeptides present in EMC-infected cells. A minor component of molecular weight about 230,000 may correspond to the product of complete translation of the EMC virus genome. Little or no effect of interferon or vaccinia virus infection was observed in the preincubated, cell-free system. The EMC RNA-stimulated incorporation of 14C-amino acids into polypeptides was not inhibited in extracts derived from L cells early in virus infection, from interferon-treated cells, or from cells subjected to both treatments. Interferon treatment did appear to have a slight inhibitory effect on chain elongation in this system. However, treatment of cells with highly purified interferon before virus infection caused a decrease of about 80% in the capacity of non-preincubated cell extracts to translate added EMC RNA. This effect did not extend to the translation of polyuridylic acid and could be reversed by preincubation of the extracts at 37 C for 20 min. The inhibition of translation was manifest at interferon concentrations as low as 5IU/ml...

Interferon Production by Human Leukocytes In Vitro: Some Biological Characteristics1

Lee, Spencer H. S.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1969 Português
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Interferon was optimally produced in human peripheral leukocyte cultures incubated for approximately 19 hr in the presence of Sendai virus at a multiplicity of 10 to 50 EID50/cell. For determining whether deoxyribonucleic acid (DNA) synthesis per se was essential for interferon production, 1-β-D-arabinofuranosylcytosine (Ara-C), a potent DNA inhibitor was studied for its effect on interferon production in leukocytic and bone marrow cell cultures. These cells showed no impaired capacity to produce interferon when treated with 15 μg of Ara-C per ml. Interferon yields were also determined in leukocyte cultures treated with actinomycin D (0.1 μg/ml) and puromycin (10 μg/ml) at various times before and after virus inoculation. The data suggested that sequential transcriptive and translational events were required for the de novo synthesis of interferon by the infected leukocytes, in a manner similar to other known virus-induced interferon-producing systems. The synthesis of macromolecules and the effects of antimetabolites in leukocytes and bone marrow cell cultures were followed by measuring the incorporation of thymidine-2-14C, uridine-5-3H, and L-phenylalanine-1-14C. The effect of 0.1 μg of actinomycin per ml on the capacity of leukemic leukocytes to produce interferon was also studied. Preliminary data showed that...

Mechanism of interferon action: Phosphorylation of protein synthesis initiation factor eIF-2 in interferon-treated human cells by a ribosome-associated kinase processing site specificity similar to hemin-regulated rabbit reticulocyte kinase

Samuel, Charles E.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1979 Português
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The phosphorylation of purified protein synthesis factors catalyzed by protein kinase preparations isolated from interferon-treated human amnion cells was examined. Ribosomal salt-wash fractions prepared from interferon-treated human cells contained a protein kinase that catalyzed the [γ-32P]ATP-mediated phosphorylation of the 38,000-dalton subunit of eukaryotic initiation factor 2 (eIF-2α); this kinase activity was significantly enhanced in interferon-treated as compared to untreated cells. The tryptic [32P]phosphopeptide pattern obtained for eIF-2α phosphorylated by the interferon-mediated human kinase was indistinguishable from the pattern obtained for eIF-2α phosphorylated by the hemin-regulated rabbit reticulocyte kinase when analyzed by thin-layer chromatography with three different solvent systems and by high-voltage electrophoresis. O-[32P]Phosphoserine was liberated by partial acid hydrolysis from eIF-2α phosphorylated by either the human or the rabbit kinase. In addition to the phosphorylation of eIF-2α, interferon treatment of human cells enhanced the phosphorylation of two additional ribosome-associated proteins designated P1 and Pf. The major phosphoester linkage observed for the human, as well as murine, phosphoprotein P1 was O-phosphoserine. The interferon-mediated phosphorylation of both eIF-2α and protein P1 was dependent upon the presence of RNA with double-stranded character; Pf phosphorylation was not affected by double-stranded RNA. These results suggest that the interferon-mediated ribosome-associated human protein kinase catalyzes the phosphorylation of eIF-2α in a site-specific manner that is apparently identical with the reaction catalyzed by the hemin-regulated rabbit reticulocyte kinase; hence...

Mechanism of calcium ionophore A23187-induced priming of bone marrow-derived macrophages for tumor cell killing: relationship to priming by interferon.

Johnson, H M; Torres, B A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1985 Português
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Interferon primes macrophages for tumor cell killing by rendering them sensitive to triggering agents such as lipopolysaccharide. In an attempt to determine the nature of the priming signal, we tested phorbol 12-myristate 13-acetate, diacylglycerol, platelet-activating factor, arachidonic acid, leukotriene B4, and the calcium ionophore A23187 for their ability to prime mouse bone marrow-derived macrophages for activation to kill P815 mastocytoma target cells. The ionophore A23187 was the only substance that was able to replace the interferon priming signal. A23187 priming appeared to be due in part to induction of interferon alpha/beta in the macrophage cultures, since its effect was partially but specifically blocked by antibody to interferon alpha/beta. Consistent with this was the observation that A23187 induced interferon alpha/beta production in macrophage cultures. The fact that A23187 priming was not completely reversed by antibody to interferon would suggest that factors unrelated to interferon induction also played a role in macrophage priming. The failure of phorbol myristate acetate or diacylglycerol to prime macrophages for tumor cell killing would suggest that activation of protein kinase C is not sufficient for priming. Thus...

Immune interferon production by lymphoid cells: role in the inhibition of herpesviruses.

Babiuk, L A; Rouse, B T
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1976 Português
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Bovine peripheral blood lymphocytes (PBL) obtained from infectious bovine rhinotracheitis (IBR) virus- and tuberculin-immunized animals produced large quantities of interferon within 24 h of in vitro stimulation by IBR and purified protein derivative antigens. Separation of PBL into populations enriched in T lymphocytes or B lymphocyte provided the antigen-specific step for immune interferon production. A 2- to 10-fold increase in interferon occurred when lymphocytes were combined with autologous macrophages. Although macrophages, even if treated with antilymphocyte serum to remove any contaminating lymphocytes, could produce some interferon, the augmented interferon produced by macrophage-lypmhocyte cultures was not dmpocytes. Direct physical contact between macrophages and lymphocytes was required for the production of enhanced levels of interferon. Antigen-antibody complexes of irradiated virus-infected cells in the presence of antibody were as efficient or better at stimulating interferon than was free antigen. Because IBR virus was inhibited by interferon levels stimulated in cultures by IBR antigen, it was suggested that the local production of interferon by immune cells might play a similar role in curtailing virus dissemination in vivo...

In Vivo Release of Previously Cleared Interferon by Cycloheximide

Chester, Thomas J.; De Clercq, Erik; Nuwer, Marc R.; Merigan, Thomas C.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1972 Português
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The release of previously cleared interferon by cycloheximide was studied in the mouse. When cycloheximide was administered after either endogenous interferon stimulation or administration of exogenous interferon, the clearance of interferon from the blood stream was interrupted and a sharp rise in interferon titer occurred approximately 6 hr after cycloheximide administration followed by a rapid decline to low levels. This effect was observed with either interferon stimulated endogenously (by polyriboinosinic·polyribocytidylic acid), or homologous (mouse) or heterologous (rabbit) interferon administered exogenously. Serum protein concentrations also exhibited this rise and fall phenomenon after cycloheximide administration although the magnitude of the change in protein concentrations was less pronounced than that observed with interferon. Hematocrits, although elevated in mice receiving cycloheximide, did not exhibit this rise and fall phenomenon. Hence, cycloheximide administration leads to the release into the circulation of previously cleared interferon as well as other proteins.

Induction of Interferon in L Cells by Reoviruses

Gauntt, C. J.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1973 Português
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L cell cultures challenged with reoviruses types 1 and 3 produced little to no detectable interferon under conditions which permitted virus replication and under conditions which prevented replication of a temperature-sensitive mutant strain of reovirus type 3 (ts-1). Ultraviolet-irradiated reoviruses and double-stranded ribonucleic acids extracted from purified reovirus type 3 also induced little to no interferon in L cell cultures. Under similar conditions, MM virus proved to be an effective inducer of interferon. Exposure of L cells to interferon prior to challenge with virus (priming) failed to enhance interferon production upon subsequent challenge with reovirus although priming increased the amount of interferon produced following MM virus challenge. L cell cultures that were challenged with reovirus type 3 and subsequently with either MM or Colorado tick fever viruses produced similar titers of interferon as cell cultures that were challenged with either MM or Colorado tick fever virus alone, respectively. These data show that the presence of production of reovirus type 3 double-stranded ribonucleic acid is not sufficient for induction of interferon in L cell cultures and that additional processes which are required for induction of interferon in L cell cultures are not expressed by reovirus type 3.

Influences of gamma interferon on synovial fibroblast-like cells. Ia induction and inhibition of collagen synthesis.

Amento, E P; Bhan, A K; McCullagh, K G; Krane, S M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1985 Português
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The shape and function of adherent cells cultured from rheumatoid synovial membranes are influenced by immune cells, and their products. The synovial cells produce collagenase and prostaglandin E2 (PGE2), the levels of which are increased when the cells are incubated with the monokine, mononuclear cell factor/interleukin 1. The majority of adherent synovial cells are fibroblastlike in appearance and synthesize collagens and fibronectin; the synthesis of collagens and fibronectins are also increased by a monocyte factor. In the present study we found that the fibroblastlike cells expressed major histocompatibility complex class II (Ia-like) antigens after initial dispersion from the synovial membrane. Monocyte lineage antigens were detected on some round cells in early passage, but no T lymphocytes were identified in established cultures. There was loss of Ia expression on the fibroblastlike cells with age and passage in culture. The addition of the lymphokine, gamma interferon (recombinant), induced class II antigen (DR and DS/DQ) expression in early or late passage cells in a time- and dose-dependent manner and required protein synthesis. Furthermore, the adherent synovial fibroblastlike cells continued to be Ia-positive when examined as long as 10 d after the removal of gamma interferon. Ia expression was also induced by gamma interferon in normal skin fibroblasts. Synovial cells that could be induced to express Ia also bound a monoclonal antibody to type III collagen (a fibroblast marker). Gamma interferon...

Enucleation and reconstruction of interferon-producing cells.

Burke, D C; Veomett, G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1977 Português
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Enucleation of L cells leads to loss of the capacity to produce interferon, showing that the cell nucleus is essential for interferon formation. However, when the cells were enucleated while interferon formation. However, when the cells were enucleated while interferon formation was proceeding, the cytoplasts were capable of continuing to synthesize interferon by a process shown to be protein synthesis, showing that the interferon messenger RNA leaves the nucleus after synthesis. Reconstructed cells were obtained by Sendai virus fusion of karyoplasts and cytoplasts. Such reconstructed cells were capable of producing at least as much interferon (43 interferon units/10(4) nucleated cells) as control cells (31 interferon units/10(4) nucleated cells).

Tilorone Hydrochloride: an Oral Interferon-Inducing Agent

Stringfellow, Dale A.; Glasgow, Lowell A.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1972 Português
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Tilorone hydrochloride characteristically induces an unusually delayed and prolonged interferon response not commonly associated with other synthetic inducers. Maximum circulating interferon levels of 8,000 to 10,000 units/ml were detected 12 hr postinoculation and persisted for up to 30 hr after administration of tilorone. The fact that both oral and intraperitoneal injections of tilorone induce a similar response suggests that this delay is not based on the time required for adsorption from the gastrointestinal tract. In vitro, tilorone failed to induce detectable levels of interferon in either mouse peritoneal lymphocyte or macrophage cell cultures. Furthermore, interferon production could not be detected in the upper gastrointestinal tract after oral administration of tilorone. The striking suppression of interferon production in X-irradiated mice suggested that lymphatic tissue may be a source of interferon in response to tilorone. This concept was not supported, however, by experiments utilizing antilymphocyte serum (ALS). Tilorone induced comparable levels of interferon in both ALS-treated and control animals which had received normal serum, even though the ALS-treated mice had decreased spleen weights and peripheral lymphocyte counts. These data suggest that a radiosensitive cell population other than lymphocytes may be an important factor in the capacity of the host to produce interferon in response to tilorone. Mice which received repeated injections of tilorone developed a severe state of hyporeactivity. The degree of hyporeactivity was particularly striking when compared to that induced by polyinosinic acid:polycytidylic acid and emphasizes one of the major obstacles confronting interferon inducers as chemotherapeutic agents.

Large-Scale Production and Partial Purification of Mouse Immune Interferon

Osborne, L. C.; Georgiades, J. A.; Johnson, H. M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1979 Português
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Large-scale production of high-titered (102.2 to 104 U/ml) immune interferon (type II) was carried out in roller cultures of mouse spleen cells by using the T-cell mitogen staphylococcal enterotoxin A. Precipitation of 90% of this interferon by 55 to 80% saturated ammonium sulfate resulted in a 20-fold concentration and a two- to sixfold purification. After application of this interferon to either bovine serum albumin (BSA)-Affi-Gel 10 or hydroxylapatite columns, 100% of the interferon activity was recovered. By BSA-Affi-Gel 10 chromatography, 7% of the recovered activity was not bound, 45% was eluted with pH gradient 5 to 7, and 48% was eluted with 1 M NaCl. The pH- and salt-eluted interferons from the BSA-Affi-Gel 10 column were purified 62- and 390-fold, respectively, when compared with the starting materials. Rechromatography of the pH- and salt-eluted interferon peaks from the BSA-Affi-Gel 10 column did not alter their elution patterns. Stepwise elution of interferon from the BSA-Affi-Gel 10 columns with buffers of various pH and salt contents also resulted in greater than 300-fold purification. Specific activities of up to 2 × 105 U of interferon per mg of protein were attained with either elution procedure from BSA-Affi-Gel 10 columns. By hydroxylapatite chromatography...

Conditions required for induction of interferon by rotaviruses and for their sensitivity to its action.

McKimm-Breschkin, J L; Holmes, I H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1982 Português
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Our investigations of interferon induction by rotaviruses showed that only when cells were pretreated with interferon, i.e., primed, could infectious rotaviruses induce significant quantities of interferon. As little as 0.5 U of interferon provided sufficient priming for this induction. UV-irradiated rotaviruses induced significant levels of interferon, and priming only marginally enhanced the yields. Neither heat-inactivated virus nor serum-neutralized virus was able to induce interferon, even when cells were primed. When cells were treated with purified virus double-stranded RNA in the presence of DEAE-dextran to facilitate uptake, interferon was induced, although priming did not enhance yields. These results strongly implicate the viral double-stranded RNA as the effector for interferon induction. The insensitivity of rotaviruses to interferon in vitro was also studied. Results suggested that this lack of sensitivity was not due to any inherent resistance of the virus to the antiviral proteins, but rather to lack of activation of cellular enzymes exhibiting antiviral activity.

Interferon selectively inhibits the expression of mitochondrial genes: a novel pathway for interferon-mediated responses.

Shan, B; Vazquez, E; Lewis, J A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1990 Português
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As an approach to identifying genes involved in physiological actions of interferons we used differential probes to screen a cDNA library from mouse L-929 cells treated with interferon alpha/beta. We identified two negatively regulated mRNA species which have been examined by analysis of the corresponding mRNAs and by DNA sequencing. Comparison with the GenBank database showed that these cDNA clones corresponded to mitochondrially encoded genes for cytochrome b and subunit I of cytochrome c oxidase. A further cDNA encompassing three mitochondrial genes was used as a probe to show that a third mRNA, NADH dehydrogenase subunit 5, was also down-regulated by interferon while a fourth, NADH dehydrogenase subunit 6, was unaffected. Expression of cytochrome b was also inhibited in mouse NIH 3T3 cells treated with interferon alpha/beta and in human Daudi lymphoblastoid cells treated with interferon alpha. The ability of interferon to reduce mitochondrial mRNA levels could be blocked by cycloheximide suggesting that these effects are mediated by an interferon-responsive nuclear gene which encodes a product capable of regulating mitochondrial gene expression. Analysis of proteins synthesized in the presence of emetine, a specific inhibitor of cytoplasmic translation...

The Pathogenic NY-1 Hantavirus G1 Cytoplasmic Tail Inhibits RIG-I- and TBK-1-Directed Interferon Responses

Alff, Peter J.; Gavrilovskaya, Irina N.; Gorbunova, Elena; Endriss, Karen; Chong, YuSon; Geimonen, Erika; Sen, Nandini; Reich, Nancy C.; Mackow, Erich R.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /10/2006 Português
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Hantaviruses cause two diseases with prominent vascular permeability defects, hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome. All hantaviruses infect human endothelial cells, although it is unclear what differentiates pathogenic from nonpathogenic hantaviruses. We observed dramatic differences in interferon-specific transcriptional responses between pathogenic and nonpathogenic hantaviruses at 1 day postinfection, suggesting that hantavirus pathogenesis may in part be determined by viral regulation of cellular interferon responses. In contrast to pathogenic NY-1 virus (NY-1V) and Hantaan virus (HTNV), nonpathogenic Prospect Hill virus (PHV) elicits early interferon responses following infection of human endothelial cells. We determined that PHV replication is blocked in human endothelial cells and that RNA and protein synthesis by PHV, but not NY-1V or HTNV, is inhibited at 2 to 4 days postinfection. The addition of antibodies to beta interferon (IFN-β) blocked interferon-directed MxA induction by >90% and demonstrated that hantavirus infection induces the secretion of IFN-β from endothelial cells. Coinfecting endothelial cells with NY-1V and PHV resulted in a 60% decrease in the induction of interferon-responsive MxA transcripts by PHV and further suggested the potential for NY-1V to regulate early IFN responses. Expression of the NY-1V G1 cytoplasmic tail inhibited by >90% RIG-I- and downstream TBK-1-directed transcription from interferon-stimulated response elements or β-interferon promoters in a dose-dependent manner. In contrast...

STUDIES ON PERSISTENT INFECTIONS OF TISSUE CULTURES : IV. EVIDENCE FOR THE PRODUCTION OF AN INTERFERON IN MCN CELLS BY MYXOVIRUSES

Henle, Werner; Henle, Gertrude; Deinhardt, Friedrich; Bergs, Victor V.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 30/09/1959 Português
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In previous reports of this series, it was shown that persistent infection of MCN cultures with certain myxoviruses rendered the cells insusceptible to superinfection by several cytopathogenic viruses. It was thought that production of an interferon might be the cause of this resistance and efforts to confirm this suggestion have been presented. Addition of ultraviolet-inactivated myxoviruses (mumps, Newcastle disease, influenza A, and Sendai) to MCN cultures for periods of 2 to 3 hours, followed by washing and refeeding of the cells, led to the subsequent release into the media of a substance which induced in fresh MCN cells a transitory resistance to infection by vesicular stomatitis virus, and prevented incomplete reproductive cycles of influenza A and Sendai viruses. Media containing this substance were free of detectable hemagglutinating activity and viral complement-fixing antigens. The substance was not neutralized by specific antiviral sera; it was not sedimentable by high speed centrifugation; it was not adsorbed onto red cells; but it was inactivated by trypsin. Thus, its properties matched those of the interferon described by Isaacs and his associates. A comparison of the extent of resistance induced in MCN cells by decreasing doses of ultraviolet-inactivated myxoviruses (interference test) and the protection afforded by the media removed from the cultures prior to challenge and transferred to fresh MCN tubes (interferon test) revealed that wherever interference became detectable in the cells...

THE INFLUENCE OF CORTISONE ON EXPERIMENTAL VIRAL INFECTION : VII. KINETICS OF INTERFERON FORMATION AND ITS INHIBITION WITH HYDROCORTISONE IN RELATION TO VIRAL STRAIN AND VIRULENCE

Smart, K. Marilyn; Kilbourne, Edwin D.
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 31/01/1966 Português
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A comparative study was undertaken of the pathogenesis of infection of the allantoic sac of the chick embryo with three influenza viruses of differing virulence, and of the influence of hydrocortisone on the course of infection. Judged on the basis of earlier onset and greater degree of inflammatory response and diminished survival time of infected embryos, Mel. and Lee viruses were markedly more virulent than PR8, despite the earlier appearance of virus in PR8-infected embryos. Interferon appeared first and in greater quantity in the allantoic fluid of Lee-infected embryos and latest with PR8 infection. Thus, there was no correlation of avirulence and better interferon production with the viruses under study in the present system. Furthermore, evidence obtained suggested that Lee virus ("virulent") was most susceptible to interferon action, and also that viral synthesis in the chorioallantoic membrane with PR8 ("avirulent") persisted after the appearance of interferon. The injection of hydrocortisone within 2 hr of the initiation of infection delayed the synthesis of all three viruses; had no significant effect upon the inflammatory response; and transiently inhibited the synthesis of interferon, while prolonging the survival of Lee- and Mel.-infected embryos. Late administration of hydrocortisone suppresses both the inflammatory response and the production of interferon. Only in the case of Lee virus infection did hydrocortisone administration lead to augmentation of final yields of virus with the low infection multiplicity employed in the present experiments. It is postulated that Lee virus is a better inducer of interferon because its infectivity in vivo is more rapidly inactivated. As a consequence synthesis of Lee virus is more under the control of endogenous interferon than is the case with PR8 or Mel. virus. Therefore...

Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/05/1978 Português
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Interferon, induced in lymphocytes either with viruses or cell lines, increases severalfold the natural cytotoxicity of human lymphocytes on target cell lines. Cell separation experiments support the hypothesis that interferon enhances the activity of natural killer cells rather than generating a new population of effector cells. In mixed culture of lymphocytes and cell lines in which endogenous interferon is produced, interferon mediates an enhancement of cytotoxicity that represents up to 70-90% of the observed cytotoxicity. The effect of interferon on target cells is antagonistic to the effect on the lymphocytes: the susceptibility to cell-mediated lysis of various cells upon pretreatment with interferon is decreased and in some cases almost completely suppressed. Interferon renders target cells resistant to natural killer cells acting by an intracellular mechanism which requires RNA and protein synthesis. While normal fibroblasts are protected, virus-infected cells and most tumor cells usually are not protected by interferon. Interferon by stimulating very efficient nonspecific cytotoxic cells and by protecting at the same time normal cells from lysis, might render the natural killer cell system an inducible selective defense mechanism against tumor and virus-infected cells.

Interferon inhibits the generation of allospecific suppressor T lymphocytes

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/06/1982 Português
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26.61%
The effect of human interferon alpha on the differentiation of functional populations of lymphocytes during the human allogeneic response in vitro was studied. Interferon alpha inhibited the generation of allospecific suppressor T lymphocytes that normally develop from lymphocytes primed in vitro against allogeneic cells. This effect was not the result of the destruction by interferon of precursor suppressor cells but rather to inhibition of their differentiation into active suppressor T lymphocytes. This inhibition was reversible and could be overcome by repeated allogeneic stimulation even in the presence of interferon. Inhibition of the generation of allospecific suppressor lymphocytes by interferon might play an important role in the allogeneic response. Interferon inhibited the proliferation of lymphocytes after allogeneic stimulation in a primary mixed lymphocyte reaction but enhanced their cytotoxicity. Despite the inhibitory effect in the primary mixed lymphocyte reaction, the specific secondary proliferative response of lymphocytes primed against a single HLA-DR antigen was only slightly affected by interferon. On the other hand, the nonspecific secondary proliferative response of lymphocytes primed in the presence of interferon was significantly reduced...

Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. I. Rapid evolution of encephalomyocarditis virus infection

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 02/11/1976 Português
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The role of interferon in the pathogenesis of encephalomyocarditis (EMC) virus infection was determined by treating mice with potent, partially purified sheep anti-mouse interferon globulin. In control mice, EMC virus was present in low titers in various visceral organs but attained high titers in the brain towards the 4th to 5th day, at which time mice died with signs of central nervous system disease. In mice treated with anti-mouse interferon globulin, virus was present in high titer in visceral organs 24--36 h after viral inoculation and virtually all mice were dead by 45 h. This rapid evolution of EMC virus infection was not observed in mice treated with the globulin fraction prepared from a normal sheep, from a sheep exhibiting a low anti-mouse interferon-neutralizing titer, nor from a sheep having a high titer of antibody to human leukocyte interferon. The experimental results indicated that anti-interferon globulin neutralized the interferon liberated by virus-infected cells, thus permitting extensive virus multiplication in several visceral organs. We conclude that interferon is an important early component of host resistance to this virus infection.

Interferon-γ Released by Gluten-Stimulated Celiac Disease-Specific Intestinal T Cells Enhances the Transepithelial Flux of Gluten PeptidesS⃞

Bethune, Michael T.; Siegel, Matthew; Howles-Banerji, Samuel; Khosla, Chaitan
Fonte: American Society for Pharmacology and Experimental Therapeutics Publicador: American Society for Pharmacology and Experimental Therapeutics
Tipo: Artigo de Revista Científica
Português
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Celiac sprue is a T-cell-mediated enteropathy elicited in genetically susceptible individuals by dietary gluten proteins. To initiate and propagate inflammation, proteolytically resistant gluten peptides must be translocated across the small intestinal epithelium and presented to DQ2-restricted T cells, but the effectors enabling this translocation under normal and inflammatory conditions are not well understood. We demonstrate that a fluorescently labeled antigenic 33-mer gluten peptide is translocated intact across a T84 cultured epithelial cell monolayer and that preincubation of the monolayer with media from gluten-stimulated, celiac patient-derived intestinal T cells enhances the apical-to-basolateral flux of this peptide in a dose-dependent, saturable manner. The permeability-enhancing activity of activated T-cell media is inhibited by blocking antibodies against either interferon-γ or its receptor and is recapitulated using recombinant interferon-γ. At saturating levels of interferon-γ, activated T-cell media does not further increase transepithelial peptide flux, indicating the primacy of interferon-γ as an effector of increased epithelial permeability during inflammation. Reducing the assay temperature to 4°C reverses the effect of interferon-γ but does not reduce basal peptide flux occurring in the absence of interferon-γ...