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Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome

LIMA, Renata. L. L. Ferreira de; HOPER, Sarah A.; GHASSIBE, Michella; COOPER, Margaret E.; RORICK, Nicholas K.; KONDO, Shinji; KATZ, Lori; MARAZITA, Mary L.; COMPTON, John; BALE, Sherri; HEHR, Ute; DIXON, Michael J.; DAACK-HIRSCH, Sandra; BOUTE, Odile; BA
Fonte: LIPPINCOTT WILLIAMS & WILKINS Publicador: LIPPINCOTT WILLIAMS & WILKINS
Tipo: Artigo de Revista Científica
Português
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Purpose: Interferon regulatory factor 6 encodes a member of the IRF family of transcription factors. Mutations in interferon regulatory factor 6 cause Van der Woude and popliteal pterygium syndrome, two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic Mutations in interferon regulatory factor 6 between two large geographically distinct collections of families with Van der Woude and between one collection of families with popliteal pterygium syndrome. Methods: We performed direct sequence analysis of interferon regulatory factor 6 exons oil samples from three collections, two with Van der Woude and one with popliteal pterygium syndrome. Results: We identified mutations in interferon regulatory factor 6 exons in 68% of families in both Van der Woude collections and in 97% of families with popliteal pterygium syndrome. In sum, 106 novel disease-causing variants were found. The distribution of mutations in the interferon regulatory factor 6 exons in each collection was not random; exons 3, 4, 7, and 9 accounted for 80%. In the Van der Woude collections, the mutations were evenly divided between protein truncation and missense, whereas most mutations identified in the popliteal pterygium syndrome collection were missense. Further...

Prevalence and nonrandom distribution of exonic mutations in interferon regulatory factor 6 in 307 families with Van der Woude syndrome and 37 families with popliteal pterygium syndrome

Lima, Renata. L. L. Ferreira de; Hoper, Sarah A.; Ghassibe, Michella; Cooper, Margaret E.; Rorick, Nicholas K.; Kondo, Shinji; Katz, Lori; Marazita, Mary L.; Compton, John; Bale, Sherri; Hehr, Ute; Dixon, Michael J.; Daack-Hirsch, Sandra; Boute, Odile; Ba
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica Formato: 241-247
Português
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Purpose: Interferon regulatory factor 6 encodes a member of the IRF family of transcription factors. Mutations in interferon regulatory factor 6 cause Van der Woude and popliteal pterygium syndrome, two related orofacial clefting disorders. Here, we compared and contrasted the frequency and distribution of exonic Mutations in interferon regulatory factor 6 between two large geographically distinct collections of families with Van der Woude and between one collection of families with popliteal pterygium syndrome. Methods: We performed direct sequence analysis of interferon regulatory factor 6 exons oil samples from three collections, two with Van der Woude and one with popliteal pterygium syndrome. Results: We identified mutations in interferon regulatory factor 6 exons in 68% of families in both Van der Woude collections and in 97% of families with popliteal pterygium syndrome. In sum, 106 novel disease-causing variants were found. The distribution of mutations in the interferon regulatory factor 6 exons in each collection was not random; exons 3, 4, 7, and 9 accounted for 80%. In the Van der Woude collections, the mutations were evenly divided between protein truncation and missense, whereas most mutations identified in the popliteal pterygium syndrome collection were missense. Further...

An Essential Role for Gamma Interferon in Innate Resistance to Shigella flexneri Infection

Way, Sing Sing; Borczuk, Alain C.; Dominitz, Rene; Goldberg, Marcia B.
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/1998 Português
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Shigella spp. are the major cause of bacillary dysentery worldwide. To identify immune effectors associated with protection of the naive host during infection, the susceptibility to pulmonary Shigella infection of each of various mouse strains that have a targeted deletion in a specific aspect of the immune system was evaluated. Our results demonstrate that mice deficient in gamma interferon are 5 orders of magnitude more susceptible to Shigella than are wild-type mice, whereas mice deficient in B and T lymphocytes or in T lymphocytes alone exhibit no difference in susceptibility. Significantly lower numbers of shigellae were recovered from immunocompetent compared with gamma-interferon-deficient mice after infection. While immunocompetent mice were able to clear a sublethal Shigella inoculum by day 5 postinfection, progressively increasing numbers of shigellae were cultured from the lungs of gamma interferon-deficient mice over the same period. Histopathology of the lungs from immunocompetent mice infected with a sublethal Shigella inoculum showed mild inflammatory changes, whereas the lungs from gamma interferon-deficient mice demonstrated progressively worsening acute bronchiolitis with ulceration. Further, the time to death in gamma interferon-deficient mice correlates inversely with the size of the Shigella inoculum. To identify the cellular source of gamma interferon...

Interferon-independent and -induced regulation of Epstein-Barr virus EBNA-1 gene transcription in Burkitt lymphoma.

Nonkwelo, C; Ruf, I K; Sample, J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1997 Português
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Replication of the Epstein-Barr virus (EBV) genome within latently infected cells is dependent on the EBV EBNA-1 protein. The objective of this study was to identify transcriptional regulatory proteins that mediate EBNA-1 expression via the viral promoter Qp, which is active in EBV-associated tumors such as Burkitt lymphoma and nasopharyngeal carcinoma. Results of a yeast one-hybrid screen suggested that a subset of the interferon regulatory factor (IRF) family may regulate EBNA-1 transcription by targeting an essential cis-regulatory element of Qp, QRE-2. Further investigation indicated that the transcriptional activator IRF-1 and the closely related IRF-2, a repressor of interferon-induced gene expression, are both capable of activating Qp. However, the major QRE-2-specific binding activity detected within extracts of Burkitt lymphoma cells was attributed to IRF-2, suggesting that interferon-independent activation of Qp is largely mediated by IRF-2 in these cells. We observed no effect of gamma interferon on Qp activity in transfection assays, whereas we observed a moderate but significant repression of Qp activity in response to alpha interferon, possibly mediated by either the interferon consensus sequence binding protein or IRF-7...

Effect of interferon on the growth of Chlamydia trachomatis in mouse fibroblasts (L cells).

Rothermel, C D; Byrne, G I; Havell, E A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1983 Português
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The effect of murine interferon on the growth of the lymphogranuloma venereum biotype of Chlamydia trachomatis (strain 440L) in murine fibroblasts (L cells) was examined. Treatment of infected cell cultures with interferon caused a reduction in the number of inclusion-bearing cells as seen by light and electron microscopy and a decrease in yields of chlamydiae as determined by infectivity assays. Interferon also inhibited cycloheximide-resistant (chlamydia-specific) protein synthesis in infected cells. The interferon effect was dose dependent, with 80 to 90% inhibition occurring at concentrations of greater than 200 IU/ml. The inhibitory effect was neutralized by anti-murine interferon globulin. Interferon did not inactivate extracellular chlamydiae, and both host cell RNA and protein synthesis were required for the development of the interferon-induced antichlamydial state. Inhibition of chlamydial growth by interferon was demonstrable in cells treated 18 h before infection or up to 4 h after infection. Cells infected after interferon was removed exhibited an antichlamydial activity decline which was complete by 30 h after interferon removal. We show that interferon treatment did not affect either entry of chlamydiae into host cells or chlamydial conversion to reticulate bodies but rather caused a reduction in the rate of reticulate body replication.

Component(s) of Sendai virus that can induce interferon in mouse spleen cells.

Ito, Y; Hosaka, Y
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1983 Português
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To identify the active component of Sendai virus that induces interferon in mouse spleen cells, infectious and noninfectious viruses, envelope particles derived from them, and isolated hemagglutinin-neuraminidase (HN) glycoproteins were examined for interferon induction. The interaction between membranous structures containing Sendai virus HN glycoprotein and the receptors on the cell surface was shown to be sufficient for interferon induction in mouse spleen cells, suggesting that the actual inducer of interferon in mouse spleen cells is the HN glycoprotein of Sendai virus. When mouse spleen cells were stimulated in vitro with Sendai virus grown in eggs or LLC-MK2 cells or with membranous structures containing glycoproteins obtained from these viruses, interferon could be detected in the culture fluid. Furthermore, isolated HN glycoprotein per se could induce interferon in the cells. A linear correlation was found between the titer of interferon induced and the hemagglutinating activity of the membranous structure containing the HN glycoprotein. It was concluded from these findings that HN glycoprotein was the active component of Sendai virus responsible for interferon induction in mouse spleen cells and that viral RNA and F glycoprotein were not required. The results also showed that the interaction between HN glycoprotein and receptors on the cell surface triggered production of type I interferon (IFN-alpha and IFN-beta). Although when Sendai virus was incubated at 56 degrees C for 5 min it lost its hemolytic and hemagglutinating activities...

Le interferon mRNA from human fibroblasts.

Pang, R H; Hayes, T G; Vilcek, J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1980 Português
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Human F and Le interferon can be clearly distinguished on the basis of different antigenic properties and host range. After inoculation with Newcastle disease virus (NDV), GM-258 fibroblasts produced Le as well as F interferon; in contrast, only F interferon was detectable after stimulation with poly(I) . poly(C). Polyadenylylated mRNA isolated from fibroblasts induced with poly(I) . poly(C) or NDV was injected into Xenopus laevis oocytes and the interferon activities thus produced were analyzed. Only F interferon production was demonstrable in oocytes injected with mRNA from cells induced with poly(I) . poly(C), whereas both F and Le interferons were made in oocytes injected with mRNA from NDV-induced cultures. The time course of accumulation of F and Le interferon mRNAs in NDV-induced cells corresponded to the kinetics of F and Le interferon synthesis in intact cells. The ratio of F and Le interferons made in oocytes was similar to that observed in intact GM-258 cells. F and Le interferon mRNA activities isolated from GM-258 cells could not be separated by sucrose density gradient centrifugation. However, the profile of F mRNA activity was more heterogeneous and its peak sedimented somewhat more slowly than that of Le interferon mRNA. These results suggest that the varying ratios of F and Le interferon synthesis in different cells after different modes of stimulation are determined at the level of mRNA. The induction mechanisms of F and Le interferon mRNA synthesis appear to be closely related but not identical.

Priming: a Nonantiviral Function of Interferon 1

Stewart, William E.; Gosser, Lynn B.; Lockart, Royce Z.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1971 Português
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No interferon is made by L cells when they are infected with MM virus. However, several thousand units of interferon are produced when interferon-treated L cells are infected with MM virus. We call the conversion of cells, from nonproducers to producers, priming. The time required for cells to become fully primed is dependent on the interferon concentration with which they are incubated. Primed cells produced interferon earlier than normal cells stimulated by other inducers. Cells which were exposed to interferon in the presence of inhibitors of protein synthesis became fully primed yet developed no virus resistance. Also, primed cells produced interferon in response to low concentrations of polyriboinosinic acid · polyribocytidylic acid that did not induce interferon in normal cells. Therefore, priming appears to be a function of interferon separable from its antiviral activity. Several other picornaviruses that failed to induce interferon in L cells, human embryonic lung cells, or monkey kidney cells did induce interferon when these cells had been primed by homologous interferons.

Herpes Simplex Virus 1 Gene Products Occlude the Interferon Signaling Pathway at Multiple Sites

Chee, Ana Virginia; Roizman, Bernard
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
Publicado em /04/2004 Português
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Earlier studies have shown that herpes simplex virus 1 (HSV-1) blocks the interferon response pathways, at least at two sites, by circumventing the effects of activation of protein kinase R by double-stranded RNA and interferon and through the degradation of promyelocytic leukemia protein (PML) since interferon has no antiviral effects in PML−/− cells. Here we report on two effects of viral genes on other sites of the interferon signaling pathway. (i) In infected cells, Jak1 kinase associated with interferon receptors and Stat2 associated with the interferon signaling pathway rapidly disappear from infected cells. The level of interferon alpha receptor is also reduced, albeit less drastically at times after 4 h postinfection. Other members of the Stat family of proteins were either decreased in amount or posttranslationally processed in a manner different from those of mock-infected cells. The decrease in the levels of Jak1 and Stat2 may account for the decrease in the formation of complexes consisting of Stat1 or ISGF3 and DNA sequences containing the interferon-stimulated response elements after exposure to interferon. (ii) The disappearance of Jak1 and Stat2 was related at least in part to the function of the virion host shutoff protein...

Two levels of regulation of beta-interferon gene expression in human cells.

Raj, N B; Pitha, P M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1983 Português
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We cloned alpha- and beta-interferon cDNA and used them as specific probes to determine the relative levels of interferon mRNA in human fibroblasts cells induced with poly(rI).poly(rC) or Newcastle disease virus to synthesize interferon. Both inducers activated only the beta-interferon gene; however, the half life of beta-interferon mRNA in cells induced with virus was substantially longer than in poly(rI).poly(rC)-induced cells. The transcription rate of beta-interferon RNA sequences was examined in nuclei isolated from poly(rI).poly(rC)-induced cells; it was found that the induction leads to transcriptional activation of the beta-interferon gene and that the shutoff period when no interferon synthesis or cytoplasmic betamRNA are detected. Thus, the synthesis of beta interferon in poly(rI).poly-(rC)-induced human fibroblasts is controlled both by activation of transcription of the beta-interferon gene and by alteration of the beta-interferon mRNA stability.

Mechanism of stimulation of natural killer-cell cytotoxicity by interferon and an interferon-inducer in the rat.

Flexman, J P; Shellam, G R
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1981 Português
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The interferon-induced Newcastle disease virus (NDV) was shown to augment cytotoxicity attributable to natural killer (NK) cells in all of the major lymphoid organs of W/Fu rats except the thymus. The levels of interferon isolated from the spleen following NDV inoculation correlated with the increase in splenic cytotoxicity from the same spleen. Spleen-derived interferon was shown to augment splenic cytotoxicity following intravenous inoculation, and to augment spleen cell cytotoxicity in vitro. Three major peaks of interferon type I were found in spleen homogenates corresponding to mol. wt of greater than 100,000, 29-33,000 and 19-23,000. All these fractions stimulated spleen cell cytotoxicity when tested in vitro. The rapid drop in splenic cytotoxicity 24 hr after NDV inoculation was associated with a rapid fall in interferon levels in vivo. The need for the continued presence of interferon for the stimulation of cytotoxicity was demonstrated when spleen cells pretreated with interferon for 4 hr in vitro lost their augmented cytotoxicity upon culturing for a further 20 hr in the absence of interferon. Although splenic cytotoxicity returned to control levels within 24 hr of a single 10(7.3) EID50 dose of NDV, repeated doses of NDV maintained augmented cytotoxicity over a longer period. Spleen cells either taken from rats injected with NDV or pretreated in vitro with interferon showed a two-fold increase in the number of cytotoxic cells bound to W/FuG-1 target cells...

Interferon suppresses pinocytosis but stimulates phagocytosis in mouse peritoneal macrophages: related changes in cytoskeletal organization

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/04/1984 Português
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Treatment of thioglycolate-elicited macrophages with mouse beta- interferon markedly reduces pinocytosis of horseradish peroxidase and fluorescein isothiocyanate (FITC)-dextran but stimulates phagocytosis of IgG-coated sheep erythrocytes. Experiments with FITC-dextran have revealed that the overall decrease in pinocytosis is due to a nearly complete inhibition of pinocytosis in a large fraction of interferon- treated macrophages. In the remaining cells pinocytosis continues at a rate similar to that in untreated control cells. A considerable reduction in the number of cells pinocytosing FITC-dextran was observed within 12 h from the beginning of interferon treatment. Measurement of the overall level of pinocytic activity with horseradish peroxidase showed a progressive decline through 72 h of treatment. In the interferon-sensitive subpopulation, there were marked changes in cytoskeletal organization. Microtubules and 10-nm filaments were aggregated in the perinuclear region while most of the peripheral cytoplasm became devoid of these cytoskeletal structures as observed by fluorescence and electron microscopy. In addition, interferon treatment of macrophages appeared to disrupt the close topological association between bundles of 10-nm filaments and organelles such as mitochondria...

Interferon Alpha in Systemic Lupus Erythematosus

Niewold, Timothy B.; Clark, Daniel N.; Salloum, Rafah; Poole, Brian D.
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
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The pleiotropic cytokine interferon alpha is involved in multiple aspects of lupus etiology and pathogenesis. Interferon alpha is important under normal circumstances for antiviral responses and immune activation. However, heightened levels of serum interferon alpha and expression of interferon response genes are common in lupus patients. Lupus-associated autoantibodies can drive the production of interferon alpha and heightened levels of interferon interfere with immune regulation. Several genes in the pathways leading to interferon production or signaling are associated with risk for lupus. Clinical and cellular manifestations of excess interferon alpha in lupus combined with the genetic risk factors associated with interferon make this cytokine a rare bridge between genetic risk and phenotypic effects. Interferon alpha influences the clinical picture of lupus and may represent a therapeutic target. This paper provides an overview of the cellular, genetic, and clinical aspects of interferon alpha in lupus.

The Nitric Oxide Pathway Provides Innate Antiviral Protection in Conjunction with the Type I Interferon Pathway in Fibroblasts

Mehta, Devangi R.; Ashkar, Ali A.; Mossman, Karen L.
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 21/02/2012 Português
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The innate host response to virus infection is largely dominated by the production of type I interferon and interferon stimulated genes. In particular, fibroblasts respond robustly to viral infection and to recognition of viral signatures such as dsRNA with the rapid production of type I interferon; subsequently, fibroblasts are a key cell type in antiviral protection. We recently found, however, that primary fibroblasts deficient for the production of interferon, interferon stimulated genes, and other cytokines and chemokines mount a robust antiviral response against both DNA and RNA viruses following stimulation with dsRNA. Nitric oxide is a chemical compound with pleiotropic functions; its production by phagocytes in response to interferon-γ is associated with antimicrobial activity. Here we show that in response to dsRNA, nitric oxide is rapidly produced in primary fibroblasts. In the presence of an intact interferon system, nitric oxide plays a minor but significant role in antiviral protection. However, in the absence of an interferon system, nitric oxide is critical for the protection against DNA viruses. In primary fibroblasts, NF-κB and interferon regulatory factor 1 participate in the induction of inducible nitric oxide synthase expression...

Endogenous Interferon-β-Inducible Gene Expression and Interferon-β-Treatment Are Associated with Reduced T Cell Responses to Myelin Basic Protein in Multiple Sclerosis

Börnsen, Lars; Romme Christensen, Jeppe; Ratzer, Rikke; Hedegaard, Chris; Søndergaard, Helle B.; Krakauer, Martin; Hesse, Dan; Nielsen, Claus H.; Sorensen, Per S.; Sellebjerg, Finn
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 04/03/2015 Português
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Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-β is used for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels of interferon-β-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients, whereas other studies reported an association with a poor response to treatment with interferon-β. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-β-inducible genes in peripheral blood mononuclear cells and interferon-β-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-β-treated multiple sclerosis patients had increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro...

Untersuchungen zur Modulation der Aktivitäten der Cathepsine B, L und S in endosomalen und lysosomalen Fraktionen menschlicher Monozyten/Makrophagen; Modulation of the activity of cathepsins B, L and S in endosomal and lysosomal fractions of human monocytes/macrophages

Sauerbrei, Ramona Katharina Elisabeth
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
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Monozyten als professionell antigenpräsentierende Zellen spielen eine wichtige Rolle beim Abbau phagozytierten Materials und darüber hinaus dessen Präsentation als Antigen. Diese Prozesse hängen von Cathepsinen ab, die in den Endosomen und Lysosomen der Zelle lokalisiert sind. Daher wurden Expression und Aktivität der Cathepsine B, L und S in diesen Kompartimenten von menschlichen Monozyten/Makrophagen untersucht, die aus Buffy coats frisch isoliert oder mit 100 U/ml Interferon-gamma kultiviert wurden. Die Ergebnisse dieser Arbeit zeigen, daß in frisch isolierten Monozyten die Cathepsinaktivitäten der endosomalen Fraktion um ein Vielfaches höhere Werte aufzeigen als die Cathepsin-Aktivitäten in der lysosomalen Fraktion. Im Gegensatz dazu zeigen 72 Stunden lang in Kontrollmedium kultivierte Zellen höchste Cathepsinaktivitäten in der lysosomalen Fraktion. Mit Interferon-gamma stimulierte Zellen wiesen das gleiche endosomale/lysosomale Verteilungsmuster auf, jedoch mit unterschiedlichen Veränderungen der Cathepsinaktivitäten in diesen Kompartimenten. Interferon-gamma führte in den Zellen zu einer Hochregulation der MHC Klasse II-Moleküle aller drei Cathepsine sowie des Cysteinproteinasen-Inhibitors Cystatin C. Dabei zeigten die Lysosomen eine größere Zunahme der Cathepsin B-Aktivität als die Endosomen. Dagegen waren die Aktivitäten von Cathepsin L und S in den Endosomen nur auf 150 % und 167 % erhöht...

Functional equivalents of interferon-mediated signals needed for induction of an mRNA can be generated by double-stranded RNA and growth factors.

Tiwari, R K; Kusari, J; Sen, G C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1987 Português
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In our earlier studies we demonstrated that in HeLaM cells, interferon-alpha produces two functionally distinguishable signals, both of which are needed for induced transcription of mRNA 561 and other inducible mRNAs. Interferon-gamma cannot induce mRNA 561 because it produces only signal 1. Here we report that platelet-derived growth factor or epidermal growth factor could also produce signal 1. On the other hand, signal 2, which can be produced by interferon-alpha but not by interferon-gamma, could be elicited also by double-stranded RNA. Several lines of evidence suggest that the production of signal 2 by double-stranded RNA was not mediated through interferon. Interferon-induced transcription of mRNA 561 in HeLaM cells or in human fibroblast GM2767 cells was transient. However, in interferon-alpha-treated GM2767 cells, which had ceased to synthesize mRNA 561, transcription of this mRNA could be induced effectively by double-stranded RNA suggesting that this induction process could bypass the interferon-mediated down-regulation of induced transcription. Unlike HeLaM and GM2767 cells, in Daudi cells, induction of mRNA 561 by interferon-alpha was not transient. Transcription of this and two other induced mRNAs continued at a high rate even after 18 h of interferon-alpha treatment of these cells. The lack of down-regulation of interferon-induced gene expression may be responsible for interferon's acute antigrowth effects on these cells.

Interferon-alpha (IFN-alpha) production by human intestinal mononuclear cells. Response to virus in control subjects and in Crohn's disease.

Capobianchi, M R; Fais, S; Mercuri, F; Boirivant, M; Dianzani, F; Pallone, F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1992 Português
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The virus induced production of interferon alpha by human intestinal lamina propria mononuclear cells was investigated. Intestinal and autologous peripheral cells from control subjects and patients with Crohn's disease were cultured in vitro with and without stimulation with the Newcastle disease virus. Interferon alpha was measured and characterised in the culture supernatants after 12 hours and the kinetics of production was evaluated over the following four days of culture. No detectable interferon alpha was found in cultures of unstimulated intestinal and autologous peripheral mononuclear cells from controls and Crohn's disease whereas interferon alpha was released in all cultures stimulated with the virus. In all 12 hours experiments in both groups, virus stimulated intestinal mononuclear cells yielded significantly less interferon alpha than the autologous peripheral cells. The kinetics experiments showed that control intestinal mononuclear cells appeared to be poorly responsive to virus stimulation showing a release of interferon alpha significantly lower than that of the autologous peripheral cells. The interferon alpha release at day 4 by control cells (either intestinal or peripheral) did not differ from that measured after the first 12 hours. In contrast...

Abnormal behavior of interferon-induced enzymatic activities in an interferon-resistant cell line.

Verhaegen, M; Divizia, M; Vandenbussche, P; Kuwata, T; Content, J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1980 Português
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Interferon induces two double-stranded RNA-dependent enzymatic activities: an oligoisoadenylate synthetase that converts ATP to ppp(A2'p)n5'A, and a protein phosphokinase. We have explored the level and inducibility of these two enzymes in a human cell line (HEC-1) totally insensitive to both the antiviral and the anticellular actions of interferon. The activities of both enzymes are high in untreated cells and only minor changes occur after treatment with interferon, even at high concentrations. Interferon-treated HEC-1 cells do not contain an inhibitor of the oligoisoadenylate synthetase activity. The products of this HEC-1 oligoisoadenylate synthetase consist mainly of dimers, trimers, and tetramers as found in other cell lines after interferon treatment. The synthetase level is unaffected by treating the cells with anti-interferon antiserum, indicating that the results cannot be explained by a spontaneous low production of interferon by these cells. Furthermore, virus multiplication is not inhibited, even after treatment with interferon. These observations suggest that either the two enzymatic activities do not suffice for the establishment of an antiviral state in vivo or that a regulatory control mechanism, lost in these cells and common for both enzymes...

Polymorphism discovery and association analyses of the interferon genes in type 1 diabetes

Morris, Gerard A. J.; Lowe, Christopher E.; Cooper, Jason D.; Payne, Felicity; Vella, Adrian; Godfrey, Lisa M.; Hulme, John S.; Walker, Neil M.; Healy, Barry C.; Lam, Alex C.; Lyons, Paul A.; Todd, John A.
Fonte: Universidade de Cambridge Publicador: Universidade de Cambridge
Tipo: Article; Published Version
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RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.; Abstract Background The aetiology of the autoimmune disease type 1 diabetes (T1D) involves many genetic and environmental factors. Evidence suggests that innate immune responses, including the action of interferons, may also play a role in the initiation and/or pathogenic process of autoimmunity. In the present report, we have adopted a linkage disequilibrium (LD) mapping approach to test for an association between T1D and three regions encompassing 13 interferon alpha (IFNA) genes, interferon omega-1 (IFNW1), interferon beta-1 (IFNB1), interferon gamma (IFNG) and the interferon consensus-sequence binding protein 1 (ICSBP1). Results We identified 238 variants, most, single nucleotide polymorphisms (SNPs), by sequencing IFNA, IFNB1, IFNW1 and ICSBP1, 98 of which where novel when compared to dbSNP build 124. We used polymorphisms identified in the SeattleSNP database for INFG. A set of tag SNPs was selected for each of the interferon and interferon-related genes to test for an association between T1D and this complex gene family. A total of 45 tag SNPs were selected and genotyped in a collection of 472 multiplex families. Conclusion We have developed informative sets of SNPs for the interferon and interferon related genes. No statistical evidence of a major association between T1D and any of the interferon and interferon related genes tested was found.