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Gamma interferon suppresses acute and chronic Trypanosoma cruzi infection in cyclosporin-treated mice.

McCabe, R; Meagher, S; Mullins, B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1991 Português
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To determine if exogenous gamma interferon is effective in immunosuppressed mice infected with Trypanosoma cruzi, recombinant murine gamma interferon was administered to cyclosporin-treated mice with either acute or chronic T. cruzi infection. Gamma interferon significantly decreased parasitemia and prevented death in acutely infected mice. Parasitemias and mortality of mice treated with both gamma interferon and cyclosporin were similar to those of immunocompetent controls. In chronically infected mice, cyclosporin treatment produced significantly more organ explant cultures positive for T. cruzi. Fewer positive cultures, particularly for spleen and heart, were obtained from cyclosporin-treated mice when they also received gamma interferon. Ketoconazole treatment of mice resulted in no positive cultures. Cyclosporin treatment did not prevent activation of peritoneal macrophages by parenteral gamma interferon, nor did it have a consistent effect on serum titers of alpha/beta or gamma interferon in response to a second challenge inoculum of T. cruzi. These data indicate that exogenous gamma interferon suppresses acute and chronic T. cruzi infection in cyclosporin-treated mice but that gamma interferon is not as effective as the relatively specific antimicrobial ketoconazole. Gamma interferon activates macrophages despite cyclosporin treatment...

Recombinant mouse interferon-gamma regulation of antibody production.

Johnson, H M; Torres, B A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1983 Português
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Interferon-gamma produced in monkey cells by transfection with mouse interferon-gamma cDNA suppressed the mouse in vitro antibody response in a manner similar to that of natural mouse interferon-gamma. Significant suppression was obtained with as little as 1 U of interferon. Recombinant human interferon-gamma produced by cloning in a similar fashion was not suppressive. Both the suppressive and the antiviral activities of recombinant interferon-gamma were neutralized by antibodies to mouse natural interferon-gamma. Thus, interferon-gamma was responsible for the immunosuppression. At the cellular level, the recombinant interferon-gamma was capable of activating macrophages to suppress antibody production. The data provide clear-cut evidence that interferon-gamma plays an important role in regulation of immunological processes.

Heterogeneity of interferon mRNA species from Sendai virus-induced human lymphoblastoid (Namalva) cells and Newcastle disease virus-induced murine fibroblastoid (L) cells.

Sagar, A D; Pickering, L A; Sussman-Berger, P; Stewart, W E; Sehgal, P B
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 10/01/1981 Português
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Cytoplasmic polyadenylated RNA preparations obtained from Sendai-induced human lymphoblastoid (Namalva) cells and from Newcastle disease virus (NDV)-induced murine (L) cells were denatured in 10-12.5 mM CH3HgOH and then electrophoresed in 2% agarose tube gels containing 10 mM CH3HgOH, the RNA eluted from gel slices and translationally active interferon mRNA species located using the Xenopus oocyte assay. The interferons synthesized were characterized as alpha or beta types based on neutralization tests using specific antisera against human or murine interferon-alpha and interferon-beta. At least two species of mRNA for human interferon-alpha and two for human interferon-beta were detected in RNA from Sendai-induced Namalva cells. These are (approximate mRNA length in parentheses) alpha (1.3 kb), alpha (1.9 kb), beta (1.1 kb) and beta (1.9 kb). Two populations of murine interferon mRNA of lengths approximately 1.4 kb and 3 kb were detected in mRNA preparations from NDV-induced L cells by electrophoresis. However, since the translation products of each of these two populations of mRNA consist of both murine interferon-alpha and murine interferon-beta it is likely that both the 1.4 kb and 3 kb populations contain at least one species each of murine interferon-alpha and murine interferon-beta mRNA.

Entrapment of human leukocyte interferon in the aqueous interstices of liposomes.

Anderson, P; Vilcek, J; Weissmann, G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /03/1981 Português
Relevância na Pesquisa
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Human leukocyte interferon has been trapped in the aqueous interstices of multilamellar liposomes (phosphatidylcholine, dicetyl phosphate, and cholesterol [7:2:1]). Such liposomes trapped [3H]inulin (aqueous space marker) and interferon to the extent of 0.22 +/- 0.01 mg (n = 8) and 350 +/- 54 U (n = 4) per mumol of liquid, respectively, as judged by molecular sieve chromatography. Interferon trapped within liposomes was resistant to tryptic digestion under conditions which completely inactivated free interferon. Studies in which interferon was added to preformed liposomes excluded the possibility that interferon bound nonspecifically to the outer layer of the multilamellar liposomes. When interferon was added to the aqueous medium in which liposomes of various net surface charges were permitted to form, trapping of interferon varied directly with the interlamellar aqueous compartments of the liposomes. The demonstration that stable liposomes can entrap interferon suggests that these may constitute suitable vectors for the delivery of interferon to cells.

Combined Antiviral Effects of Interferon, Adenine Arabinoside, Hypoxanthine Arabinoside, and Adenine Arabinoside-5′-Monophosphate in Human Fibroblast Cultures

Bryson, Yvonne J.; Kronenberg, L. H.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1977 Português
Relevância na Pesquisa
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Adenine arabinoside and human interferon are currently being evaluated in clinical trials against herpes- and poxvirus infections. Interferon production is also a normal antiviral response. It is therefore important to examine the combined actions of interferon and antiviral arabinosides for possible synergy or antagonism. We have examined the antiviral activities of human fibroblast interferon, adenine arabinoside, hypoxanthine arabinoside, and adenine arabinoside 5′-monophosphate individually, using plaque inhibition of vaccinia and herpes simplex type 2 viruses in human skin fibroblast cultures. By combining doses of interferon and arabinosides that, acting alone, give intermediate degrees of plaque inhibition, we were able to compare the combined antiviral activity with that calculated from the activity of each inhibitor alone, assuming that the activities are statistically independent. Our results show that the plaque-inhibitory activities of interferon and the arabinosides tested are statistically independent. The results also show that the arabinosides do not destabilize the antiviral state previously induced by interferon, and that interferon pretreatment does not interfere with subsequent arabinoside action in infected cells. We have also found that arabinosides do not affect the induction of interferon synthesis by either Newcastle disease virus or double-stranded ribonucleic acid...

Interferon-directed inhibition of chronic murine leukemia virus production in cell cultures: lack of effect on intracellular viral markers.

Friedman, R M; Chang, E H; Ramseur, J M; Myers, M W
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1975 Português
Relevância na Pesquisa
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Extracellular murine leukemia virus (MLV) reverse transcriptase activity was decreased by interferon treatment in four interferon-sensitive mouse cell lines which were chronic MLV producers. In three cell lines which were relatively insensitive to interferon, extracellular enzyme activity remained unchanged by interferon treatment. The concentrations of interferon used had no effect on DNA synthesis or cell replication of AKR,C+ cells which were chronic producers of AKR-MLV. In AKR,C+ cultures interferon treatment also had no effect on the level of intracellular viral reverse transcriptase activity in spite of an inhibition of extracellular enzyme activity. Treatment of AKRC+ cultures with interferon for 9 days inhibited extracellular viral reverse transcriptase levels throughout the period of treatment; however, the intracellular enzyme activity remained unchanged, and concentrations of viral p30 (gs) antigen were increased in the interferon-treated cells. When the cells were washed to remove interferon, however, virus production rapidly rose and intracellular p30 antigen fell to the levels of untreated AKR,C+ cells. These and previously reported results suggested that in interferon-treated AKR,C+ cells virus production is inhibited at a late step in the MLV replication cycle...

Murine cytomegalovirus: induction of and sensitivity to interferon in vitro.

Oie, H K; Easton, J M; Ablashi, D V; Baron, S
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1975 Português
Relevância na Pesquisa
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Moderate amounts of viral inhibitor were produced by mouse embryo (ME) cultures infected with two strains of plaque-purified murine cytomegalovirus (MCV). This inhibitor was shown to be interferon, based on the possession of similar properties. The growth studies of MCV in ME cells showed that interferon was produced as early as 4 h after infection, infectious virus was produced between 12 to 16 h, and cytopathic effect was produced between 16 to 18 h. Since MCV-induced interferon production and the subsequent development of antiviral state occurred early, the long eclipse period may be due to an interferon-mediated delay of virus replication. Pretreatment of ME cells with varying concentrations of interferon before infection with MCV did not result in increased interferon production, but at high pretreatment doses a slight inhibitory effect on interferon production was observed. In vitro sensitivity studies showed that small doses of MCV were highly sensitive to the antiviral action of interferon, but higher viral doses proved to be markedly resistant. Although the available evidence does not permit a definitive interpretation of the mechanism by which MCV may show differing sensitivities to interferon action, the presence of a small interferon-resistant fraction of virus-infected cells may account for the observations.

Studies on the Mechanism of the Priming Effect of Interferon on Interferon Production by Cell Cultures Exposed to Poly(rI) · Poly(rC)

De Clercq, Erik; Stewart, William E.; De Somer, Pierre
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1973 Português
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Interferon induction by poly(rI)·poly(rC) in primary rabbit kidney and mouse L-929 cell cultures was markedly increased if the cells were previously treated with homologous interferon. This priming effect has been established with different times of exposure of the cells to poly(rI)·poly(rC), and was most pronounced for short pulses of contact of the polynucleotide with the cells (10 s, 1 min). Treatment of the cells with pancreatic ribonuclease immediately after their exposure to poly(rI)·poly(rC) brought about a relatively greater reduction of the interferon response in interferon-primed cells than it did in unprimed cell cultures. Priming of the cells with interferon did not increase cell-binding of poly(rI)·poly(rC), whether this cell-binding was measured quantitatively (by radioactivity, upon exposure of the cells to radiolabeled polymer) or qualitatively (by antiviral activity, by assaying the cell extract for virus plaque reduction). Similarly, interferon priming did not alter the sensitivity of cell-associated poly(rI)·poly(rC) to extraneous ribonuclease treatment. Finally, priming with interferon did not decrease the rate of degradation of cell-bound poly(rI)·poly(rC) by cellular nucleases nor did it increase the anti-nuclease potency of the cells. The exact mechanism by which previous exposure of the cells to interferon enhances subsequent interferon production...

Interferon Synthesis in X-Irradiated Animals V. Origin of Mouse Serum Interferon Induced by Polyinosinic-Polycytidylic Acid and Encephalomyocarditis Virus

Jullien, Pierre; De Maeyer-Guignard, Jaqueline; De Maeyer, Edward
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1974 Português
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The radioresistant cell systems producing serum interferon after intravenous administration of polyinosinic-polycytidylic acid [poly(I·C)] or encephalomyocarditis virus in mice were studied in rat-to-mouse radiation chimeras. Interferon induced by poly(I·C) became of donor type within 3 months after grafting of irradiated C3H/He mice with Wistar rat bone marrow cells; this indicated that it was made in cells derived from the hemopoietic system. In contrast, encephalomyocarditis virus-induced interferon remained of recipient type in xenogeneic chimeras up to 3 months after grafting, which indicated that the bulk of this interferon originated from a cell population not derived from the hemopoietic system. To ascertain that the respective radiosensitivities of the systems producing rat interferon in chimeras corresponded to that of normal mice, some rat-to-mouse chimeras were subjected to a second X irradiation 1 month after the first irradiation and restoration. Circulating interferon production was studied 4 days later. As expected, the re-irradiation strongly depressed rat serum interferon production induced by Newcastle disease virus but had no effect on rat interferon synthesis induced by poly (I·C). These results point to a macrophage origin for the bulk of poly(I·C)-induced circulating interferon.

Alpha-interferon inhibits the expression of heavy chain mu messenger RNA in Daudi cells.

Meurs, E; Hovanessian, A G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1988 Português
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A clone of Daudi cells (Daudi-S) synthesizes the heavy chain of IgM (mu-chain) under routine conditions of cell culture. In the presence of alpha-interferon, however, synthesis of mu-chain is decreased rapidly at a time when the overall protein synthesis is not modified and the dsRNA-dependent protein kinase and the 2-5A synthetase are induced. This inhibition of mu-chain synthesis seems to be correlated with the antiproliferative action of interferon since it occurs only slightly in another clone of Daudi cells resistant (Daudi-R) to the antiproliferative action of interferon. In these resistant cells, however, the protein kinase and the 2-5A synthetase are induced by interferon. Specific inhibition of mu-chain synthesis in interferon-treated Daudi-S cells is a consequence of decreased steady-state levels of mu-chain mRNA. This effect occurs 4-8 h after addition of interferon in parallel with decreased levels of c-myc mRNA and enhanced levels of HLA mRNA. Reduced levels of mu-chain mRNA in interferon-treated Daudi-S cells is not a consequence of its enhanced degradation as shown by actinomycin D chase experiments. Furthermore, nuclear run on experiments rule out an effect on the transcription of mu-chain mRNA. Therefore, the inhibitory mechanism mediated by interferon might be at the level of termination and/or post-transcriptional processing of mu-chain RNA. In contrast...

Cytotoxic cells induced during lymphocytic choriomeningitis virus infection of mice: natural killer cell activity in cultured spleen leukocytes concomitant with T-cell-dependent immune interferon production.

Welsh, R M; Doe, W F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /11/1980 Português
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The characteristics and specificities of spleen and peritoneal cytotoxic cells generated during lymphocytic choriomeningitis virus (LCMV) infection of C3H/St mice were examined. Activated natural killer (NK) cell activity was identified in fresh leukocyte populations from the 2nd to 8th days postinfection, whereas virus-specific cytotoxic T-cell activity was detected from the 6th to 14th days. When leukocytes were cultured overnight at 37 degrees C before assay, T-cell activity was still observed, but nonspecific activated NK cell-like cytotoxicity was only detected on the 6th and to a lesser degree the 8th day postinfection. Overnight culture of leukocytes taken earlier in the infection eliminated their NK cell activity. Similar activities were seen with spleen cell, plastic-adherent peritoneal cell, and nonadherent peritoneal cell populations. The virus-specific cytotoxicity observed with adherent peritoneal cells was due to contamination with cytotoxic T cells, as shown by H-2-restricted cytotoxicity and sensitivity to anti-theta antibody and complement. The nonspecific cultured day 6 effector cell from either the spleen or peritoneum displayed killing specificities and other physical properties identical to those of activated NK cells...

Depression of viral interferon induction in cell monolayers by coal dust

Hahon, Nicholas
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1974 Português
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Habon, N. (1974).British Journal of Industrial Medicine,31, 201-208. Depression of viral interferon induction in cell monolayers by coal dust. Studies on the induction of interferon by influenza virus revealed that this adaptive cellular response was depressed completely or partially in coal dust-treated human or simian cell monolayers. Maximal inhibition of interferon production occurred with coal particles ranging in size from < 2·0 to 19·1 μM and with coal dust concentrations ranging from 0·1 to 0·001 g per 3 × 107 cells. The longer coal dust remained in contact with cells before the addition of viral inducer, the more likely was interferon production inhibited. Interferon depression was independent of the rank and geographic source of coal dust and of the virus/cell multiplicity of infection. Enhanced interferon yields resulted in normal and coal dust-treated cells when they were pretreated or proned with interferon. Neither interferon antagonists, interference with virus-cell integration, nor adsorption by coal dust accounted for the depression of interferon yields. The data suggest that coal particles per se act on cells in a subtle manner to interpose in the inductive process of interferon synthesis.

Antiproliferative effects of interferon alpha on human pancreatic carcinoma cell lines are associated with differential regulation of protein kinase C isoenzymes.

Rosewicz, S; Weder, M; Kaiser, A; Riecken, E O
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1996 Português
Relevância na Pesquisa
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BACKGROUND: The molecular mechanisms mediating the antiproliferative effects of interferon alpha on human pancreatic carcinoma cells are poorly understood. AIM: To characterise the effects of interferon alpha on protein kinase C isoenzyme expression in interferon alpha sensitive and resistant human pancreatic tumour cell lines. METHODS: The ductal human pancreatic carcinoma cell lines Capan 1 and Capan 2 were investigated. Anchorage dependent and independent growth was determined by cell number and a human tumour clonogenic assay. Interferon alpha receptor expression was examined by reverse-transcriptase polymerase chain reaction and electrophoretic mobility shift assay. Protein kinase C isoenzyme expression was evaluated by western blotting using monospecific polyclonal antibodies. RESULTS: Interferon alpha treatment results in a time and dose dependent inhibition of anchorage dependent and independent growth in Capan 1 cells while Capan 2 cells were not affected by interferon alpha. Both cell lines express interferon alpha receptor mRNA transcripts. Growth inhibition by interferon alpha in Capan 1 cells was paralleled by a profound decrease of protein kinase C alpha and zeta expression while these isoenzymes were unaffected in the interferon resistant cell line Capan 2. CONCLUSION: Inhibition of protein kinase C isoenzyme expression might determine the sensitivity of a given pancreatic carcinoma to respond to the antiproliferative action of interferon alpha.

In vitro production and cellular origin of murine type II interferon.

Sonnenfeld, G; Mandel, A D; Merigan, T C
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /04/1979 Português
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Antigen-specific type II interferon was produced in vitro by harvesting supernatants of spleen cell cultures from Swiss-Webster mice sensitized with Mycobacterium bovis strain BCG and challenged with old tuberculin. Treatment of C3H mouse spleen cell cultures with appropriate anti-Ia, anti-IgG, anti-Thy-1 or anti-Ly-2,3 sera resulted in a significant decrease in production of type II interferon. Removal of nylon wool adherent cells or cells with histamine receptors by column chromatography similarly caused reduced production of type II interferon. Recombination of spleen cell cultures treated with anti-Ia and anti-Thy-1 sera or of cells treated with anti-IgG and anti-Thy-1 resulted in restored production of type II interferon. Interferon production was also restored by combination of cells passed through histamine columns with anti-Ia treated cells, or those passed through nylon wool columns with anti-Thy-1 treated cells. Anti-Ly-1 serum treatment had no effect on interferon production. Removal of plastic-adherent cells or cells that had phagocytosed carbonyl iron also decreased interferon production, suggesting that macrophages were also involved in type II interferon production. Recombination of non-adherent spleen cells with anti-Ia and anti-Thy-1 sera treated spleen cells...

Mode of regulation of natural killer cell activity by interferon

Minato, N; Reid, L; Cantor, H; Lengyel, P; Bloom, BR
Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/07/1980 Português
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Whereas xenogeneic tumors such as baby hamster kidney or HeLa cells grow in nude mice, the same cells persistently infected with a variety of viruses are rejected. Spleen cells from normal nude mice were found to be induced to produce interferon and to exert natural killer (NK) activity on virus persistently infected (PI) tumor cells, and not on uninfected parental cells in vitro. The phenotype of the interferon-producing cells and the NK effector cells was found to be the same namely, Qa 5(+), Ly 5(+), ganglio-N- tetraosylceramide, with 35 percent of the NK cells also expressing Thy 1.2. NK activity against virus PI tumor cell lines could be nonspecifically augmented both in vivo and in vitro by prior contact with virus PI tumor cells. It was unambiguously demonstrated with chemically homogeneous mouse interferon that interferon, and not a contaminant, was responsible for the augmentation of NK activity in vitro. Studies on the mode of interferon action in augmenting NK activity revealed that the target cell for interferon action was serologically distinct from the NK effector cell. Anti-Ly 5 + complement (C)-treated spleen cells were depleted of NK activity and the ability to produce interferon, but, upon incubation with interferon for 1-3 h...

Immune interferon produced to high levels by antigenic stimulation of human lymphocytes with influenza virus

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/11/1981 Português
Relevância na Pesquisa
26.62%
Influenza virus stimulation of human lymphocytes induced high levels of immune interferon in lymphocyte cultures. The lymphocytes of normal adults produced approximately 1,000 U/10(6) cells, which was in large part gamma interferon. The lymphocytes of individuals recently vaccinated yielded very high levels (10-50,000 U/10(6) cells) of interferon. The interferon was pH 2 labile, and was not neutralized by antisera to alpha or beta interferon. It did not bind to a monoclonal antibody to alpha interferon, and after partial purification it had characteristics identical to human gamma interferon induced by phytohemagglutinin. The highest yields were produced by treatment of stimulator cells with live virus. Stimulation by whole inactivated virus resulted in lower levels of interferon, and purified hemagglutinin did not induce interferon. The antigen responsible for stimulating the lymphocyte response and interferon induction is a cross- reactive determinant present on all human and non-human influenza viruses tested.

Role of interferon in the pathogenesis of virus diseases in mice as demonstrated by the use of anti-interferon serum. II. Studies with herpes simplex, Moloney sarcoma, vesicular stomatitis, Newcastle disease, and influenza viruses

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 02/11/1976 Português
Relevância na Pesquisa
26.62%
The effect of potent sheep anti-mouse interferon globulin was investigated in several different experimental virus diseases of mice. In anti-interferon globulin-treated mice infected intraperitoneally with herpes simplex virus (HSV) type I, the latent period was shortened, and the overall LD50 was increased several hundredfold compared to virus-infected control mice. When HSV was inoculated subcutaneously all anti-interferon globulin-treated mice died, whereas only 5% of virus-infected control mice died. Subsequent treatment with anti-interferon globulin of previously HSV-infected mice did not result in reactivation of HSV. Treatment of adult mice with anti-interferon globulin resulted in an earlier appearance of MSV-induced tumors, a greater number of mice bearing tumors, an increase in tumor size, and an increase in the duration of tumors. All tumors eventually regressed despite reinjection of anti-interferon globulin. Anti-interferon globulin treatment resulted in a rapid onset of disease and death in adult mice inoculated (intranasal) with VSV and in newborn mice infected with NDV. Anti-interferon globulin exerted no effect on the course of influenza virus infection of mice. We conclude that the early production of interferon is an importane element in the response of the mouse to several viruses exhibiting different pathogeneses.

Neutralization of Interleukin-10 from CD14+ Monocytes Enhances Gamma Interferon Production in Peripheral Blood Mononuclear Cells from Mycobacterium avium subsp. paratuberculosis-Infected Goats▿

Lybeck, Kari R.; Storset, Anne K.; Olsen, Ingrid
Fonte: American Society for Microbiology (ASM) Publicador: American Society for Microbiology (ASM)
Tipo: Artigo de Revista Científica
Português
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The gamma interferon assay is used to identify Mycobacterium avium subsp. paratuberculosis-infected animals. It has been suggested that regulatory mechanisms could influence the sensitivity of the test when it is performed with cells from cattle and that the neutralization of interleukin-10 (IL-10) in vitro would increase the gamma interferon responses. To investigate the regulatory mechanisms affecting the gamma interferon assay with cells from goats, blood was collected from M. avium subsp. paratuberculosis-infected, M. avium subsp. paratuberculosis-exposed, and noninfected goats. Neutralization of IL-10 by a monoclonal antibody resulted in increased levels of gamma interferon production in M. avium subsp. paratuberculosis purified protein derivative (PPDj)-stimulated samples from both infected and exposed goats. However, the levels of gamma interferon release were also increased in unstimulated cells and in PPDj-stimulated cells from some noninfected animals following neutralization. Depletion of putative regulatory CD25high T cells had no clear effect on the number of gamma-interferon-producing cells. The IL-10-producing cells were identified to be mainly CD14+ major histocompatibility complex class II-positive monocytes in both PPDj-stimulated and control cultures and not regulatory T cells. However...

Human Plasmacytoid Dendritic Cell Accumulation Amplifies Their Type 1 Interferon Production

Liao, Anne P; Salajegheh, Mohammad; Morehouse, Chris; Nazareno, Remedios; Jubin, Ronald G; Jallal, Bahija; Yao, Yihong; Greenberg, Steven A
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
26.62%
To determine the potential consequences of plasmacytoid dendritic cell (pDC) accumulation in tissue sites observed in several autoimmune diseases, we measured type 1 interferon production from circulating human pDCs as a function of pDC concentration. The effects of interferon-alpha and blockade of the type 1 interferon receptor (IFNAR) on human pDC type 1 interferon and interferon-inducible transcription and protein production were measured. Human pDCs became far more efficient producers of interferon-alpha at concentrations beyond those normally present in blood, through an IFNAR-dependent mechanism. Extracellular interferon-alpha increased pDC production of type 1 interferons. The accumulation of pDCs in diseased tissue sites allows marked non-linear amplification of type 1 interferon production locally. The role of the IFNAR-dependent mechanism of interferon production by human pDCs is greater than previously suggested. IFNAR blockade has potential for diminishing type 1 interferon production by all human cells.

Myeloid Dendritic Cells from B6.NZM Sle1/Sle2/Sle3 Lupus-prone Mice express an Interferon Signature that Precedes Disease Onset

Sriram, Uma; Varghese, Linda; Bennett, Heather L.; Jog, Neelakshi R.; Shivers, Debra K.; Ning, Yue; Behrens, Edward M.; Caricchio, Roberto; Gallucci, Stefania
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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Patients with systemic lupus erythematosus (SLE) show an over-expression of Type I Interferon (IFN) responsive genes called “Interferon Signature”. We found that the B6.NZMSle1/Sle2/Sle3 (Sle1,2,3) lupus-prone mice also express an Interferon Signature compared to non autoimmune C57BL/6 mice. In vitro, myeloid dendritic cells (mDCs)(GM-CSF bone marrow-derived BMDCs) from Sle1,2,3 mice constitutively over-expressed IFN responsive genes such as IFNb, Oas-3, Mx-1, ISG-15 and CXCL10, and the members of IFN signaling pathway STAT1, STAT2, and IRF7. The Interferon Signature was similar in Sle1,2,3 BMDCs from young, pre-autoimmune mice and from mice with high titers of autoantibodies, suggesting that the Interferon Signature in mDCs precedes disease onset and it is independent from the autoantibodies. Sle1,2,3 BMDCs hyper-responded to stimulation with IFNa and the TLR7 and TLR9 agonists R848 and CpGs. We propose that this hyper-response is induced by the Interferon Signature and only partially contributes to the Signature, since oligonucleotides inhibitory for TLR7 and TLR9 only partially suppressed the constitutive Interferon Signature and pre-exposure to IFNa induced the same hyper-response in wild type BMDCs than in Sle1,2,3 BMDCs. In vivo...