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1

Seleno-organic compounds induce interferon and tumor necrosis factor in human but not in rat or mouse lymphoid

100%

Inglot A. D., Piasecki E., Zaczynska E., Zielinska-Janczylik J.

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vol. 40

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issue 2

169-173

EN

The seleno-organic compounds are highly active in several anti-inflammatory assays performed in mice and rats. However, they differ from the classical non-steroidal anti-inflammatory drugs including indomethacin despite the fact that both types of drugs are inhibitors of prostaglandins and leukotrienes. Furthermore, ebselen and analogs are potent anti-oxudants in many animal cell cultures. The toxicity of the drugs is low because selenium in their structure is not bioavailable. We have discovered that the seleno-organic compounds induce interferon gamma tumor necrosis factor alpha and other cytokines in human peripheral blood leukocytes (PBL). Furthermore, the action of the drugs and PHA or Con A was synergistic. However, ebselen and analogs were found to be inactive as the cytokine inducers in cultured rat or mouse lymphoid cells. In cotrast to their effects in human PBL, the drugs even inhibited the production of IFN-gamma after stimulation with PHA or Con A. The inhibition was dose dependent. We suggest that the induction of IFN by ebselen and analogs is species specific and it may depend on interaction of the drugs with a specific receptor and/or signal-transducing system present in human but not in some animal cells.

2

Effect of granulocyte-macrophage colony stimulating growth factor on interferon and tumor necrosis factor production in whole blood cell cultures of patients with acute myelogenous leukemia

80%

Kaminska T., Hus I., Dmoszynska A., Kandefer-Szerszen M.

Archivum Immunologiae et Therapiae Experimentalis

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2001

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vol. 49

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issue 2 suppl.

83-88

EN

The effect of recombinant human granulocyte-macrophage colony-stimulating growth factor (rHuGM-CSF) treatement on in vitro interferon (IFN) and tumor necrosis factor (TNF) production in peripheral blood cells of 46 patients with acute myelogenous leukemia (AML) was examined. GM-CSF significant enhanced virus-induced IFN- production in blood cells (containing 70% of blasts) of 28 patients with M4-M5 AML according to the French-American-British (FAB) classification and also phytohemagglutinin (PHA)-induced IFN- production in blood cells (containing 68% of blasts) of 18 patients with AML M0-M3 type. In control blood cells (25 healthy persons) GM-CSF enhanced PHA-induced IFN- but did not influence IFN- production. In the presence of GM-CSF, TNF- titers induced with lipopolysaccharide were also higher in control blood cells but not in cells of patients with M0-M3 or M4-M5 type of AML. The significance of GM-CSF-enhanced IFN- and IFN- production in antimicrobial and antileukemic immune reactions which can develop during GM-CSF therapy is discussed.

3

Mechanisms of type I interferon signaling in normal and malignant cells

80%

Li Y., Srivastava K. K., Platanias L. C.

Archivum Immunologiae et Therapiae Experimentalis

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2004

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vol. 52

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issue 3

156-163

EN

Type I interferons (IFNs) are cytokines that induce multiple biological effects on target cells, including antiviral, antiproliferative, and immunomodulatory activities. Consistent with the pleiotropic nature of these cytokines, multiple signaling pathways are activated during binding of IFNs to the type I IFN receptor. An important signaling cascade activated by type I IFNs is the Jak-Stat pathway. Activation of the Tyk-2 and Jak-1 kinases, and downstream formation of various Stat complexes, mediates IFN-dependent gene transcription for IFN-stimulated genes. In addition to the classic Jak-Stat pathway, type I IFNs activate multiple other pathways, including the insulin receptor substrate-phosphatidylinositol 3'-kinase cascade, the CBL-CrkL pathway, and mitogen-activated protein kinase pathways. There is accumulating evidence that non-Stat IFN-regulated signaling pathways play important roles in the generation of the antiproliferative effects of type I IFNs. In this review, the regulation of various signaling cascades by the type I IFN receptor is summarized and an update on recent advances in the field is provided.

4

Expression on interferon genes in trophoblast; its impact on pregnancy

80%

La Bonnardiere C.

Biotechnologia

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1996

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issue 2

52-67

EN

In mammals, succesful implantation of semi-allogenic conceptus (embryo +trophoblast) in the maternal uterus is still an enigma.Its understanding will require better knowledge of the complex hormonal and immunological "cross-talk" between implanting conceptus and mother.IN several ungulate species, around the time of implantation, the trophoblast synthesizez and secrets interferons (IFNs), known as antiviral and immunomodualtory cytokines.THe IFN induction is transient (6-7 days long)), and reaches high levels in ruminants and pigs.This IFN synthesis in early pregnancy addresses two man questions:1)Is there a specific IFN gene regulation in trophoblast, and what are the molecular determinants of this specificity (coding and regulatory sequences) ? 2)What is (are) the effect(s) ogf IFN synthesis on the physiological and/or immune maternal response ? This area of research might find applications in animal breeding in particulatr through improvement of embryo transfer and increase in fecundity, in several animal species.

5

Individual differentiation of innate antiviral immunity in humans; the role of endogenous interferons and tumor necrosis factor in the immunity of leukocytes

70%

Orzechowska B., Antoszkow Z., Blach-Olszewska Z.

Archivum Immunologiae et Therapiae Experimentalis

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2003

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vol. 51

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issue 1

51-60

EN

The natural antiviral immunity of human lymphocytes, leukocyte from peripheral blood and whole-blood cultures was studied using the method of infection with two viruses belonging to different taxonomic groups, vesicular stomatitis virus (VSV) and encephalomyocarditis virus (EMCV). The kinetics of virus replication in both kinds of cultures and the dependence of culture infection on pre-infection incubation time were studied. When the cultures were infected immediately after preparation, most of them were found to be resistant to the viruses. However, when they were infected after several (1-5) days of incubation, VSV and EMCV multiplied in the cultures to high titers. The time of losing the resistance was individually differentiated. The results indicate the presence of a non-specific antiviral immunity characteristic for individuals. The antiviral immunity of healthy donors was compared with that of people suffering from recurrent infections of the upper respiratory tract. This latter group expressed statistically significant lower innate immunity than healthy donors. However there were no differences in interferon (IFN) and tumor necrosis factor (TNF) production between these groups. In order to examine the contribution of the endogenous IFNs and TNF alpha in maintaining innate immunity, specific antibodies against IFN alpha, IFN beta, IFN gamma and TNF alpha were added to VSV-infected leukocytes resistant to infection. The antibodies reduced the antiviral resistance in 9 of 16 experiments. The results suggest that both: endogenous interferons and TNF alpha may participate in the constitution of innate immunity, though they are not the only mediators of it.

6

The genes of interferons and interferon-related factors: localization and relationships with chromosome aberrations in cancer

61%

Haus O.

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vol. 48

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issue 2

95-100

EN

The paper presents a review of data on the localization of interferons (IFNs) and IFN system genes and their relationship with human diseases, mainly cancer. Genes of interferon system proteins are located at the sites of breakpoints of the structural chromosome aberrations in cancer. Thus, any of them are rearranged or translocated in various tumor types. As the activity of these genes plays a role in cancer development, their rearrangements may be one of the crucial points in the pathogenesis of some cancer types. Besides, they also take part in organism immunity against viral infections. Transfection experiments with IFN system genes have proved the influence of these genes on cancer behavior and may serve as a basis for clinical gene therapy. IFN-alpha and IFN-beta genes are located at 9p21-22, the site of frequent homozygotic deletions in cancer. Their loss sensitizes cells to the growth inhibitory actions of exogenous IFNs. The IFN-gamma gene, a representative of class II genes, is located at 12q24. 1. Transfection of class II IFNs genes to cancer cell lines causes cell proliferation arrest and augments the expression of HLA antigens, which may be clinically useful in stimulating the immune destruction of tumor cells. The interferon regulatory factor 1 (IRF-1) gene is located at 5q31, the site of common deletions in myelodysplastic syndromes (MDS) and secondary leukemias. The loss of heterozygosity of this gene was found in MDS, which proves that IRF-1 may be a tumor suppressor. A transfection of its gene causes neoplastic transformation arrest. The double-stranded RNA-activated protein kinase (PKR) gene is located at 2p21-22, a region which is frequently rearranged in leukemia. Transfection of a wild type PKR gene reverses neoplastic transformation caused by transfection of a mutated PKR gene, proving that PKR acts as a dominant negative cancer suppressor.

7

DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response

61%

Cao W., Hunter R., Strnatka D., McQueen C. A., Erickson R. P.

Journal of Applied Genetics

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2005

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vol. 46

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issue 2

217-225

EN

Arylamine N-acetyltransferase (NAT) genes were targeted for inhibition using short hairpin RNA (shRNA) using two different RNA polymerase III promoters. Constructs were developed for NAT1 and NAT2, the endogenous mouse genes, and for human NAT1. There were fetal and neonatal deaths with these constructs, perhaps due in part to an interferon response as reflected in increases in oligoadenylate synthetase I mRNA levels. Seven out of 8 founders with the U6 promoter generated offspring but only 2 gave positive offspring. Out of 15 founders for H1 promoted constructs, only 4 had positive offspring. When transgenic lines were successfully established, the expression of the targeted genes was variable between animals and was not generally inhibitory.

8

Cytokines in HIV-positive individuals and AIDS patients

51%

Piasecki E.

Postępy Higieny i Medycyny Doświadczalnej

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1995

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vol. 49

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issue 1

125-135

Refine search results

Seleno-organic compounds induce interferon and tumor necrosis factor in human but not in rat or mouse lymphoid

Effect of granulocyte-macrophage colony stimulating growth factor on interferon and tumor necrosis factor production in whole blood cell cultures of patients with acute myelogenous leukemia

Mechanisms of type I interferon signaling in normal and malignant cells

Expression on interferon genes in trophoblast; its impact on pregnancy

Individual differentiation of innate antiviral immunity in humans; the role of endogenous interferons and tumor necrosis factor in the immunity of leukocytes

The genes of interferons and interferon-related factors: localization and relationships with chromosome aberrations in cancer

DNA constructs designed to produce short hairpin, interfering RNAs in transgenic mice sometimes show early lethality and an interferon response

Cytokines in HIV-positive individuals and AIDS patients