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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effects of gamma-interferon (gamma-IFN), retinoic acid (RA), and cytosine arabinoside (ARA-C) on the growth, morphology, and phenotype of the human neuroblastoma (NB) cell lines, LAN-1 and GI-ME-N, have been extensively tested. 2. RA, gamma-IFN, and ARA-C induced a dose-dependent morphological differentiation and growth inhibition, without affecting cell viability. Cells exposed to 10(-6) M RA or 1000 U/ml gamma-IFN significantly decreased their growth rate within the first 24 and 48 hr of culture, respectively. Cells became smaller and polygonal and sprouted long cellular processes with varicosities along their courses. In contrast, ARA-C-differentiated cells were larger and flattened, with few elongated dendritic processes. 3. Analysis of membrane and cytoskeletal markers by immunofluorescence and Western blot showed several changes in NB-specific antigen expression after 5 days of treatment with all inducing agents. Analysis of labeled phosphatidylinositol metabolites from prelabeled cells showed, within 1 min of treatment with RA, a rapid decrease in inositol 1,4,5-trisphosphate and of 1,2-diacylglycerol levels. No changes in inositol phospholipid metabolism were observed in gamma-IFN- or ARA-C-treated cells. 4. We conclude that RA-induced decrease in phosphatidylinositol (PI) hydrolysis is not likely to be a consequence of the acquisition of a different phenotype, as its changes precede the acquisition of neuronal markers. In addition, gamma-IFN and ARA-C, both inducing a mature phenotype, did not affect PI hydrolysis. 5. Decreased PI hydrolysis seems to be sufficient, although not necessary, to commit NB cells to neuronal differentiation. Analysis of molecular mechanisms associated with NB cell differentiation may be helpful to clarify the potential of various biological agents in affecting the development of the neural cell.
Cell Mol Neurobiol 1991 Aug
PMID:Gamma-interferon, retinoic acid, and cytosine arabinoside induce neuroblastoma differentiation by different mechanisms. 175 63

It has been suggested that growth inhibition of cells by interferons may be mediated through interferon induced down-regulation of transferrin receptor expression. We describe a continuously growing cell line UWOV2 (pf) which expresses cell surface transferrin receptor but is able to grow in the absence of transferrin. This cell line is sensitive to the growth inhibitory effects of interferon alpha. Interferon alpha induced growth inhibition is not, however, accompanied by modulation of transferrin receptor expression suggesting that transferrin receptor modulation is not an essential component of the growth inhibitory effect of interferons.
Mol Biother 1991 Sep
PMID:Interferon (IFN) alpha inhibits cell proliferation of UWOV2 cells without down-regulation of transferrin receptors. 176 64

This review focuses on the use of gamma-interferon (gamma-IFN) in cancer therapy. Although clinical trials using gamma-IFN have yet to identify a treatment niche for this cytokine, these studies have led to a greater understanding of the pleiotropic effects of this molecule on the human immune response, as well as identification of the dose range required for optimal biologic response modification. Thus, continued efforts to clinically develop gamma-IFN are warranted.
Mol Biother 1991 Dec
PMID:Applications of gamma-interferon in cancer therapy. 176 69

Forty-three dogs and cats with spontaneous tumors were treated with the immunostimulating polysaccharide acemannan by intraperitoneal and intralesional routes of administration. Tumors from 26 of these animals showed histopathological evidence of immunological attack as shown by marked necrosis or lymphocytic infiltration. Thirteen showed moderate to marked tumor necrosis or liquefaction. Twenty-one demonstrated lymphoid infiltration, and seven demonstrated encapsulation. Twelve animals showed obvious clinical improvement as assessed by tumor shrinkage, tumor necrosis, or prolonged survival; these included five of seven animals with fibrosarcomas. It is believed that acemannan exerts its antitumor activity through macrophage activation and the release of tumor necrosis factor, interleukin-1, and interferon.
Mol Biother 1991 Dec
PMID:Efficacy of acemannan in treatment of canine and feline spontaneous neoplasms. 176 73

Two Saccharomyces cerevisiae strains containing integrated copies of the MAT alpha 1 gene fused to the PHO5 promoter have been obtained by transformation of a MAT alpha 1 mutant. The strains differ in length of 5'-uncoding region of the MAT alpha 1 in the integrated constructions. The mating activity and the ability of these strains to express the yeast MF alpha 1 gene and the hyman alpha-N-interferon gene under the control of MF alpha 1 promoter was shown to be regulated by the exogenous inorganic phosphate. The level of intracellular alpha-N-interferon synthesized in these strains was several fold higher as compared with the wild type alpha mating type strain. At the same time the observed increase in intracellular production is not accompanied by an increase in the level of secreted alpha-N-interferon. On the contrary, one of the strains had a two-fold reduction in the rate of secretion.
Mol Gen Mikrobiol Virusol 1991 Dec
PMID:[Preparation of Saccharomyces cerevisiae strains with regulated MFalpha1 promotor activity]. 178 39

The dynamics of protein kinases activity in nuclear and cytoplasmic fractions of human fibroblasts treated by preparations of natural and synthetic dsRNA (ridostin, rifastin, larifan and poly(I).poly(C), DEAE-dextran and dsRNA complexes with DEAE-dextran), as well as by preparations of recombinant alpha-2 and beta-1 interferons was obtained. The early activation of enzymes in treated cells extracts and their presence in dsRNA-activated and nonactivated forms were found. In cytoplasmic cellular fractions treated by interferons the dsRNA dependent protein kinases (nonactivated forms- were prevalent.r In contrast, in dsRNA treated cells or dsRNA complexes with DEAE-dextran treated ones the dsRNA independent protein kinases (activated forms) were found, while dsRNA dependent forms induced by interferons were found at later periods. Nuclear protein kinases are mainly dsRNA independent making possible the supposition of their intracellular activation by incoming dsRNA or interferon-induced formation of ds-structures in cellular nuclei. In phosphorylated proteins spectre the 90, 69, 45-40 and 30-35 kDa polypeptides were found. At early intervals in nuclear fractions was found a nuclease resistant and partially EDTA resistant high molecular phosphorylated complex (120 kDa). The complex is, probably, capable of dissociation to low mol mass components. DEAE-dextran induces strong activation of protein kinases in cytoplasm and nuclei and increases the content of activated forms of enzyme in larifan treated cells.
Mol Gen Mikrobiol Virusol 1991 Nov
PMID:[Phosphorylation of proteins in cytoplasmic and nuclear fractions of human cells treated with double-helical RNA and human recombinant interferon type I]. 180 12

Ovine trophoblast protein (oTP) is a polypeptide secreted by ovine trophectoderm from day 11 to 21, which plays a key role in maternal recognition of pregnancy. Structural analyses established that oTP shares extensive homology with class II alpha-interferon (IFN-alpha II) subfamily. Previous screening of an ovine genomic DNA library probed with an oTP cDNA incidently resulted in the isolation of a functional IFN-alpha II gene and two relevant pseudogenes, as shown by sequence analysis and study of expression in eukaryotic COS cells. The expected oTP gene together with a cognate pseudogene was successfully isolated from the series of clones selected from another genomic library probed with the oTP cDNA, using two specific oligonucleotides, each one complementary to a region of oTP cDNA with little homology with the IFN-alpha II gene and related pseudogenes. Southern blotting of ovine genomic DNA indicated the existence of at least five trophoblast IFN-alpha genes or pseudogenes. Nucleotide sequence comparisons showed that the oTP gene exhibits a higher homology (90%) with bovine trophoblast IFN gene (Stewart et al. (1990) J. Mol. Endocrinol. 4, 275-282) than with oIFN-alpha II gene (70%), thus providing evidence that embryonic IFNs constitute a distinct subfamily of IFN-alpha s.
Mol Cell Endocrinol 1991 Apr
PMID:Cloning and structural analysis of two distinct families of ovine interferon-alpha genes encoding functional class II and trophoblast (oTP) alpha-interferons. 182 Sep 71

The promoter of the gene encoding a cytoplasmic guanylate-binding protein (GBP) contains two overlapping elements: the interferon stimulation response element (ISRE), which mediates alpha interferon (IFN-alpha)-dependent transcription, and the IFN-gamma activation site (GAS), which is required for IFN-gamma-mediated stimulation. The ISRE binds a factor called ISGF-3 that is activated by IFN-alpha but not by IFN-gamma. The GAS binds a protein that is activated by IFN-gamma, which we have termed GAF (IFN-gamma activation factor; T. Decker, D. J. Lew, J. Mirkovitch, and J. E. Darnell, Jr., EMBO J., in press; D. J. Lew, T. Decker, I. Strehlow, and J. E. Darnell, Jr., Mol. Cell. Biol. 11:182-191, 1991). We now find that the GAS is also an IFN-alpha-responsive element in vivo and that IFN-alpha (in addition to activating ISGF-3) rapidly activates a GAS-binding factor, the IFN-alpha activation factor (AAF). The AAF has characteristics very similar to those of the previously described GAF. Through the use of inhibitors of protein synthesis and inhibitors of protein kinases, the activation conditions of AAF, GAF, and ISGF-3 could be distinguished. Therefore, not only do IFN-alpha and IFN-gamma stimulate transcription of GBP through different receptors linked to different signaling molecules, but occupation of the IFN-alpha receptor apparently leads to the rapid activation of two different DNA-binding proteins through the use of different intracellular pathways.
Mol Cell Biol 1991 Oct
PMID:Two distinct alpha-interferon-dependent signal transduction pathways may contribute to activation of transcription of the guanylate-binding protein gene. 183 31

The ability of the central nervous system to produce the cytokine interleukin-1 beta (IL-1 beta) in response to challenge by activators of the mononuclear phagocyte system has been examined in vivo. Unilateral injection of a mixture of gamma-interferon (IFN-gamma) and lipopolysaccharide (LPS) into the forebrain of adult rats induced expression of IL-1 beta mRNA. In situ hybridization of IL-1 beta mRNA showed a gradient of cellular hybridization, which was most intense at the site of IFN-gamma/LPS injection. The reverse transcription--polymerase chain reaction (RT-PCR) was used to demonstrate the presence of IL-1 beta mRNA in normal rat brain, and to confirm increases in IL-1 beta mRNA levels following IFN-gamma/LPS injection. These studies show that IL-1 beta can be induced to high levels within the CNS as a consequence of exposure to potent stimulators of macrophage activation.
Brain Res Mol Brain Res 1991 Jan
PMID:Induction of interleukin-1 beta mRNA in adult rat brain. 185 69

The gene encoding a 67-kDa cytoplasmic guanylate-binding protein (GBP) is transcriptionally induced in cells exposed to interferon of either type I (alpha interferon [IFN-alpha] or type II (IFN-gamma). The promoter of the GBP gene was cloned and found to contain an IFN-alpha-stimulated response element, which mediated the response of the GBP gene to IFN-alpha. On the basis of transfection experiments with recombinant plasmids, two different elements were delineated. Both were required to obtain the maximal response of the GBP gene to IFN-gamma: the IFN-alpha-stimulated response element and an overlapping element termed the IFN-gamma activation site. Different proteins that act on each element were investigated, and their possible involvement in IFN-gamma-induced transcriptional regulation is discussed.
Mol Cell Biol 1991 Jan
PMID:Overlapping elements in the guanylate-binding protein gene promoter mediate transcriptional induction by alpha and gamma interferons. 189 61


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