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

Interferons (IFNs) play a key role in the defense against virus infection and the regulation of cell growth and differentiation, in part through changes in specific gene transcription in target cells. We describe several differences between the signal transduction events that result in transcriptional activation of the human gene coding for a guanylate-binding protein (GBP) by alpha interferon (IFN-alpha) and gamma interferon (IFN-gamma). Activation by IFN-alpha was rapid, transient, and cycloheximide resistant. Activation by IFN-gamma was slower, sustained, and delayed by cycloheximide. IFN-gamma led to the formation of a stable intracellular signal which led to continued GBP transcription even if the ligand was withdrawn, whereas IFN-alpha-induced GBP transcription decayed rapidly if IFN-alpha was withdrawn. Perturbations of signaling pathways involving classical second messengers (cyclic AMP, Ca2+, protein kinase C) did not induce GBP transcription. However, various kinase inhibitors blocked the transcriptional response to IFN-gamma but not IFN-alpha, suggesting that a specific and possibly novel kinase is involved in gene activation by IFN-gamma.
Mol Cell Biol 1989 Dec
PMID:Alpha interferon and gamma interferon stimulate transcription of a single gene through different signal transduction pathways. 255 98

A panel of 27 rodent-human somatic cell hybrids composed of cells of hematopoietic (nonadherent cells) and nonhematopoietic origin (adherent cells) was used to identify the chromosomes involved in the biological response to human IFN-gamma (Hu-IFN-gamma). We found that the stimulation of class-I histocompatibility antigen expression correlates with the presence of human chromosomes 6 and 21 in adherent cell hybrids, while human chromosome 6 alone is sufficient in nonadherent hybrids. Scatchard analysis of the binding of radiolabeled Hu-IFN-gamma to nonadherent cell hybrids gave a Kd value similar to that found on human cell lines. Induction of a reporter gene placed under the transcriptional control of the interferon responsive sequence (IRS) in adherent cell hybrids requires both chromosomes 6 and 21. The antiviral protection by Hu-IFN-gamma in adherent cell hybrids was reached at physiological doses (2 units/ml) when human chromosomes 6 and 21 were present, while higher doses of Hu-IFN-gamma (5000 units/ml) were required for hybrids lacking chromosome 21. Thus, we demonstrate that differences exit in the response to Hu-IFN-gamma depending on the origin of the cell type.
Somat Cell Mol Genet 1989 Nov
PMID:Characterization of human IFN-gamma response using somatic cell hybrids of hematopoietic and nonhematopoietic origin. 255

Human chromosome 6 encodes both the interferon gamma receptor as well as the class I major histocompatibility complex antigens, HLA-A, -B, and -C. However, the presence of chromosome 6 in somatic cell hybrids is insufficient to confer sensitivity to human interferon gamma (Hu-IFN-gamma) as assayed by class I HLA induction; it is necessary for both human chromosomes 6 and 21 to reside in the hybrid to generate a response to Hu-IFN-gamma. Treatment of such a hamster-human hybrid, Q72-18, with Hu-IFN-gamma induces the class I HLA antigens. Q72-18 cells selected by fluorescence-activated cell sorting for the loss of class I HLA induction also lost human chromosome 21. Fusions of such cells to a hybrid that contains only human chromosome 21 reconstitutes HLA antigen induction by Hu-IFN-gamma. Furthermore, fusions of hybrids containing a translocated human chromosome 6q and the HLA-B7 gene to a line containing only human chromosome 21 or a translocated 21q also reconstitutes HLA-B7 mRNA and antigen induction by Hu-IFN-gamma. Thus the segregation of cells on the basis of a biological effect by fluorescence-activated cell sorting and reconstitution by hybrid fusion provides a strategy by which some biological pathways can be mapped at a chromosomal level.
Somat Cell Mol Genet 1988 Nov
PMID:Chromosome mapping of biological pathways by fluorescence-activated cell sorting and cell fusion: human interferon gamma receptor as a model system. 297 62

Human monoblast-like histiocytic lymphoma cell line U937 was induced by a macrophage activating factor for O2- production (MAF-O) to produce O2- in response to phorbol myristate acetate stimulation. A MAF-O-producing human T-cell hybridoma, F4-29-4, was established which was also found to produce macrophage activating factor for glucose consumption (MAF-G) and colony stimulating factor (CSF) when assayed against mouse bone marrow cells. MAF-O could be successfully separated from CSF but not from MAF-G by phenyl-Sepharose CL-4B chromatography (Phenyl-EG-fraction). To differentiate MAF-O from MAF-G and to explore a route for large scale production of MAF-O and its structural elucidation, total messenger RNA was extracted from a human T-cell hybridoma, clone F4-29-4. This messenger RNA was fractionated on 5-30% sucrose gradient and each fraction was microinjected into Xenopus laevis oocytes. MAF-O activity was found in the supernatant of oocytes injected with messenger RNA sedimentated at about 13.0S, while MAF-G messenger RNA was found to be about 10.5S. The MAF-O activity, synthesized from the injected messenger RNA, was not neutralized with an excess amount of anti-human IFN-gamma anti-serum, suggesting that MAF-O is antigenically different from human IFN-gamma.
Mol Immunol 1987 Mar
PMID:Establishment of a human T-cell hybridoma that produces human macrophage activating factor for superoxide production and translation of messenger RNA of the factor in Xenopus laevis oocyte. 303 55

Regulation of synthesis and turnover of an interferon (IFN)-inducible mRNA, mRNA 561, in HeLa monolayer cells was studied. Cytoplasmic levels of this mRNA were estimated by hybridization analyses with a cDNA clone that we have isolated as a probe. IFN-alpha A induced a high level of this mRNA in a transient fashion, whereas no induction was observed in response to IFN-gamma. Surprisingly little mRNA 561 was induced in cells treated simultaneously with IFN-alpha A and an inhibitor of protein synthesis, suggesting that in addition to IFN-alpha A, an interferon-inducible protein was needed for induction of this mRNA. Apparently this putative protein could be induced by IFN-gamma as well. Thus, although little mRNA 561 was synthesized in cells treated either with IFN-gamma alone or with IFN-alpha A and cycloheximide, a large quantity of this mRNA was induced in cells which had been pretreated with IFN-gamma and then treated with IFN-alpha A and cycloheximide. Once mRNA 561 was induced by IFN-alpha A, it turned over rapidly. This rapid turnover could be blocked by actinomycin D or cycloheximide indicating that another IFN-inducible protein may mediate this process.
Mol Cell Biol 1986 Jun
PMID:Regulation of synthesis and turnover of an interferon-inducible mRNA. 309 8

The role of the immune system in the central nervous system has been elusive. Our original description of Ia bearing cells in the central nervous system was controversial, although it has now been confirmed in a variety of systems in both mouse and humans. The function of Ia bearing cells is however still unclear. Recently, others have shown that astrocytes from rats with EAE could present myelin basic protein to T cell clones; however, no other antigens were tested. We have used the culture systems of McCarthy and DeVellis to produce purified cultures of astrocytes and oligodendroglial cells from newborn mouse brains. Newborn brains were chosen since it is impossible to obtain pure cultures of differentiated brain cells from adult mice. Using these cultures, we showed that astrocyte, but not oligodendrocyte cultures treated with ConA supernatants or recombinant IFN-gamma are able to present antigen to appropriate but not inappropriate T cell hybrids. Untreated cells of either the astrocyte or oligodendroglial cell populations were ineffective at antigen presentation. Concomitant with this increase in antigen presenting ability, follows an increase in both the number and density of MHC class I and class II antigens. Antigen presentation was inhibited by appropriate but not inappropriate anti Ia monoclonal antibodies. Anti class I antibodies were ineffective. Depletion experiments showed that both I-A and I-E molecules are expressed on the antigen presenting cells. Thus, we have been able to show that Ia+ cells derived from pure cultures of astrocytes are able, after induction with IFN-gamma, to present antigen to T cell hybrids. This suggests a possible physiologic role of Ia bearing cells in CNS in initiation of immune responses.
J Mol Cell Immunol 1986
PMID:Induction of antigen presentation ability in purified cultures of astroglia by interferon-gamma. 315 Oct 59

Polyclonal and monoclonal antibodies with specificity for protein Mx (a karyophilic 75,000-dalton protein induced by interferon [IFN] in mouse cells carrying the influenza virus resistance allele Mx+) detected an IFN-induced 80,000-dalton protein in peripheral blood lymphocytes and in fibroblasts of healthy human donors. The human protein, like protein Mx, was induced by IFN-alpha but not by IFN-gamma. Unlike the mouse protein, it was predominantly localized in the cell cytoplasm.
Mol Cell Biol 1985 Aug
PMID:Interferon-induced human protein with homology to protein Mx of influenza virus-resistant mice. 393 24

Previous studies in our laboratory demonstrated that murine cerebral microvessel smooth muscle cells (SMC) activate syngeneic CD4+ T-cells in vitro. These T-cells, or their culture supernatants, in turn, strongly inhibit proliferation of the SMC. The present study focuses on IFN-gamma as a mediator of inhibition of SMC proliferation, and addresses the molecular mechanism of this inhibition. IFN-gamma profoundly reduced the proliferation of murine brain microvessel smooth muscle cells in vitro. Three lines of evidence indicate that nitric oxide contributed to this effect: (1) IFN-gamma-mediated inhibition of proliferation correlated with the quantity of nitrite, a stable breakdown product of nitric oxide, in culture supernatants; (2) the addition of N(g)- monomethyl-l-arginine, and inhibitor of nitric oxide synthesis, restored proliferation to control or near control levels; and (3) the addition of hemoglobin, which has a high affinity for, and thus sequesters nitric oxide, also resulted in significant restoration of the proliferative response. However, the nitric oxide donating chemical sodium nitro-prusside, at concentrations up to 100 microM, had no direct cytostatic effect. These results suggest that nitric oxide is a necessary but insufficient component in IFN-gamma-mediated inhibition of microvessel smooth muscle cell proliferation. TNF-alpha also stimulated nitric oxide production by the smooth muscle cells, but was not as potent as IFN-gamma at inhibiting proliferation. Knowledge of the physiological effects of lymphokines on cells of the brain microvasculature will contribute towards a better understanding of inflammatory processes in diseases such as multiple sclerosis and infectious encephalitis.
Mol Immunol 1995 Sep
PMID:Involvement of nitric oxide in IFN-gamma-mediated reduction of microvessel smooth muscle cell proliferation. 747 2

A synthetic DNA construct has been developed as a standard molecule whereby murine cytokine mRNA molecules can be quantified by the reverse transcription-polymerase chain reaction (RT-PCR). The construct, designated Cytoquant 1, allows the quantification of murine IL-1 alpha, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, IFN-gamma, TNF-alpha, TGF-beta, GM-CSF, CD4, CD8, HPRT and beta-actin mRNA levels. This technique is based on the amplification of a transcribed RNA molecule from Cytoquant 1 as an internal standard control in both the RT and PCR reactions. The quantification data from these analyses are expressed in absolute values, i.e. molecules/cell, which allows the data derived from separate experiments to be compared. In this study, mRNAs encoding beta-actin, IL-10, IFN-gamma and GM-CSF have been quantitated in both Th1 and Th2 cell clones with, and without, stimulation. The quantitative analysis data are highly reproducible and cytokine mRNA concentrations are reflective of restricted cytokine secretion patterns. Furthermore, constitutive cytokine mRNA levels are detectable in resting cells, eliminating the need for exogenous stimulation. The high degree of sensitivity and accuracy make this methodology uniquely suited for the study of T-cell subset cytokine expression in both in vivo and in vitro biological models.
Mol Immunol 1995 Sep
PMID:A synthetic standard DNA construct for use in quantification of murine cytokine mRNA molecules. 747 5

Epithelial damage in the airways is a feature often observed in patients with asthma and is probably caused by the interaction of epithelial cells with leukocytes. As adhesion molecules are thought to be important in this interaction, we analyzed the expression and modulation of adhesion molecules on primary cultured human bronchial epithelial cells and the bronchial epithelial cell lines BEAS-2B and NCI-H292. E-selectin, P-selectin, and VCAM-1 were absent under basal and stimulated conditions. The adhesion molecules ICAM-1 (CD54), LFA-3 (CD58), and CD44 (H-CAM) were expressed basally on primary cultured human bronchial epithelial cells and the BEAS-2B and NCI-H292 cell lines. CD44 and LFA-3 expression did not change after stimulation with IFN-gamma or TNF-alpha. In contrast, ICAM-1 expression on human bronchial epithelial cells and BEAS-2B cells could be increased by incubation with PMA, IFN-gamma, TNF-alpha, and especially with the combination of IFN-gamma and TNF-alpha. The maximal ICAM-1 expression on both epithelial cell types was obtained with the combination of TNF-alpha and IFN-gamma after 48 h of incubation. The NCI-H292 cell line was different in that it only showed increased ICAM-1 expression after stimulation with PMA and IFN-gamma and not by the combination of IFN-gamma and TNF-alpha or with TNF-alpha alone. In conclusion, the bronchial epithelial cells tested express several adhesion molecules, but only ICAM-1 expression was influenced by inflammatory cytokines.
Am J Respir Cell Mol Biol 1993 Dec
PMID:Expression and modulation of adhesion molecules on human bronchial epithelial cells. 750 27


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