Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The interferon-inducible gene (IFI-78K gene) that codes for a human protein, p78, of 78,000 Mr is the equivalent of the mouse Mx gene encoding Mx protein. The IFI-78K gene is located on chromosome 21 together with the alpha/beta interferon (IFN-alpha/beta) receptor. The p78 protein is important since it may be involved in resistance to influenza viruses. The regulation of the IFI-78K gene was studied in human diploid cells by using a cDNA probe to p78 mRNA and specific monoclonal antibodies to p78 protein. The IFI-78K gene, a normally quiescent gene, is transcriptionally regulated by IFN-alpha, and its induction does not require protein synthesis. The rate of transcription measured in a run-on assay increased rapidly but transiently. The level of p78 mRNA increased up to 8 h, declining slowly afterwards. The p78 protein, undetectable in untreated cells, accumulated up to 16 h, and its amount remained stable for at least 36 h after the addition of IFN-alpha. Cytokines such as tumor necrosis factor, interleukin-1 alpha, and interleukin-1 beta activated the IFI-78K gene at concentrations comparable to that of IFN-alpha. However, gene activation by these cytokines required protein synthesis. Poly(rI)-poly(rC) induced the IFI-78K gene directly at the transcriptional level without requirement for protein synthesis. Newcastle disease virus, influenza virus, and to a lesser extent vesicular stomatitis virus also induced the IFI-78K gene in the absence of any protein synthesis. Induction of transcription by viruses was markedly enhanced by pretreatment of cells with IFN-gamma (which by itself is a poor inducer of the IFI-78K gene), resulting in accumulation of p78 protein during the course of infection; this suggests that IFN-gamma programs cells to full antiviral activity upon virus infection.
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PMID:Regulation of the interferon-inducible IFI-78K gene, the human equivalent of the murine Mx gene, by interferons, double-stranded RNA, certain cytokines, and viruses. 254 74

The abilities of Escherichia coli-derived human interferon gamma (IFN-gamma) and E. coli-derived human interferon-alpha A (IFN-alpha A) or -alpha 2 (IFN-alpha 2) to augment natural killer (NK) cytotoxicity were compared. When low concentrations (less than 10 antiviral units/ml) of interferons were used, and equal numbers of antiviral units of E. coli-derived IFN-gamma and E. coli-derived IFN-alpha A or IFN-alpha 2 were compared for their ability to augment NK, E. coli-derived IFN-gamma was found to be more active in augmenting NK against the K562 targets, than E. coli-derived IFN-alpha A or IFN-alpha 2. Antiviral units in these experiments were determined by the standard cytopathic effect assay using vesicular stomatitis virus (VSV)-challenged human fibroblasts, trisomic for chromosome 21. However, when these interferons were compared on a weight basis (ng/ml) or on a molar basis, their ability to augment NK against the K562 targets was comparable. These differences in the relative abilities of these interferons (when their concentrations were expressed in antiviral units/ml) to augment NK, were due to an approximately 100-fold difference in their specific activities (antiviral units per mg of interferon). These were 1.8 X 10(6) units/mg for E. coli-derived IFN-gamma, 2.0 X 10(8) units/mg for E. coli-derived IFN-alpha A, and 1.8 X 10(8) units/mg for E. coli-derived IFN-alpha 2. At concentrations higher than 10 units/ml, all these interferons showed a similar ability to augment NK. Studies on the kinetics of the augmentation revealed that in vitro treatment with E. coli-derived IFN-gamma for several hours was necessary for augmentation of NK against targets from haemopoietic human tumour cell lines (K562, Daudi). In contrast, alpha interferons were able to augment NK after treatment in vitro for significantly shorter periods (30 min or less with certain donors). Augmentation of NK cytotoxicity of human peripheral blood mononuclear leucocytes by E. coli-derived IFN-gamma was not accompanied by the induction of interleukin 2 (IL-2) production, suggesting that IL-2 is not involved in the augmentation of NK by IFN-gamma. A monoclonal antibody specific for human IFN-gamma blocked augmentation of NK by E. coli-derived IFN-gamma and natural IFN-gamma, but not by E. coli-derived IFN-alpha A or staphylococcal enterotoxin A (SEA).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Regulation of natural killer cytotoxicity by Escherichia coli-derived human interferon gamma. 308 22

The previously cloned human interferon alpha/beta (Hu-IFN-alpha/beta; Type I interferon) receptor cDNA appears to be only one component of a receptor complex since expression of the cDNA in mouse cells confers sensitivity only to Hu-IFN-alpha B2, but a monoclonal antibody against this cloned receptor subunit inhibits biological activities of Hu-IFN-alpha A, Hu-IFN-alpha B2, Hu-IFN-omega, and Hu-IFN-beta. Here we report that a yeast artificial chromosome (YAC) containing a segment of human chromosome 21 introduced into Chinese hamster ovary (CHO) cells confers upon these cells a greatly enhanced response to Hu-IFN-alpha A and Hu-IFN-alpha B2 as well as an increased response to Hu-IFN-omega, Hu-IFN-alpha A/D(Bgl), andd Hu-IFN-beta. These responses were measured by induction of class I MHC antigens and by protection against encephalomyocarditis virus and vesicular stomatitis virus. Furthermore, these cells exhibit specific high affinity binding of Hu-IFN-alpha A and Hu-IFN-alpha B2, Hu-IFN-beta, and Hu-IFN-omega. The results indicate that all the genes necessary to reconstitute a biologically active Type I human IFN receptor complex are located within the human DNA insert of this YAC clone.
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PMID:Expression of a functional human type I interferon receptor in hamster cells: application of functional yeast artificial chromosome (YAC) screening. 802 72