Immune Interferons Gene expressing

The immune interferon gene has been isolated, sequenced, and expressed.20 One approach for studying the biological activity of immune interferon is to change the amino acid... 

Cassatella, M. A., Hartman, L., Perussia, B., Trinchieri, G. (1989). Tumor necrosis factor and immune interferon synergistically induce cytochrome b.245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells. J. Clin. Invest. 83,1570-9. 

In eukaryotes, such as Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, and Oryza sativa, seven different a and seven different /8 genes have been found (Hughes, 1997 Bouzat et al., 2000 Sassa et al., 2000). In higher eukaryotes with an adaptive immune system, y-interferon stimulates expression of three additional /8-type subunits, which can replace the closely related, constitutively expressed active /8-type subunits (Rock and Goldberg, 1999 Rechsteiner et al., 2000). 

Lapinet, J. A., Scapini, P., Calzetti, F., Perez, O., and Cassatella, M. A. (2000). Gene expression and production of tumor necrosis factor alpha, interleukin-1 beta (IL-lbeta), IL-8, macrophage inflammatory protein lalpha (MIP-lalpha), MIP-lbeta, and gamma interferon-inducible protein 10 by human neutrophils stimulated with group B meningococcal outer membrane vesicles. Infect. Immun. 68, 6917-6923. 

Moreover, monomers and dimers were shown to repress NO production, TNF alpha secretion, and NF-kB-dependent gene expression induced by interferon y, whereas the trimeric procyanidin C2 and Pycnogenol enhanced these parameters. In addition, in unstimulated RAW 264.7 macrophages, both procyanidin C2 and Pycnogenol increased TNF gamma secretion in a concentration and time-dependent manner. These results demonstrate that procyanidins act as modulators of the immune response in macrophages [105]. 

A recent report has demonstrated that the proteolytic activity of NS3 plays an additional role in viral infection, beyond polyprotein processing. An important mediator of the cellular immune response is the transcription factor interferon regulatory factor 3 (IRF-3), which becomes activated on infection and then stimulates production of type-1 interferon and other antiviral genes [46]. It was found that expression of heterodimeric NS3/4A... 

Corticosteroids suppress both humoral and cellular immunity. Single doses produce a redistribution of lymphocytes with a concentration dependent decrease of CD4 and CDS positive cells. This in vivo lymphopenic effect correlates with the in vitro inhibition of stimulated T-cell proliferation. Furthermore, corticosteroids are able to inhibit the expression of genes coding for IL-1, IL-2, IL-6, interferon a, and tumor necrosis factor, TNE-a. Chronic administration decreases the size and also the cellu-larity of lymphoid tissues like lymph nodes, spleen, and thymus. Corticosteroids have more effect on the primary immune response and are less effective against previously sensitized immune responses. Their suppressive effects are more pronounced for T-cell immune responses than for the humoral immune response. 

The transcription activator NF B regulates a variety of genes involved in the immune response and the inflamatory process. NF B is required for the expression of genes for the light x-chain of immimoglobulins, interleukin 2 and 6, as well as for interferon b (see chapter 11). 

S. Brown,W.N. Rom, and M.D. Weiden. 2004. Aerosolized gamma interferon (IFN-gamma) induces expression of the genes encoding the IFN-gamma-induci-ble 10-kilodalton protein but not inducible nitric oxide synthase in the lung during tuberculosis. Infect. Immun. 72 1275-1283. 

Proteins are also used clinically to treat a variety of diseases. Erythropoietin stimulates erythrocyte production in kidney dialysis and chemotherapy patients. Granulocyte stimulating factor enhances immune systems compromised by cancer treatments. Cytokines such as interferons and interleukins are used for their anti-viral and anti-tumor activities. Other proteins are used to inhibit or stimulate blood clotting. For the most part, the pharmaceutical protein industry relies on cloning native human genes and expressing and purifying their products in recombinant form. 

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