Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI

Article Abstract:

The effectiveness of the immune response determines whether the animal will live or die. One component of the immune response is the synthesis of cytokines, substances secreted by the cells of the immune system that fight invading substances. In some cases, the antibody-mediated response is most effective, while in others, a delayed-type hypersensitivity (DTH) response protects best. To investigate the relationship between the antibody response and DTH, researchers studied two mouse T cell (a type of white blood cell active in immune response) lines, TH2 and TH1. TH2 cells produce interleukin-4 and -5 (IL-4 and IL-5), which help B cell (antibody) responses. TH1 cells secrete IL-2 and interferon-gamma (IFN-g), induce DTH, and stimulate another component of the immune system, the macrophage. If, as seems possible from other evidence, the antibody response and DTH are mutually exclusive, then the products of these two cell types may inhibit one another. In fact, it is already known that IFN-g inhibits proliferation (multiplication) of TH2 cells, while proliferation of TH1 is inhibited by an unidentified product of TH2 cells. Cytokine synthesis inhibitory factor (CSIF, IL-10) is manufactured by TH2 cells and inhibits synthesis of IFN-g and other factors produced by TH1 cells. An investigation into the structure of the DNA (genetic material) that codes for CSIF was undertaken. It was found that CSIF DNA and the protein sequences it codes for, while not homologous (similar) to other cytokine genes or their protein products, were related to an open reading frame (a genetic sequence) called BCRFI in the Epstein-Barr virus (EBV) genome. This implies that BCRFI might represent an earlier version of the CSIF gene that was 'captured' by the virus. EBV infection is associated with impairment of both the antibody and DTH responses. IFN-g synthesis can be inhibited by CSIF and BCRFI, and IFN-g can inhibit the growth of EBV-infected B cells. Thus, perhaps the EBV 'uses' the product of the cytokine gene to weaken the immune system, enhancing its own survival. CSIF could also have a therapeutic role when suppression of TH1 immune responses is necessary, such as after transplantation. (Consumer Summary produced by Reliance Medical Information, Inc.)

Interleukins, Immune response, Epstein-Barr virus

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A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins

Article Abstract:

There are two types of tumor necrosis factors (TNFs), TNF-alpha and TNF-beta, which are produced by the cells of the immune system, specifically the macrophage and lymphocyte, respectively. TNFs are cytokines which have various effects on the immune and inflammatory response and on the killing of tumor cells and cells infected with viruses. TNF has an effect in the clinical conditions of chronic infection and cancer. The cellular receptors for TNF are present on all types of cells, except the reproductive cells, the egg and the sperm. The gene coding for a receptor which binds TNF has been isolated and characterized. The receptor was shown to be able to bind both the alpha and beta types of TNF. The portion of the protein which is on the outside of the cell, which binds TNF, is similar to five other proteins that have been previously identified, including the receptor which binds nerve growth factor, and a protein from Shope fibroma virus, a poxvirus that causes cancer in newborn rabbits. This group of related proteins defines a family of receptors which may have been derived from a single gene in the process of evolution. The isolation of the gene coding for the TNF receptor will allow the study of the mechanisms of how TNF causes the various cellular responses. Perhaps the receptor can be altered to manipulate the effect of TNF in various disease states. (Consumer Summary produced by Reliance Medical Information, Inc.)

Growth factors, Tumor necrosis factor

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The cholinergic neuronal differentiation factor from heart cells is identical to leukemia inhibitory factor

Article Abstract:

Cytokines are proteins that control the growth and differentiation (identity) of cells in various body tissues; both embryonic and adult tissues are influenced by the cytokines. Some cytokines, including interleukin-6, regulate bone marrow cells. Scientists have learned about cytokines by way of the genes that regulate their production. Once the gene for a certain protein is discovered, it is cloned (an exact copy is made), and using the clone the biological activities of the protein can be analyzed. A specific protein with many roles in the body is discussed. It has been given various names, including D factor, DIA, DRF and LIF (leukemia inhibitory factor). D factor is secreted by rat heart cells, but also regulates rat nerve cell differentiation. (D factor is the cholinergic neuronal differentiation factor.) In addition, it influences the bone marrow cells in the embryo, bone metabolism, and protein synthesis by liver cells. The D factor cytokine influences cell growth and differentiation in various tissues of the rat embryo and adult organism; the latest discovery is that D factor affects the nervous system.

Analysis, Embryology, Experimental, Embryological research, Growth regulators, Developmental neurology, Peptide regulatory factors

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