Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017636 (glioblastoma)
 18,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant interferon-gamma (IFN-gamma) is a potent immune regulatory cytokine and is involved in the defense against several intracellular organisms, such as Chlamydia and Toxoplasma. Furthermore IFN-gamma is able to inhibit the growth of human tumor cell lines. The ability to inhibit the growth of intracellular organisms makes the therapeutic use of recombinant human IFN-gamma in certain patient groups, such as those with chronic granulomatous disease, leprosy, and HIV infection, very attractive. We have shown recently that IFN-gamma-mediated effects can be blocked by heparin and that this inhibitory effect can be abrogated by the addition of protamine. In this report, we show that the antagonistic effect of protamine on heparin-mediated inhibition of IFN-gamma activity is mainly due to the capacity of protamine to enhance IFN-gamma activity. We found that protamine enhances the capacity of IFN-gamma to inhibit the growth of different brain tumor cell lines, to induce indolamine 2, 3-dioxygenase activity, to induce toxoplasmostasis, and to induce MHC class II antigen expression in human glioblastoma cells and in human native fibroblasts. We were able to demonstrate that IFN-gamma binds to protamine, and, therefore, we assume that the effect of protamine on IFN-gamma is due to a direct interaction between the two molecules.
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PMID:Protamine enhances the activity of human recombinant interferon-gamma. 883 19

Induction of indoleamine 2,3-dioxygenase (IDO) by IFN-gamma results in growth inhibition of Toxoplasma and Chlamydia spp. as well as tumor cells. This is caused by the degradation, and therefore depletion, of L-tryptophan necessary for cell protein synthesis. Human macrophages stimulated with IFN-gamma express IDO and inhibit the growth of intracellular toxoplasma and chlamydia as well as that of extracellular bacteria such as group B streptococci. Here we describe experiments in which the L-tryptophan analog, 6-chloro-DL-tryptophan (CDLT) caused a dose-dependent inhibition in the IFN-gamma-induced IDO-mediated L-tryptophan degradation in monocyte-derived macrophages and glioblastoma cells. An inhibition of IDO activity of up to 80 % was observed at concentrations of CDLT of 750 microM. Expression of IDO at this concentration, as shown by Northern blot analysis, was unimpaired. This inhibition of IDO was coupled in glioblastoma cells by a complete abrogation of the IFN-gamma-induced toxoplasmastasis in these cells. IDO inhibition by CDLT in human macrophages resulted in a complete abrogation of the IFN-gamma-induced growth inhibition of streptococci and staphylococci. In contrast to this, IFN-gamma-induced toxoplasmastasis was not inhibited in human macrophages by CDLT-mediated IDO inhibition.
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PMID:Inhibition of indoleamine 2,3-dioxygenase in human macrophages inhibits interferon-gamma-induced bacteriostasis but does not abrogate toxoplasmastasis. 1054 Mar 37

Stimulation of human monocyte-derived-macrophages (MDM) with interferon gamma induces the L-tryptophan degrading enzyme indoleamine 2,3-dioxygenase (IDO). It has been well documented that the growth of some intra-cellular parasites such as Chlamydia and Toxoplasma in human fibroblasts and glioblastoma cells is inhibited by IDO mediated L-tryptophan depletion. We have recently shown that IDO induction in cord blood MDM is also responsible for the growth inhibition of extra-cellular group B streptococci and thus for the first time shown an anti-bacterial effect of IDO activation. In view of this immunological function we sought to investigate the regulation, and in particular the downregulation of IDO by the immune system. We describe here the effect of cytokines on IDO activation and in particular the inhibitory function of IL-10, TGF beta and IL-4.
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PMID:Cytokine mediated regulation of interferon-gamma-induced IDO activation. 1072 Oct 97