Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00017 (IFN-gamma)
 28,919 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene expression of myeloperoxidase (MPO) in HL60 cells, as tested by Northern blot analysis with a MPO gene probe, was markedly suppressed by treatment with gamma interferon (IFN-gamma)(200U/ml) for 9hr, whereas cytochemically detected MPO activity, cell surface antigen expression, and cell morphology remained unchanged even at 48hr after the treatment. IFN-gamma of 50U/ml was sufficient for the suppression at 24hr. When the HL60 cells treated with IFN-gamma (200U/ml) for 24hr were cultured in the absence of IFN-gamma for another 24hr, the transcript of MPO gene reverted to a level comparable to that of the HL60 cells cultured thoroughly in the absence of IFN-gamma, indicating the reversibility of the suppression. The suppression of MPO expression at RNA level, possibly independent of differentiation, is one of the biological activities exerted by IFN-gamma, which has not been previously reported.
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PMID:[Suppression of myeloperoxidase gene expression by gamma-interferon]. 133 96

A monocytoid cell line (DOP-M1) was established from mononuclear cells separated from the cerebrospinal fluid of a 1-year-old girl with acute monoblastic leukemia (AMoL) (French-American-British; FAB-M5a). Judged by morphological, cytochemical, and immunological criteria, the DOP-M1 cells showed immature monocytoid characteristics. They were positive for alpha-naphthyl butyrate esterase, the expression of which was inhibited by NaF, and for myeloperoxidase (MPO). Positive MPO findings in nuclear envelope were detectable by electron microscopy. The cell surface was positive for CD15, CD33, and CDw65, but negative for CD4, CD14, and HLA-DR. HLA-DR expression was detected after treatment with IFN-gamma. Chromosome analysis of DOP-M1 cells revealed 47,X,-X,-13,+19,+20,+mar. Our established cell line, DOP-M1 appears to be a cell line which will be a useful tool for studying the phenotype, morphology, and function of monocytoid cells.
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PMID:Establishment of a monocytoid cell line (DOP-M1) from an infant with acute monocytic leukemia. 158 83

Ferric ammonium citrate (FAC) is nonmitogenic for human peripheral blood mononuclear cells (PBM) but has a potent mitogenic activity in the presence of IL-2. FAC in the presence of IL-2 increases the number of human peripheral blood mononuclear cells (PBM) expressing receptors for IL-2 and transferrin. FAC also markedly stimulates human PBM treated with supraoptimal, nonmitogenic concentrations of Con A. FAC, in the presence of IL-2, is a T-cell mitogen with a stringent requirement for macrophages. FAC stimulates the production of TNF-alpha and IFN-gamma in human PBM, and this effect is potentiated by IL-2. Thiourea and 3-amino-1,2,4-triazole selectively inhibit mitogenesis induced by FAC, indicating that oxygen radicals or peroxidase may mediate the triggering signal induced by this mitogen. In addition to hemin, as we have previously reported, and FAC, a variety of iron-containing proteins have lymphocyte stimulatory properties in combination with IL-2. They include horseradish peroxidase, cytochrome c, myoglobin, and transferrin. We have given the name ferro-mitogens to this group of compounds.
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PMID:Ferro-mitogens: iron-containing compounds with lymphocyte-stimulatory properties. 201 30

IFN-alpha and IFN-gamma were found to enhance monocyte-mediated activity by acting on both tumor cells and monocytes. The addition of IFN-alpha or IFN-gamma enhanced the monocyte-mediated cytotoxicity of the human melanoma cell line, A375, as well as the human colon carcinoma cell line, HT-29. However, IFN-alpha generally induced more monocyte-mediated lysis of the A375 cells, whereas IFN-gamma induced more monocyte-mediated lysis of the HT-29 cells. These differences are, in part, due to the direct effects of the IFN on the tumor cells. Pretreatment of A375 cells with either IFN-alpha or IFN-gamma significantly enhanced their susceptibility to lysis by untreated monocytes. However, only IFN-gamma pretreatment of HT-29 cells enhanced the lysis of these cells by untreated monocytes. Differences were also observed in the activation of monocytes by IFN-alpha vs IFN-gamma with respect to their ability to induce soluble cytotoxic factors. We found that the addition of IFN-gamma and tumor cells (either the A375 or HT-29 cells) to monocytes induced TNF release, whereas IFN-alpha or IFN-gamma alone or IFN-alpha and tumor cells had no effect. Despite its presence, TNF did not appear to play a major role in the killing of either tumor cell line. However, inhibitors of H2O2-myeloperoxidase system suppressed both IFN-alpha- and IFN-gamma-induced cytotoxicity of the HT-29 cells. Thus IFN-alpha and IFN-gamma can induce both similar and distinct mechanisms of cytotoxicity in monocytes. In addition, both IFN types can increase the susceptibility of tumor cells to lysis by untreated monocytes, although sensitivity to IFN-alpha vs IFN-gamma may vary with different tumor cell lines. These differences observed between IFN-alpha and IFN-gamma on monocytes and tumor cells could have important implications for the clinical use of these cytokines.
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PMID:IFN-alpha and IFN-gamma can affect both monocytes and tumor cells to modulate monocyte-mediated cytotoxicity. 215 15

We improved an ELISA bioassay for murine IFN-gamma (MuIFN-gamma) based on measurement of Ia antigen on P388D1, a mouse macrophagic tumour line. Cells were cultured in microtitre plates in medium containing dilutions of IFN-gamma source. They were then washed and stained with a rat anti-mouse I amAb followed by mouse anti-rat peroxidase-labelled antibody. After incubation with substrate, the OD was read directly from microtitre plates. Standard curves obtained with reference NIH MuIFN-gamma showed that this assay allowed for the definition of unit values (giving 50% of the maximal effect) comparable to NIH international units (IU). It detected as low as 0.2 IU/ml of MuIFN-gamma and, in contrast to antiviral assays, was insensitive to IFN-alpha/beta. We used a concanavalin A-conditioned supernatant, which is a mixed source of lymphokines, to assess the specificity of our assay. Indeed, Ia expression induced by ConA-conditioned supernatant was fully inhibited by preincubation with anti-MuIFN-gamma antibodies. Using a stable indicator cell line, the present cell surface assay is easier to perform than other ELISA using bone-marrow-derived macrophages, and does not require cell fixation; its high sensitivity and specificity are comparable to that of immunoradiometric assays. It is thus valuable for routine MuIFN-gamma quantitations in culture supernatant and biological fluids.
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PMID:Improvement of an ELISA bioassay for the routine titration of murine interferon-gamma. 250 15

A possible approach to the immunotherapy of tumors is to stimulate either specific or nonspecific immune responses in vivo. We recently found that provision of a mitogenic signal to PBMC, by incubation with the oxidizing mitogens, enhanced the effect of IL-2 in generating cytolytic activity. We therefore searched for a mitogen that might safely be administered to patients. The present study is an investigation of the mitogenic properties of iron and tin (Sn)-protoporphyrin and their capacity to induce cytotoxicity in human PBMC. These agents have been administered to humans with little toxicity. Both iron- (hemin) and Sn-protoporphyrin induce mitogenicity in peripheral T cells. This effect is markedly enhanced by low concentrations of IL-2. Hemin and Sn-protoporphyrin, in combination with IL-2, increase IL-2R on PBMC. Hemin alone, and to a greater extent in combination with IL-2, induces cytotoxicity for NK-sensitive and NK-resistant cell lines. Sn-protoporphyrin, a more potent mitogen than hemin, fails to induce cytotoxicity, and has a marked inhibitory effect on cytotoxicity induced by IL-2. Hemin and Sn-protoporphyrin stimulate TNF-alpha and IFN-gamma production by PBMC. IL-2 is synergistic with the metalloporphyrins in eliciting this effect. Metalloporphyrin-induced mitogenesis has a stringent requirement for macrophages. Scavengers of oxygen-free radicals and inhibitors of peroxidase inhibit mitogenicity induced by hemin but not that induced by Sn-protoporphyrin. Hence, an oxidative event may mediate the mitogenic effect of hemin. Our results indicate that hemin is an immunostimulatory agent in vitro and the data warrant further evaluation of its in vivo immunostimulatory and antitumor effect.
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PMID:Immune stimulatory properties of metalloporphyrins. 251 45

Using three different monoclonal antibodies (McAb no. 374, no. 964 and no. 1190) to human interleukin-1 alpha (rHu-IL-1 alpha), we have established two sandwich enzyme immunoassays (EIA) to differentiate rHu-IL-1 alpha and its deamidated derivative (rHu-Asp36-IL-1 alpha) where the asparagine at position 36 (counting from the N-terminus) of rHu-IL-1 alpha is converted to Asp. The McAb no. 1190 reacts specifically with rHu-IL-alpha and not with the rHu-Asp36-IL-1 alpha whereas both no. 374 and no. 964 can react with the two different forms of rHu-IL-1 alpha. The first EIA (S-EIA I) which uses the McAb no. 964 labelled with horse-radish peroxidase and the McAb no. 1190 fixed to the microtiter plate, only measure rHu-IL-1 alpha. The second EIA (S-EIA II) which uses enzyme labelled no. 964 and no. 374 fixed to the plate, can detect both rHu-IL-1 alpha and rHu-Asp36-IL-1 alpha and this assay of total rHu-IL-1 alpha is comparable to a competitive EIA using an enzyme-labelled rHu-IL-1 alpha and an anti-rHu-IL-1 alpha polyclonal antibody. Thus, the level of rHu-Asp36-IL-1 alpha in the samples containing the two IL-1 alpha s can be calculated by subtracting the level measured by S-EIA I from that measured by S-EIA II. The two EIA systems with an assay range of 1.5-100 ng/ml do not recognize IL-1 beta, IL-2, rHu-TNF alpha, IFN-alpha and IFN-gamma of human origin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential determination of recombinant human interleukin-1 alpha and its deamidated derivative by two sandwich enzyme immunoassays using monoclonal antibodies. Comparison with a polyclonal antibody-based competitive enzyme immunoassay. 265 27

Purified PGL-1 and dPGL from M. leprae can prevent bacterial killing by intact phagocytes and cell-free antimicrobial systems. Both glycolipids completely abolished the antimicrobial effect of the acetaldehyde-XO-Fe2+ system. Because the cytotoxicity of this system is inhibited by catalase, SOD, mannitol, and ethanol, but not by heated SOD or catalase, these data suggest that toxicity is due to OH. generated by the Haber-Weiss reaction. That the antimicrobial killing in the XO system is completely blocked by the addition of PGL-1 or dPGL suggests that these glycolipids can act as OH. scavengers. A modest protective effect against the cytotoxicity of the MPO-H2O2-halide system by both PGL-1 and dPGL was also observed. The antimicrobial activity of the MPO system was abolished with chloride, but not iodide, as the halide. The effect of the M. leprae-derived glycolipid on bacterial killing by intact phagocytes was examined. Two linking antibodies were used to bind the dPGL to a rapidly growing test organism, S. aureus, a murine IgM mAb specific for the terminal glycoside of PGL-1, and a rabbit IgG anti-mouse IgM which bound the staphylococcal protein A via its Fc region. Examination by transmission EM of human monocyte-derived macrophages which had ingested staphylococci either coated with both antibodies and dPGL, or coated only with the IgG and IgM antibodies, demonstrated the presence of bacteria in phagosomes of control and IFN-gamma-activated macrophages. Activation of the macrophage monolayers by pretreatment with IFN-gamma markedly increased their staphylocidal activity. When dPGL coated staphylococci were ingested, killing by both control and IFN-gamma-activated macrophages was completely blocked. These results, suggesting that PGL-1 can scavenge reactive oxygen species and prevent microbial death within the phagosome, may in part explain the intracellular survival of M. leprae in certain cell types.
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PMID:The effect of phenolic glycolipid-1 from Mycobacterium leprae on the antimicrobial activity of human macrophages. 282 38

rIL-4 (B cell stimulatory factor 1) induces the expression of Fc epsilon R2/CD23 on normal human monocytes (Mo). Fc epsilon R2/CD23 induction was detectable both by flow cytometry using anti-CD23 mAbs as well as soluble IgE, and by the immunoprecipitation with CD23-specific mAb or IgE of a 45-kD band from 125I-lactoperoxidase-labeled Mo. Fc epsilon R2/CD23 was fully expressed after a 24-h incubation with rIL-4, and was still detectable after 72 h from the addition of IL-4. This effect was specific, because none of the other rILs tested (IL-1, IL-2, IL-3, IL-5, B cell stimulatory factor 2, granulocyte-macrophage colony stimulating factor, and IFN-gamma) could induce FC epsilon R2/CD23, either alone or in various combinations. No synergism was observed between IL-4 and other ILs. IFN-gamma was not able to inhibit the IL-4-induced expression of Fc epsilon R2/CD23 on Mo, neither when added to the culture together with IL-4, nor when added 36 h earlier.
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PMID:Human recombinant interleukin 4 induces Fc epsilon R2/CD23 on normal human monocytes. 296 37

Monocytes lack lactoferrin and have much less myeloperoxidase than neutrophils. They also acquire a potential catalyst for .OH production (tartrate-resistant acid phosphatase) as they differentiate into macrophages. Consequently, the nature of free radicals produced by these cells was examined using the previously developed spin-trapping system. When stimulated with either PMA or OZ neither monocytes nor monocyte-derived macrophages (MDM) exhibited spin trap evidence of .OH formation. Pretreatment with IFN-gamma failed to induce MDM .OH production. When provided with an exogenous Fe+3 catalyst, both stimulated monocytes and MDM, but not PMN, exhibited sustained .OH production, presumably due to the absence of lactoferrin in mononuclear phagocytes. Sustained production of .OH could contribute to the microbicidal activity of mononuclear phagocytes as well as inflammatory tissue damage under in vivo conditions where catalytic Fe+3 may be present.
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PMID:Mononuclear phagocytes have the potential for sustained hydroxyl radical production. Use of spin-trapping techniques to investigate mononuclear phagocyte free radical production. 319 73


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