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  • Walter de Gruyter GmbH  (13)
  • Winkler, Christiana  (13)
  • 1
    Online Resource
    Online Resource
    Interferon-y-Induced Growth Inhibition of Neuroblastoma Cells is Independent of Induction of Nitric Oxide Synthase and Indoleamine 2,3-dioxygenase
    Walter de Gruyter GmbH ; 2004
    In:  pteridines Vol. 15, No. 3 ( 2004-08), p. 91-96
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 15, No. 3 ( 2004-08), p. 91-96
    Abstract: We investigated a possible involvement of nitric oxide formed by inducible nitric oxide synthase (iNOS) in the signaling cascade leading to growth inhibition and differentiation in the human neuroblastoma cell line SK-NSII. Treatment of SK-N-SH with interferon-γ (IFN-γ) plus interleukin-lß (IL-lß) led to induction of iNOS, growth inhibition and an altered cell shape. However two inhibitors of iNOS were not able to prevent cytokine induced changes. In addition, IFN-γ alone led to growth inhibition in absence of iNOS induction. Inhibition of the induced indoleamine 2,3-dioxygenase (IDO) activity also did not prevent growth inhibition. Our findings show that mechanisms other than NO and IDO can control interferon-y-induced growth inhibition of SK-N-SH cells.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2004.15.3.91
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2004
    detail.hit.zdb_id: 2279565-0
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  • 2
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    Neopterin suppresses the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase in human peripheral blood mononuclear cells
    Walter de Gruyter GmbH ; 2013
    In:  pteridines Vol. 24, No. 3-4 ( 2013-12-01), p. 237-243
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 24, No. 3-4 ( 2013-12-01), p. 237-243
    Abstract: In vitro , large amounts of neopterin are released from human monocyte-derived macrophages and dendritic cells primarily upon stimulation with Th1-type cytokine interferon-γ (IFN-γ). IFN-γ also induces the enzyme indoleamine 2,3-dioxygenase (IDO), which degrades tryptophan (TRP) to form kynurenine (KYN). IDO-mediated TRP catabolism is very effective in suppressing the proliferation of T lymphocytes as well as of pathogens in vitro and in vivo . In this study, we investigated whether exogenously added neopterin may influence IDO activity in resting and in stimulated peripheral blood mononuclear cells (PBMC). PBMC were isolated from healthy donors, and neopterin was added in a concentration range from 0.01 to 50 μmol/L. After 30 min, PBMC were stimulated or not with 10 μg/mL of mitogen phytohemagglutinin (PHA). After 48 h, culture supernatants were collected, KYN and TRP concentrations were measured by high-performance liquid chromatography, and the ratio of KYN vs. TRP was calculated as an estimate of IDO activity. Spontaneous as well as PHA-induced TRP breakdown was suppressed by exogenously added neopterin in a dose-dependent way; the lowest active concentration of neopterin was 〈 100 nmol/L. As neopterin concentrations in the nanomolar range are commonly observed in patients suffering from infections, sepsis, or uremia, our results suggest that neopterin formation might also serve as a feedback mechanism to slow down TRP degradation in vivo .
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pterid-2013-0037
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2013
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  • 3
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    Online Resource
    Serial Analysis of Tryptophan Degradation and Neopterin Formation in an otherwise Healthy Individual before and during an Infectious Episode
    Walter de Gruyter GmbH ; 2006
    In:  pteridines Vol. 17, No. 1 ( 2006-02), p. 25-30
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 17, No. 1 ( 2006-02), p. 25-30
    Abstract: Thl-type cytokine interferon-y induces neopterin production in human monocyte-derived macrophages and it stimulates enzyme indoleamine (2,3)-dioxygenase (IDO) which converts tryptophan to kynurenine in various cells. In an integrative single-case study, a healthy, 27-year-old female had collected her entire urine in 12-hour (= I lag) intervals on 56 consecutive days. Neopterin, tryptophan, kynurenine and Creatinine concentrations were determined using HPLC. The kynurenine to tryptophan ratio (kyn/trp) was calcuiated as an index for IDO activity. Within the Observation period, the woman experienced an infection episode presenting with vomiting and headache, however, not serologically verified. During this period, strong increases in both urinary kyn/trp and neopterin to Creatinine concentrations were observed, and thcrc was a significant correlation between neopterin/creatinine and kyn/trp at the same day (r s =0.334, p 〈 0.001). However, adjusted cross-correlational analysis revealed that accelerated tryptophan degradation preceded increases in neopterin by 24 to 36 hours (24h: r =0.185, 36h: r =0.408; both p 〈 0.05). Our Observation confirms the dose relationship between neopterin production and tryptophan degradation under real-life conditions.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2006.17.1.25
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2006
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  • 4
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    Follow-up of Urinary Neopterin Concentrations in two Healthy Children until Adolescence
    Walter de Gruyter GmbH ; 2003
    In:  pteridines Vol. 14, No. 3 ( 2003-08), p. 102-107
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 14, No. 3 ( 2003-08), p. 102-107
    Abstract: Neopterin is a sensitive marker of the activated cellular (= Thl-type) immune response. Neopterin concentrations in healthy children are higher compared with those of adults and are declining with increasing age. In this study, we present a follow-up of urinary neopterin to creatinine concentrations in two healthy children until adolescence. Data were available from one female (7 - 23 years) and her brother (0 - 18 years), of whom early morning urine specimens were collected on an irregular basis throughout 18 years. In total, neopterin and creatinine concentrations were measured by high pressure liquid chromatography (HPLC) in 343 urinary specimens. In both children, concentrations of urinary neopterin were highest at study entry. With increasing age neopterin concentrations decreased continuously to reach rather constant levels around the age of fifteen years. On several occasions at which individuals presented with common sickness, mostly of infectious origin, neopterin concentrations were found highly increased. In the absence of such infectious episodes, neopterin/creatinine measurements of both individuals fit well to previously established normal ranges. However this was true only for specimens collcctcd when children were older than 10 years, before that age concentrations of neopterin were frequently found to be higher than the established upper limits of the normal range.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2003.14.3.102
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2003
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  • 5
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    Online Resource
    Neopterin to Monitor Clinical Pathologies Involving Interferon-γ Production
    Walter de Gruyter GmbH ; 2004
    In:  pteridines Vol. 15, No. 3 ( 2004-08), p. 75-90
    Details
    In: pteridines, Walter de Gruyter GmbH, Vol. 15, No. 3 ( 2004-08), p. 75-90
    Abstract: Upon stimulation with the cytokine interferon-γ human monocytes/macrophages produce neopterin. Accordingly, measurement of neopterin concentrations in body fluids like blood, urine or cerebrospinal fluid provides information about activation of immune response involving type 1 Τ helper cells. Increased neopterin production is found in infections by viruses including human immunodeficiency virus (HIV), infections by intracellular living bacteria and parasites, autoimmune diseases, malignant tumor diseases and in allograft rejection episodes, but also in some neurodegenerative and in cardiovascular diseases. Major diagnostic applications of neopterin measurements are monitoring of the immune status of allograft recipients, detection of infectious diseases in blood donations and monitoring of therapy in HIV-infected individuals. Neopterin concentrations also provide prognostic information in HIV-infected individuals and in several malignant tumor diseases, high neopterin production at the moment of diagnosis is associated with poorer survival expectations. As high neopterin production is associated with increased production of reactive oxygen species and with low serum concentrations of antioxidants like α-tocopherol, neopterin can be regarded as a marker of oxidative stress caused by an activated immune system. Therefore, by neopterin measurements not only the extent of cellular immune activation, but also the extent of tissue damage caused by reactive oxygen specics may be estimated.
    Type of Medium: Online Resource
    ISSN: 2195-4720 , 0933-4807
    URL: Article
    DOI: 10.1515/pteridines.2004.15.3.75
    Language: English
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2004
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  • 6
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    Hyperhomocysteinemia and Immune Activation
    Walter de Gruyter GmbH ; 2003
    In:  Clinical Chemistry and Laboratory Medicine Vol. 41, No. 11 ( 2003-01-17)
    Details
    In: Clinical Chemistry and Laboratory Medicine, Walter de Gruyter GmbH, Vol. 41, No. 11 ( 2003-01-17)
    Type of Medium: Online Resource
    ISSN: 1434-6621
    URL: Article
    DOI: 10.1515/CCLM.2003.221
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2003
    detail.hit.zdb_id: 1492732-9
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  • 7
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    Atorvastatin suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells
    Walter de Gruyter GmbH ; 2005
    In:  Clinical Chemistry and Laboratory Medicine (CCLM) Vol. 43, No. 12 ( 2005-01-1)
    Details
    In: Clinical Chemistry and Laboratory Medicine (CCLM), Walter de Gruyter GmbH, Vol. 43, No. 12 ( 2005-01-1)
    Abstract: Hyperhomocysteinemia is regarded as an independent risk factor for vascular diseases, and homocysteine is supposed to contribute to oxidative stress and endothelial damage. Statin therapy is an established intervention to reduce the risk of acute events in patients suffering from cardiovascular diseases. Apart from their lipid-lowering capacity, statins also exert anti-inflammatory and antioxidant effects. As cellular immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular diseases, the anti-inflammatory capacity of statins could partly be responsible for the beneficial effects observed in patients. Earlier we reported that stimulated peripheral blood mononuclear cells (PBMCs) release homocysteine. Here we studied the influence of atorvastatin on homocysteine production in stimulated PBMCs and compared changes in cysteine concentrations and in neopterin production, which is a sensitive indicator of cellular immune activation. Stimulation of human PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significant homocysteine and neopterin production compared to unstimulated cells, whereas cysteine concentrations remained unchanged. Treatment of PBMCs with increasing doses of atorvastatin (10–100μM) suppressed both biochemical pathways in a dose-dependent manner, and cell proliferation was inhibited in parallel. Again, cysteine levels were not influenced by any treatment. The down-regulating effect of atorvastatin on homocysteine formation in vitro indicates that statins may prevent homocysteine accumulation in the blood via immunosuppression.
    Type of Medium: Online Resource
    ISSN: 1434-6621 , 1437-4331
    URL: Article
    DOI: 10.1515/CCLM.2005.234
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2005
    detail.hit.zdb_id: 1492732-9
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  • 8
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    Anti-inflammatory compound resveratrol suppresses homocysteine formation in stimulated human peripheral blood mononuclear cells in vitro
    Walter de Gruyter GmbH ; 2005
    In:  Clinical Chemistry and Laboratory Medicine (CCLM) Vol. 43, No. 10 ( 2005-01-1)
    Details
    In: Clinical Chemistry and Laboratory Medicine (CCLM), Walter de Gruyter GmbH, Vol. 43, No. 10 ( 2005-01-1)
    Abstract: Inflammation, immune activation and oxidative stress play a major role in the pathogenesis of cardiovascular disorders. In addition to markers of inflammation, moderate hyperhomocysteinemia is an independent risk factor for cardiovascular disease, and there is a link between the activation of immunocompetent cells and the enhanced formation of homocysteine in vitro. Likewise, anti-inflammatory drugs and nutrients rich in antioxidant vitamins are able to reduce cardiovascular risk and to slow down the atherogenic process. Resveratrol, a phenolic antioxidant synthesized in grapes and vegetables and present in wine, has also been supposed to be beneficial for the prevention of cardiovascular events. Apart from its strong antioxidant properties, resveratrol has also been demonstrated to act as an anti-inflammatory agent. In this study the influence of resveratrol on the production of homocysteine by stimulated human peripheral blood mononuclear cells (PBMCs) was investigated. Results were compared to earlier described effects of the anti-inflammatory compounds aspirin and salicylic acid and of the lipid-lowering drug atorvastatin. Stimulation of PBMCs with the mitogens concanavalin A and phytohemagglutinin induced significantly higher homocysteine accumulation in supernatants compared with unstimulated cells. Treatment with 10–100μM resveratrol suppressed homocysteine formation in a dose-dependent manner. Resveratrol did not influence the release of homocysteine from resting PBMCs. The data suggest that resveratrol may prevent homocysteine accumulation in the blood by suppressing immune activation cascades and the proliferation of mitogen-driven T-cells. The effect of resveratrol to down-regulate the release of homo-cysteine was comparable to the decline of neopterin concentrations in the same experiments. The suppressive effect of resveratrol was very similar to results obtained earlier with aspirin, salicylic acid and atorvastatin; however, it appeared that doses of compounds needed to reduce homocysteine levels to 50% of stimulated cells were always slightly lower than those necessary to achieve the same effect on neopterin concentrations. The influence of resveratrol and of all the other compounds on homocysteine production appears to be independent of any direct effect on homocysteine biochemistry.
    Type of Medium: Online Resource
    ISSN: 1434-6621 , 1437-4331
    URL: Article
    DOI: 10.1515/CCLM.2005.189
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2005
    detail.hit.zdb_id: 1492732-9
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  • 9
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    Hyperhomocysteinaemia and immune activation in patients with cancer
    Walter de Gruyter GmbH ; 2007
    In:  Clinical Chemical Laboratory Medicine Vol. 45, No. 1 ( 2007-01-01)
    Details
    In: Clinical Chemical Laboratory Medicine, Walter de Gruyter GmbH, Vol. 45, No. 1 ( 2007-01-01)
    Type of Medium: Online Resource
    ISSN: 1434-6621 , 1437-4331
    URL: Article
    DOI: 10.1515/CCLM.2007.012
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2007
    detail.hit.zdb_id: 1492732-9
    SSG: 15,3
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  • 10
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    St. John's wort (Hypericum perforatum) counteracts cytokine-induced tryptophan catabolism in vitro
    Walter de Gruyter GmbH ; 2004
    In:  Biological Chemistry Vol. 385, No. 12 ( 2004-12-01), p. 1197-1202
    Details
    In: Biological Chemistry, Walter de Gruyter GmbH, Vol. 385, No. 12 ( 2004-12-01), p. 1197-1202
    Abstract: St. John's wort ( Hypericum perforatum) is an ancient folk remedy that has antiviral and antibacterial properties. Anti-inflammatory effects of the plant have been described and the application of H. perforatum extract as an effective antidepressant is well established. In this study we assayed the effect of H. perforatum extract on cytokine-induced tryptophan degradation in human peripheral blood mononuclear cells. Simultaneously, changes in the production of the immune activation marker neopterin were monitored. Both these biochemical pathways are triggered by interferon-γ. Our results show that extracts of H. perforatum strongly down-regulate mitogen-mediated tryptophan degradation in a dose-dependent manner. This effect seems to be based on a suppressive activity of H. perforatum on activated immunocompetent cells, resulting in a diminished production of interferon-γ. In line with this finding, neopterin synthesis was strongly down-regulated by the plant extract. Our results suggest that the reduction of tryptophan degradation by H. perforatum might be important in the action of the plant as an antidepressant.
    Type of Medium: Online Resource
    ISSN: 1431-6730 , 1437-4315
    URL: Article
    DOI: 10.1515/BC.2004.155
    Language: Unknown
    Publisher: Walter de Gruyter GmbH
    Publication Date: 2004
    detail.hit.zdb_id: 1466062-3
    SSG: 12
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