6 results on '"Pahl HL"'
Search Results
2. Volatile anesthetics induce caspase-dependent, mitochondria-mediated apoptosis in human T lymphocytes in vitro.
- Author
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Loop T, Dovi-Akue D, Frick M, Roesslein M, Egger L, Humar M, Hoetzel A, Schmidt R, Borner C, Pahl HL, Geiger KK, Pannen BHJ, Loop, Torsten, Dovi-Akue, David, Frick, Michael, Roesslein, Martin, Egger, Lotti, Humar, Matjaz, Hoetzel, Alexander, and Schmidt, Rene
- Published
- 2005
3. Sevoflurane inhibits phorbol-myristate-acetate-induced activator protein-1 activation in human T lymphocytes in vitro: potential role of the p38-stress kinase pathway.
- Author
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Loop T, Scheiermann P, Doviakue D, Musshoff F, Humar M, Roesslein M, Hoetzel A, Schmidt R, Madea B, Geiger KK, Pahl HL, and Pannen BH
- Subjects
- Blotting, Western, CD3 Complex genetics, Cytokines biosynthesis, Desflurane, Electrophoretic Mobility Shift Assay, Humans, Indicators and Reagents, Isoflurane pharmacology, Jurkat Cells, Luciferases genetics, Mitogen-Activated Protein Kinase 8, NF-kappa B metabolism, Phosphorylation, Protein Binding, Sevoflurane, Stress, Physiological physiopathology, T-Lymphocytes drug effects, Tetradecanoylphorbol Acetate pharmacology, Transcription Factor AP-1 genetics, Transfection, p38 Mitogen-Activated Protein Kinases, Anesthetics, Inhalation pharmacology, Isoflurane analogs & derivatives, Methyl Ethers pharmacology, Mitogen-Activated Protein Kinases metabolism, Signal Transduction drug effects, T-Lymphocytes metabolism, Tetradecanoylphorbol Acetate antagonists & inhibitors, Transcription Factor AP-1 metabolism
- Abstract
Background: Modulation of immune defense mechanisms by volatile anesthetics during general anesthesia may compromise postoperative immune competence and healing reactions and affect the infection rate and the rate of tumor metastases disseminated during surgery. Several mechanisms have been suggested to account for these effects. The current study was undertaken to examine the molecular mechanisms underlying these observations., Methods: Effects of sevoflurane, isoflurane, and desflurane were studied in vitro in primary human CD3 T-lymphocytes. DNA-binding activity of the transcription factor activator protein-1 (AP-1) was assessed using an electrophoretic mobility shift assay. Phorbol-myristate-acetate-dependent effects of sevoflurane on the phosphorylation of the mitogen-activated protein kinases were studied using Western blots, the trans-activating potency of AP-1 was determined using reporter gene assays, and the cytokine release was measured using enzyme-linked immunosorbent assays., Results: Sevoflurane inhibited activation of the transcription factor AP-1. This effect was specific, as the activity of nuclear factor kappabeta, nuclear factor of activated T cells, and specific protein-1 was not altered and several other volatile anesthetics studied did not affect AP-1 activation. Sevoflurane-mediated suppression of AP-1 could be observed in primary CD3 lymphocytes from healthy volunteers, was time-dependent and concentration-dependent, and occurred at concentrations that are clinically achieved. It resulted in an inhibition of AP-1-driven reporter gene activity and of the expression of the AP-1 target gene interleukin-3. Suppression of AP-1 was associated with altered phosphorylation of p38 mitogen-activated protein kinases., Conclusion: The data demonstrate that sevoflurane is a specific inhibitor of AP-1 and may thus provide a molecular mechanism for the antiinflammatory effects associated with sevoflurane administration.
- Published
- 2004
- Full Text
- View/download PDF
4. Thiopental inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappaB through suppression of kappaB kinase activity.
- Author
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Loop T, Humar M, Pischke S, Hoetzel A, Schmidt R, Pahl HL, Geiger KK, and Pannen BH
- Subjects
- Blotting, Western, CD3 Complex metabolism, Cell-Free System, Dithiothreitol pharmacology, Electrophoretic Mobility Shift Assay, Humans, I-kappa B Kinase, Indicators and Reagents, Jurkat Cells, Phosphorylation, Receptors, GABA drug effects, Signal Transduction drug effects, Structure-Activity Relationship, T-Lymphocytes drug effects, Thiobarbiturates pharmacology, Anesthetics, Intravenous pharmacology, Enzyme Inhibitors pharmacology, NF-kappa B antagonists & inhibitors, Protein Serine-Threonine Kinases antagonists & inhibitors, Thiopental pharmacology, Tumor Necrosis Factor-alpha antagonists & inhibitors, Tumor Necrosis Factor-alpha pharmacology
- Abstract
Background: Thiopental is frequently used for the treatment of intracranial hypertension after severe head injury and is associated with immunosuppressive effects. The authors have recently reported that thiopental inhibits activation of nuclear factor (NF) kappaB, a transcription factor implicated in the expression of many inflammatory genes. Thus, it was the aim of the current study to examine the molecular mechanism of this inhibitory effect., Methods: The authors tested gamma-aminobutyric acid (GABA), the GABA(A) antagonist bicuculline, and the GABA(B) antagonist dichlorophenyl-methyl-amino-propyl-diethoxymethyl-phosphinic acid (CGP 52432) in combination with thiopental for their influence on the activation of NF-kappaB. In addition, they investigated the direct effect of thiopental on activated NF-kappaB DNA binding activity. These experiments were conducted in Jurkat T lymphocytes using electrophoretic mobility shift assays. The presence of the phosphorylated and dephosphorylated NF-kappaB inhibitor IkappaBalpha (Western blotting) and IkappaB kinase activity were studied in Jurkat T cells and human CD3+ T lymphocytes. In addition, the authors tested the effect of the structural barbiturate analog pairs thiopental-pentobarbital and thiamylal-secobarbital and of thiopental in combination with the thio-group containing chemical dithiothreitol on the activation of NF-kappaB., Results: GABA did not inhibit NF-kappaB activation, and the GABA(A) and GABA(B) antagonists bicuculline and CGP did not diminish the thiopental-mediated inhibitory effect on NF-kappaB activation. Thiopental did not inhibit activated NF-kappaB directly in a cell-free system. The phosphorylation of IkappaBalpha was prevented after incubation with 1,000 microg/ml thiopental. The same concentration of thiopental also inhibited IkappaB kinase activity in tumor necrosis factor-stimulated Jurkat T cells and human CD3+ T lymphocytes (60% suppression, P < 0.05 vs. tumor necrosis factor alpha alone). Thiobarbiturates (4 x 10(-3) m) inhibited NF-kappaB activity, whereas equimolar concentrations of the structural oxyanalogs did not. Preincubation of thiopental with dithiothreitol diminished the inhibitory effect., Conclusion: Thiopental-mediated inhibition of NF-kappaB activation is due to the suppression of IkappaB kinase activity and depends at least in part on the thio-group of the barbiturate molecule.
- Published
- 2003
- Full Text
- View/download PDF
5. Differential effects of volatile anesthetics on hepatic heme oxygenase-1 expression in the rat.
- Author
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Hoetzel A, Geiger S, Loop T, Welle A, Schmidt R, Humar M, Pahl HL, Geiger KK, and Pannen BH
- Subjects
- Animals, Blood Pressure, Gene Expression Regulation, Enzymologic drug effects, HSP27 Heat-Shock Proteins, HSP70 Heat-Shock Proteins genetics, Heme Oxygenase-1, Liver drug effects, Male, Neoplasm Proteins genetics, RNA, Messenger analysis, Rats, Rats, Sprague-Dawley, Anesthetics, Inhalation pharmacology, Heat-Shock Proteins, Heme Oxygenase (Decyclizing) genetics, Liver enzymology
- Published
- 2002
- Full Text
- View/download PDF
6. Thiopental inhibits the activation of nuclear factor kappaB.
- Author
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Loop T, Liu Z, Humar M, Hoetzel A, Benzing A, Pahl HL, Geiger KK, and J Pannen BH
- Subjects
- Biotransformation drug effects, Blotting, Western, Cytokines metabolism, Electrophoresis, Genes, Reporter genetics, Humans, Indicators and Reagents, Jurkat Cells, Lymphocyte Activation drug effects, Monocytes drug effects, Monocytes metabolism, T-Lymphocytes drug effects, T-Lymphocytes metabolism, Hypnotics and Sedatives pharmacology, NF-kappa B antagonists & inhibitors, Thiopental pharmacology
- Abstract
Background: Thiopental is frequently used for the treatment of intracranial hypertension after severe head injury. Its long-term administration increases the incidence of nosocomial infections, which contributes to the high mortality rate of these patients. However, the mechanism of its immunosuppressing effect remains unknown., Methods: The effect of thiopental (200-1000 microg/ml) on the activation of the nuclear transcription factor kappaB (NF-kappaB; electrophoretic mobility shift assays), on NF-kappaB-driven reporter gene activity (transient transfection assays), on the expression of NF-kappaB target genes (enzyme-linked immunoassays), on T-cell activation (flow cytometric analyses of CD69 expression), and on the content of the NF-kappaB inhibitor IkappaB-alpha (Western blotting) was studied in human T lymphocytes in vitro., Results: Thiopental inhibited the activation of the transcription factor NF-kappaB but did not alter the activity of the cyclic adenosine monophosphate response element binding protein. Other barbiturates (methohexital), anesthetics (etomidate, propofol, ketamine), or opioids (fentanyl, morphine) did not affect NF-kappaB activation. Thiopental-mediated suppression of NF-kappaB could be observed in Jurkat cells and in primary CD3+ lymphocytes from healthy volunteers, was time- and concentration-dependent, occurred at concentrations that are clinically achieved, and persisted for hours after the incubation. It was associated with an inhibition of NF-kappaB-driven reporter gene activity, of the expression of interleukin-2, -6, and -8, and interferon gamma, and of the activation of CD3+ lymphocytes. Suppression of NF-kappaB appeared to involve reduced degradation of IkappaB-alpha., Conclusion: The results demonstrate that thiopental inhibits the activation of NF-kappaB and may thus provide a molecular mechanism for some of the immunosuppressing effects associated with thiopental therapy.
- Published
- 2002
- Full Text
- View/download PDF
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