Latest Publications

@article{prochazkova_adaptive_2018,

title = {Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands.},

author = {Jiřina Procházková and Simona Strapáčová and Lucie Svržková and Zdeněk Andrysík and Martina Hýžďalová and Eva Hrubá and Kateřina Pěnčíková and Helena Líbalová and Jan Topinka and Jiří Kléma and Joaquín M. Espinosa and Jan Vondráček and Miroslav Machala},

doi = {10.1016/j.toxlet.2018.04.024},

issn = {1879-3169 0378-4274},

year  = {2018},

date = {2018-08-01},

journal = {Toxicology letters},

volume = {292},

pages = {162–174},

abstract = {Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants.},

note = {Place: Netherlands},

keywords = {A549 Cells, Aryl hydrocarbon receptor, Aryl Hydrocarbon/*agonists/metabolism, Azo Compounds/toxicity, Basic Helix-Loop-Helix Transcription Factors/*agonists/metabolism, Benzo(a)pyrene/toxicity, Carbazoles/toxicity, Dioxins, Environmental Pollutants/*toxicity, Fluorenes/toxicity, Gene Expression Profiling/methods, Gene Expression Regulation, Gene Regulatory Networks/drug effects, Genetic/drug effects, Global gene expression profiling, Humans, Indoles/toxicity, Ligands, Lung cancer, Lung Neoplasms/*genetics/metabolism, Neoplastic/*drug effects, Oligonucleotide Array Sequence Analysis, Polychlorinated Dibenzodioxins/toxicity, Pyrazoles/toxicity, Receptors, Signal Transduction/drug effects, Thiazoles/toxicity, Time Factors, Transcription, Transcriptional Activation/drug effects, Transcriptome/*drug effects},

pubstate = {published},

tppubtype = {article}

}

@article{svobodova_aryl_2015,

title = {The aryl hydrocarbon receptor-dependent disruption of contact inhibition in rat liver WB-F344 epithelial cells is linked with induction of survivin, but not with inhibition of apoptosis.},

author = {Jana Svobodová and Markéta Kabátková and Lenka Šmerdová and Petra Brenerová and Zdeněk Dvořák and Miroslav Machala and Jan Vondráček},

doi = {10.1016/j.tox.2015.04.001},

issn = {1879-3185 0300-483X},

year  = {2015},

date = {2015-07-01},

journal = {Toxicology},

volume = {333},

pages = {37–44},

abstract = {Inhibition of apoptosis by the ligands of the aryl hydrocarbon receptor (AhR) has been proposed to play a role in their tumor promoting effects on liver parenchymal cells. However, little is presently known about the impact of toxic AhR ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on apoptosis in other liver cell types, such as in liver epithelial/progenitor cells. In the present study, we focused on the effects of TCDD on apoptosis regulation in a model of liver progenitor cells, rat WB-F344 cell line, during the TCDD-elicited release from contact inhibition. The stimulation of cell proliferation in this cell line was associated with deregulated expression of a number of genes known to be under transcriptional control of the Hippo signaling pathway, a principal regulatory pathway involved in contact inhibition of cell proliferation. Interestingly, we found that mRNA and protein levels of survivin, a known Hippo target, which plays a role both in cell division and inhibition of apoptosis, were significantly up-regulated in rat liver epithelial cell model, as well as in undifferentiated human liver HepaRG cells. Using the short interfering RNA-mediated knockdown, we confirmed that survivin plays a central role in cell division of WB-F344 cells. When evaluating the effects of TCDD on apoptosis induction by camptothecin, a genotoxic topoisomerase I inhibitor, we observed that the pre-treatment of WB-F344 cells with TCDD increased number of cells with apoptotic nuclear morphology, and it potentiated cleavage of both caspase-3 and poly(ADP-ribose) polymerase I. This indicated that despite the observed up-regulation of survivin, apoptosis induced by the genotoxin was potentiated in the model of rat liver progenitor cells. The present results indicate that, unlike in hepatocytes, AhR agonists may not prevent induction of apoptosis elicited by DNA-damaging agents in a model of rat liver progenitor cells.},

note = {Place: Ireland},

keywords = {AhR, Animals, Apoptosis, Apoptosis/*drug effects, Aryl Hydrocarbon/*agonists/metabolism, Basic Helix-Loop-Helix Transcription Factors/*agonists/metabolism, BIRC5/survivin, Camptothecin/*toxicity, Caspase 3/metabolism, Cell Line, Contact inhibition, Contact Inhibition/*drug effects, Epithelial Cells/*drug effects/metabolism/pathology, Genetic/drug effects, Hippo signaling, Humans, Inbred F344, Inhibitor of Apoptosis Proteins/genetics/metabolism, Liver/*drug effects/metabolism/pathology, Microtubule-Associated Proteins/genetics/*metabolism, Poly (ADP-Ribose) Polymerase-1, Poly(ADP-ribose) Polymerases/metabolism, Polychlorinated Dibenzodioxins/*toxicity, Rats, Receptors, RNA Interference, Signal Transduction/drug effects, Survivin, TCDD, Time Factors, Topoisomerase I Inhibitors/*toxicity, Transcription, Transfection, Up-Regulation},

pubstate = {published},

tppubtype = {article}

}

@article{kabatkova_interactive_2015,

title = {Interactive effects of inflammatory cytokine and abundant low-molecular-weight PAHs on inhibition of gap junctional intercellular communication, disruption of cell proliferation control, and the AhR-dependent transcription.},

author = {Markéta Kabátková and Jana Svobodová and Kateřina Pěnčíková and Dilshad Shaik Mohatad and Lenka Šmerdová and Alois Kozubík and Miroslav Machala and Jan Vondráček},

doi = {10.1016/j.toxlet.2014.09.023},

issn = {1879-3169 0378-4274},

year  = {2015},

date = {2015-01-01},

journal = {Toxicology letters},

volume = {232},

number = {1},

pages = {113–121},

abstract = {Polycyclic aromatic hydrocarbons (PAHs) with lower molecular weight exhibit lesser genotoxicity and carcinogenicity than highly carcinogenic PAHs with a higher number of benzene rings. Nevertheless, they elicit specific effects linked with tumor promotion, such as acute inhibition of gap junctional intercellular communication (GJIC). Although inflammatory reaction may alter bioactivation and toxicity of carcinogenic PAHs, little is known about the impact of pro-inflammatory cytokines on toxic effects of the low-molecular-weight PAHs. Here, we investigated the impact of a pro-inflammatory cytokine, tumor necrosis factor-α (TNF-α), on the effects associated with tumor promotion and with induction of the aryl hydrocarbon receptor (AhR)-dependent gene expression in rat liver epithelial cells. We found that a prolonged incubation with TNF-α induced a down-regulation of GJIC, associated with reduced expression of connexin 43 (Cx43), a major connexin isoform found in liver epithelial cells. The Cx43 down-regulation was partly mediated by the activity of the mitogen-activated protein (MAP) p38 kinase. Independently of GJIC modulation, or p38 activation, TNF-α potentiated the AhR-dependent proliferative effect of a model low-molecular-weight PAH, fluoranthene, on contact-inhibited cells. In contrast, this pro-inflammatory cytokine repressed the fluoranthene-induced expression of a majority of model AhR gene targets, such as Cyp1a1, Ahrr or Tiparp. The results of the present study indicate that inflammatory reaction may differentially modulate various toxic effects of low-molecular-weight PAHs; the exposure to pro-inflammatory cytokines may both strengthen (inhibition of GJIC, disruption of contact inhibition) and repress (expression of a majority of AhR-dependent genes) their impact on toxic endpoints associated with carcinogenesis.},

note = {Place: Netherlands},

keywords = {Animals, Aryl hydrocarbon receptor, Aryl Hydrocarbon/*agonists/genetics/metabolism, Basic Helix-Loop-Helix Transcription Factors/*agonists/genetics/metabolism, Cell Communication/*drug effects, Cell Line, Cell Proliferation, Cell Proliferation/*drug effects, Cell Transformation, Connexin 43/genetics/metabolism, Dose-Response Relationship, Drug, Enzyme Activation, Epithelial Cells/*drug effects/metabolism/pathology, Fluorenes/*toxicity, Gap junctions, Gap Junctions/*drug effects/metabolism/pathology, Gene Expression Regulation/drug effects, Genetic/*drug effects, Inflammation, Inflammation/chemically induced/genetics/metabolism/pathology, Liver Neoplasms/chemically induced/metabolism/pathology, Liver/*drug effects/metabolism/pathology, Molecular Weight, Neoplastic/chemically induced/metabolism/pathology, p38 Mitogen-Activated Protein Kinases/metabolism, PAHs, Rats, Receptors, Signal Transduction/drug effects, Time Factors, Transcription, Tumor Necrosis Factor-alpha/*toxicity},

pubstate = {published},

tppubtype = {article}

}

@article{andrysik_aryl_2013,

title = {Aryl hydrocarbon receptor-mediated disruption of contact inhibition is associated with connexin43 downregulation and inhibition of gap junctional intercellular communication.},

author = {Zdeněk Andrysík and Jiřina Procházková and Markéta Kabátková and Lenka Umannová and Pavlína Simečková and Jiří Kohoutek and Alois Kozubík and Miroslav Machala and Jan Vondráček},

doi = {10.1007/s00204-012-0963-7},

issn = {1432-0738 0340-5761},

year  = {2013},

date = {2013-03-01},

journal = {Archives of toxicology},

volume = {87},

number = {3},

pages = {491–503},

abstract = {The aryl hydrocarbon receptor (AhR) contributes to the control of cell-to-cell communication, cell adhesion, migration or proliferation. In the present study, we investigated the regulation of connexin43 (Cx43) and Cx43-mediated gap junctional intercellular communication (GJIC) during the AhR-dependent disruption of contact inhibition in non-tumorigenic liver epithelial cells. The contact inhibition of cell proliferation is a process restricting the cell division of confluent non-transformed cells, which is frequently abolished in cancer cells; however, the mechanisms contributing to its disruption are still only partially understood. Disruption of contact inhibition, which was induced by toxic AhR ligands 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or polycyclic aromatic hydrocarbons in epithelial WB-F344 cells, reduced Cx43 protein levels, possibly via enhanced proteasomal degradation, significantly decreased the amount of gap junction plaques and downregulated GJIC, in an AhR-dependent manner. Although both intracellular and membrane Cx43 pools were markedly reduced in cells released from contact inhibition by TCDD, siRNA-mediated Cx43 knock-down was not sufficient to stimulate proliferation in contact-inhibited cells. Our data suggest that downregulation of Cx43/GJIC in non-transformed epithelial cells is an inherent part of disruption of contact inhibition, which occurs at the post-transcriptional level. This process runs in parallel with alterations of other forms of cell-to-cell communication, thus suggesting that toxic AhR agonists may simultaneously abrogate contact inhibition and reduce GJIC, two essential mechanisms linked to deregulation of cell-to-cell communication during tumor promotion and progression.},

note = {Place: Germany},

keywords = {Animals, Aryl Hydrocarbon/*agonists/genetics/metabolism, Benz(a)Anthracenes/toxicity, Carcinogens/*toxicity, Cell Communication/*drug effects, Cell Line, Cell Proliferation, Cell Transformation, Connexin 43/genetics/*metabolism, Contact Inhibition/*drug effects, Dose-Response Relationship, Down-Regulation, Drug, Epithelial Cells/*drug effects/metabolism/pathology, Fluorenes/toxicity, Gap Junctions/*drug effects/metabolism/pathology, Gene Knockdown Techniques, Indoles/pharmacology, Ligands, Liver Neoplasms/chemically induced/metabolism/pathology, Liver/*drug effects/metabolism/pathology, Neoplastic/chemically induced/metabolism/pathology, Phloroglucinol/analogs & derivatives/pharmacology, Phosphorylation, Polychlorinated Dibenzodioxins/toxicity, Proteasome Endopeptidase Complex/metabolism, Rats, Receptors, RNA Interference, Signal Transduction/*drug effects, Time Factors, Transfection},

pubstate = {published},

tppubtype = {article}

}

@article{hruba_gene_2011,

title = {Gene expression changes in human prostate carcinoma cells exposed to genotoxic and nongenotoxic aryl hydrocarbon receptor ligands.},

author = {Eva Hrubá and Jan Vondráček and Helena Líbalová and Jan Topinka and Vítězslav Bryja and Karel Souček and Miroslav Machala},

doi = {10.1016/j.toxlet.2011.07.011},

issn = {1879-3169 0378-4274},

year  = {2011},

date = {2011-10-01},

journal = {Toxicology letters},

volume = {206},

number = {2},

pages = {178–188},

abstract = {Carcinogenic polycyclic aromatic hydrocarbons (PAHs) are known as efficient mutagens and ligands of the aryl hydrocarbon receptor (AhR), which has been suggested to play an important role in prostate carcinogenesis. In order to evaluate the complex relationship between the genotoxicity and the AhR-mediated activity of PAHs in prostate cells, we selected benzo[a]pyrene (BaP) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), as model genotoxic and nongenotoxic AhR ligands, respectively, to explore global changes in gene expression in LNCaP cells by microarray analysis. We identified 112 genes that were differentially expressed in cells treated for 24h with BaP, TCDD or both compounds. Our data indicated that the impacts of BaP and TCDD on transcriptome of LNCaP cells significantly overlap, since over 64% of significantly up-regulated genes and 47% of down-regulated genes were similarly affected by both AhR ligands. This suggested that the activation of AhR played a prominent role in the nongenotoxic effects of BaP in the prostate carcinoma cell model LNCaP. Both AhR ligands suppressed expression of genes associated with cell cycle progression, DNA replication, spindle assembly checkpoint or DNA repair, which probably occurred secondary to inhibition of cell cycle progression. In contrast, we identified Wnt5a, an important regulator of prostate cancer progression, to be induced as early as 6h after exposure to both AhR ligands. The AhR ligand-induced Wnt5a upregulation, together with other observed alterations of gene expression, may further contribute to enhanced cell plasticity of prostate carcinoma cells.},

note = {Place: Netherlands},

keywords = {Aryl Hydrocarbon/*agonists, Benzo(a)pyrene/*toxicity, Carcinogens, Carcinoma/metabolism, Cell Cycle/drug effects, Cell Line, DNA Repair/drug effects, DNA Replication/drug effects, Environmental/*toxicity, Gene Expression Profiling, Gene Expression Regulation, Humans, Ligands, Male, Mutagens/*toxicity, Neoplastic/*drug effects, Oligonucleotide Array Sequence Analysis, Polychlorinated Dibenzodioxins/*toxicity, Prostatic Neoplasms/*metabolism, Proto-Oncogene Proteins/genetics/metabolism, Receptors, Spindle Apparatus/drug effects, Time Factors, Tumor, Wnt Proteins/genetics/metabolism, Wnt-5a Protein},

pubstate = {published},

tppubtype = {article}

}

@article{vanhara_growthdifferentiation_2009,

title = {Growth/differentiation factor-15 inhibits differentiation into osteoclasts–a novel factor involved in control of osteoclast differentiation.},

author = {Petr Vanhara and Eva Lincová and Alois Kozubík and Pierre Jurdic and Karel Soucek and Jan Smarda},

doi = {10.1016/j.diff.2009.07.008},

issn = {1432-0436 0301-4681},

year  = {2009},

date = {2009-11-01},

journal = {Differentiation; research in biological diversity},

volume = {78},

number = {4},

pages = {213–222},

abstract = {Survival and capability of cancer cells to form metastases fundamentally depend on interactions with their microenvironment. Secondary tumors originating from prostate carcinomas affect remodeling of bone tissue and can induce both osteolytic and osteocondensing lesions. However, particular molecular mechanisms responsible for selective homing and activity of cancer cells in bone microenvironment have not been clarified yet. Growth/differentiation factor-15 (GDF-15), a distant member of the TGF-beta protein family, has recently been associated with many human cancers, including prostate. We show that both pure GDF-15 and the GDF-15-containing growth medium of 1,25(OH)(2)-vitamin D(3)-treated prostate adenocarcinoma LNCaP cells suppress formation of mature osteoclasts differentiated from RAW264.7 macrophages and bone-marrow precursors by M-CSF/RANKL in a dose-dependent manner. GDF-15 inhibits expression of c-Fos and activity of NFkappaB by delayed degradation of IkappaB. Moreover, GDF-15 inhibits expression of carbonic anhydrase II and cathepsin K, key osteoclast enzymes, and induces changes in SMAD and p38 signaling. The lack of functional osteoclasts can contribute to accumulation of bone matrix by reduction of bone resorption. These results unveil new role of GDF-15 in modulation of osteoclast differentiation and possibly in therapy of bone metastases.},

note = {Place: England},

keywords = {Acid Phosphatase/metabolism, Animals, Calcitriol/pharmacology, Carbonic Anhydrase II/antagonists & inhibitors, Cathepsin K/antagonists & inhibitors/genetics, Cell Differentiation/*drug effects, Cell Line, Conditioned/pharmacology, Culture Media, Dose-Response Relationship, Drug, Femur/cytology, Growth Differentiation Factor 15/*pharmacology, Humans, Inbred Strains, Isoenzymes/metabolism, Macrophage Colony-Stimulating Factor/pharmacology, Macrophages/cytology, Male, Mice, NF-kappa B/antagonists & inhibitors, Osteoclasts/*drug effects/metabolism, Prostatic Neoplasms/metabolism, Proto-Oncogene Proteins c-fos/antagonists & inhibitors, RANK Ligand/pharmacology, Tartrate-Resistant Acid Phosphatase, Time Factors, Tumor},

pubstate = {published},

tppubtype = {article}

}

@article{vistejnova_comparison_2009,

title = {The comparison of impedance-based method of cell proliferation monitoring with commonly used metabolic-based techniques.},

author = {Lucie Vistejnova and Jana Dvorakova and Martina Hasova and Tomas Muthny and Vladimir Velebny and Karel Soucek and Lukas Kubala},

issn = {0172-780X},

year  = {2009},

date = {2009-01-01},

journal = {Neuro endocrinology letters},

volume = {30 Suppl 1},

pages = {121–127},

abstract = {OBJECTIVES: Determination of cell numbers is a crucial step in studies focused on cytokinetics and cell toxicity. The impedance-based analysis employing electronic sensor array system xCELLigence System allowing label-free dynamic monitoring of relative viable adherent cell amounts was compared with the most utilized methods for relative quantification of viable cell numbers based on a determination of cellular metabolism. DESIGN: Colorimetric assay based on reduction of tetrazolium salt (MTT) by mitochondrial enzymes and chemiluminiscent assay based on intracellular adenosine triphosphate (ATP) determination were compared with the impedance-based system. Cell morphology was compared by microscopic evaluation. Normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF), together with 3T3 mouse fibroblast and HaCaT keratinocyte cell lines were employed. RESULTS: The progress of cell growth curves obtained by different methods during 72 hours reflected cell type and cell seeding densities. The impedance-based method was found to be applicable for the determination of the cell proliferation of 3T3 fibroblasts, HaCaT and NHDF, since the comparison of this method with ATP and MTT determinations showed a comparable results. In contrast, the proliferation of NHEK measured by the impedance-based method did not correlate with other methodological approaches. This could be accounted to the specific morphological appearance of these cells. CONCLUSION: The study shows the impedance-based detection of viable adherent cells is a valuable approach for cytokinetics and pharmacological studies. However, the specific morphological characteristics of cell lines have to be considered employing this method for determination of cell proliferation without using other reference methods.},

note = {Place: Sweden},

keywords = {*Cell Proliferation, *Electric Impedance, 3T3 Cells, Adenosine Triphosphate/*metabolism, Animals, Cell Count/*methods, Cell Line, Cells, Colorimetry, Cultured, Dermis/cytology, Fibroblasts/cytology, Humans, Keratinocytes/cytology, Luminescent Measurements, Mice, Mitochondria/enzymology/metabolism, Oxidation-Reduction, Tetrazolium Salts/*metabolism, Time Factors},

pubstate = {published},

tppubtype = {article}

}

@article{stika_mk-886_2006,

title = {MK-886 enhances tumour necrosis factor-alpha-induced differentiation and apoptosis.},

author = {Jirí Stika and Jan Vondrácek and Jirina Hofmanová and Vladimír Simek and Alois Kozubík},

doi = {10.1016/j.canlet.2005.06.012},

issn = {0304-3835},

year  = {2006},

date = {2006-06-01},

journal = {Cancer letters},

volume = {237},

number = {2},

pages = {263–271},

abstract = {We investigated the role of the 5-lipoxygenase (5-LOX) pathway of arachidonic acid metabolism in tumour necrosis factor-alpha (TNF-alpha)-induced differentiation of human leukemic HL-60 cells using MK-886, an inhibitor of 5-LOX activating protein. MK-886 augmented cell cycle arrest and differentiation induced by TNF-alpha; however, both effects were probably 5-LOX-independent, because a general LOX inhibitor, NDGA, had no effect. Apoptosis was significantly elevated after combined TNF-alpha and MK-886 treatment, which could be partially associated with changes of Mcl-1 protein expression. NF-kappaB signalling or activation of JNKs were not modulated by MK-886. Thus, in addition to apoptosis, MK-886 can enhance TNF-alpha-induced differentiation.},

note = {Place: Ireland},

keywords = {*Apoptosis, Arachidonate 5-Lipoxygenase/metabolism, Cell Cycle, Cell Differentiation, Cell Line, Cell Survival, HL-60 Cells, Humans, Indoles/*pharmacology, Lipoxygenase Inhibitors/*pharmacology, Signal Transduction, Time Factors, Tumor, Tumor Necrosis Factor-alpha/*metabolism},

pubstate = {published},

tppubtype = {article}

}

@article{kubala_perioperative_2002,

title = {Perioperative and postoperative course of cytokines and the metabolic activity of neutrophils in human cardiac operations and heart transplantation.},

author = {Lukás Kubala and Milan Cíz and Jan Vondrácek and Jan Cerný and Petr Nemec and Pavel Studeník and Hana Cizová and Antonín Lojek},

doi = {10.1067/mtc.2002.125814},

issn = {0022-5223},

year  = {2002},

date = {2002-12-01},

journal = {The Journal of thoracic and cardiovascular surgery},

volume = {124},

number = {6},

pages = {1122–1129},

abstract = {OBJECTIVES: The purpose of this study was to compare systemic inflammatory responses after heart transplantation and nontransplant cardiac operations, both involving cardiopulmonary bypass with a focus on the role of polymorphonuclear leukocytes. METHODS: Lipid peroxidation, blood phagocyte radical production, and interleukin 6, 8, and 10 plasma concentrations during surgical intervention and on the first and seventh postoperative days were evaluated in patients undergoing heart transplantation (n = 24) and in patients not undergoing transplantation (n = 30). RESULTS: Levels of interleukin 6, 8, and 10 increased in both groups of patients during early reperfusion. They normalized within the first postoperative day in the transplant group, whereas the nontransplant group's interleukin 6 and 8 levels remained increased on the seventh day after the operation. Interleukin 10 plasma levels were higher in the heart transplant group during reperfusion. Lipid peroxidation was increased after the operation in both groups of patients. Phagocyte activity was enhanced at reperfusion and at all other sampling times only in the nontransplant group. On the other hand, phagocyte activity oscillated around the preoperative level during heart transplantation, or it was even decreased. CONCLUSION: Both cardiac operations involving heart transplantation and those without transplantation are associated with increased oxidative stress and an enhanced production of proinflammatory and anti-inflammatory cytokines. Differences in interleukin 10 production and phagocyte activity could be caused mainly by the immunosuppressive therapy in heart transplant operations.},

note = {Place: United States},

keywords = {*Cardiac Surgical Procedures, *Heart Transplantation, Cardiopulmonary Bypass, Cytokines/*metabolism, Female, Humans, Interleukin-10/metabolism, Interleukin-6/metabolism, Interleukin-8/metabolism, Male, Middle Aged, Neutrophils/*metabolism, oxidative stress, Phagocytosis, Time Factors},

pubstate = {published},

tppubtype = {article}

}