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Metabolic flux analysis of a phenol producing mutant of Pseudomonas putida S12: Verification and complementation of hypotheses derived from transcriptomics

Wierckx, N. (author), Ruijssenaars, H.J. (author), de Winde, J.H. (author), Schmid, A. (author), Blank, L.M. (author), TNO Kwaliteit van Leven (author)

The physiological effects of genetic and transcriptional changes observed in a phenol producing mutant of the solvent-tolerant Pseudomonas putida S12 were assessed with metabolic flux analysis. The upregulation of a malate/lactate dehydrogenase encoding gene could be connected to a flux increase from malate to oxaloacetate. A mutation in the...

article 2009

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Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids

Kersten, S. (author), Lichtenstein, L. (author), Steenbergen, E. (author), Mudde, K. (author), Hendriks, H.F.J. (author), Hesselink, M.K. (author), Schrauwen, P. (author), Müller, M. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE-: Plasma lipoprotein levels are determined by the balance between lipoprotein production and clearance. Recently, angiopoietin-like protein 4 (ANGPTL4) was uncovered as a novel endocrine factor that potently raises plasma triglyceride levels by inhibiting triglyceride clearance. However, very little is known about ANGPTL4 in human....

article 2009

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Transcriptome analysis of a phenol-producing Pseudomonas putida S12 construct: Genetic and physiological basis for improved production

Wierckx, N.J.P. (author), Ballerstedt, H. (author), de Bont, J.A.M. (author), de Winde, J.H. (author), Ruijssenaars, H.J. (author), Wery, J. (author), TNO Kwaliteit van Leven (author)

The unknown genetic basis for improved phenol production by a recombinant Pseudomonas putida S12 derivative bearing the tpl (tyrosine-phenol lyase) gene was investigated via comparative transcriptomics, nucleotide sequence analysis, and targeted gene disruption. We show upregulation of tyrosine biosynthetic genes and possibly decreased...

article 2008

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Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice

van der Hoorn, J.W.A. (author), de Haan, W. (author), Berbée, J.P.P. (author), Havekes, L.M. (author), Jukema, J.W. (author), Rensen, P.C. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)

Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human...

article 2008

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Toll-like receptor 3 on adult human astrocytes triggers production of neuroprotective mediators

Bsibsi, M. (author), Persoon-Deen, C. (author), Verwer, R.W.H. (author), Meeuwsen, S. (author), Ravid, R. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

Toll-like receptors (TLRs) are innate immunity receptors that are expressed on a wide range of cell types, including CNS glial cells. In general, TLR engagement by specific sets of microbial ligands triggers production of pro-inflammatory factors and enhances antigen-presenting cell functions. The functional roles of TLR in the CNS, however, are...

article 2006

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Beta-adrenergic receptor agonists induce the release of granulocyte chemotactic protein-2, oncostatin M, and vascular endothelial growth factor from macrophages

Verhoeckx, K.C.M. (author), Doornbos, R.P. (author), Witkamp, R.F. (author), van der Greef, J. (author), Rodenburg, R.J.T. (author), TNO Kwaliteit van Leven (author)

Vascular endothelial growth factor (VEGF), oncostatin M (OSM), and granulocyte chemotactic protein-2 (GCP-2/CXCL6) are up-regulated in U937 macrophages and peripheral blood macrophages exposed to LPS, beta-adrenergic receptor (β2-AR) agonists (e.g. zilpaterol, and clenbuterol) and some other agents that induce intracellular cAMP (prostaglandin...

article 2006

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In search of secreted protein biomarkers for the anti-inflammatory effect of β2-adrenergic receptor agonists: Application of DIGE technology in combination with multivariate and univariate data analysis tools

Verhoeckx, K.C.M. (author), Gaspari, M. (author), Bijlsma, S. (author), van der Greef, J. (author), Witkamp, R.F. (author), Doornbos, R.P. (author), Rodenburg, R.J.T. (author), TNO Kwaliteit van Leven (author)

Two-dimensional difference gel electrophoresis (DIGE) in combination with univariate (Student's t-test) and multivariate data analysis, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to study the anti-inflammatory effects of the β2-adrenergic receptor (β2-AR) agonist zilpaterol. U937...

article 2005

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Cultured human adult microglia from different donors display stable cytokine, chemokine and growth factor gene profiles but respond differently to a pro-inflammatory stimulus

Meeuwsen, S. (author), Bsibsi, M. (author), Persoon-Deen, C. (author), Ravid, R. (author), van Noort, J.M. (author), TNO Preventie en Gezondheid (author)

Objectives: Brain microglia are highly responsive cells in the central nervous system that exert key functions in host defense as well as in neuroprotection and regeneration. In this study the gene expression profiles for 268 cytokines, chemokines, growth factors and their receptors were examined in cultures of purified human adult microglia,...

article 2005

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Elevated formation of pyridinoline cross-links by profibrotic cytokines is associated with enhanced lysyl hydroxylase 2b levels

van der Slot, A.J. (author), van Dura, E.A. (author), de Wit, E.C. (author), de Groot, J. (author), Huizinga, T.W.J. (author), Bank, R.A. (author), Zuurmond, A.M. (author), TNO Preventie en Gezondheid (author)

The hallmark of fibrosis is the excessive accumulation of collagen. The deposited collagen contains increased pyridinoline cross-link levels due to an overhydroxylation of lysine residues within the collagen telopeptides. Lysyl hydroxylase 2b (LH2b) is the only lysyl hydroxylase consistently up-regulated in several forms of fibrosis, suggesting...

article 2005

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Tumor necrosis factor-α plays an important role in restenosis development

Monraats, P.S. (author), Pires, N.M.M. (author), Schepers, A. (author), Agema, W.R.P. (author), Boesten, L.S.M. (author), de Vries, M.R. (author), Zwinderman, A.H. (author), de Maat, M.P.M. (author), Doevendans, P.A.F.M. (author), de Winter, R.J. (author), Tio, R.A. (author), Waltenberger, J. (author), 't Hart, L.M. (author), Frants, R.R. (author), Quax, P.H.A. (author), van Vlijmen, B.J.M. (author), Havekes, L.M. (author), van der Laarse, A. (author), van der Wall, E.E. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Genetic factors appear to be important in the restenotic process after percutaneous coronary intervention (PCI), as well as in inflammation, a pivotal factor in restenosis. TNFα, a key regulator of inflammatory responses, may exert critical influence on the development of restenosis after PCI. The GENetic DEterminants of Restenosis (GENDER)...

article 2005

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Osteopontin levels and increased disease activity in relapsing-remitting multiple sclerosis patients

Vogt, M.H.J. (author), Floris, S. (author), Killestein, J. (author), Knol, D.L. (author), Smits, M. (author), Barkhof, F. (author), Polman, C.H. (author), Nagelkerken, L. (author)

Osteopontin (OPN) has been identified as the most prominent cytokine-encoding gene expressed within multiple sclerosis (MS) lesions. Recently, we demonstrated that OPN plasma levels were elevated in active relapsing-remitting (RR) MS patients. In this longitudinal study, a trend was observed for OPN serum levels in relation to clinical...

article 2004

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Evidence for anti-inflammatory activity of statins and PPARα activators in human C-reactive protein transgenic mice in vivo and in cultured human hepatocytes in vitro

Kleemann, R. (author), Verschuren, L. (author), de Rooij, B.J. (author), Lindeman, J. (author), de Maat, M.M. (author), Szalai, A.J. (author), Princen, H.M.G. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

Inflammatory processes, aside from cholesterol, play a central role in atherogenesis. Human C-reactive protein (huCRP) signals systemic inflammation and independently predicts future cardiovascular risk. Cholesterol-lowering statins reduce atherosclerosis and plasma huCRP levels. Evidence is sought for a direct anti-inflammatory statin effect in...

article 2004

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The direct peroxisome proliferator-activated receptor target fasting-induced adipose factor (FIAF/PGAR/ANGPTL4) is present in blood plasma as a truncated protein that is increased by fenofibrate treatment

TNO Preventie en Gezondheid (author), Mandard, S. (author), Zandbergen, F. (author), Nguan, S.T. (author), Escher, P. (author), Patsouris, D. (author), Koenig, W. (author), Kleemann, R. (author), Bakker, A. (author), Veenman, F. (author), Wahli, W. (author), Müller, M. (author), Kersten, S. (author)

The fasting-induced adipose factor (FIAF, ANGPTL4, PGAR, HFARP) was previously identified as a novel adipocytokine that was up-regulated by fasting, by peroxisome proliferator-activated receptor agonists, and by hypoxia. To further characterize FIAF, we studied regulation of FIAF mRNA and protein in liver and adipose cell lines as well as in...

article 2004

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The development of clinical activity in relapsing-remitting MS is associated with a decrease of FasL mRNA and an increase of Fas mRNA in peripheral blood

Lopatinskaya, L. (author), Boxel van-Dezaire, A.H.H. (author), Barkhof, F. (author), Polman, C.H. (author), Lucas, C.J. (author), Nagelkerken, L. (author)

In this longitudinal study, we examined the expression of Fas, FasL, CCR3, CCR5 and CXCR3 mRNA in peripheral blood mononuclear cells (PBMCs) of secondary progressive (SP) and relapsing-remitting (RR) multiple sclerosis (MS) patients. In RR patients, FasL, CCR3 and CCR5 mRNA levels were increased prior to the exacerbations, but these decreased...

article 2003

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Expression of macrophage migration inhibitory factor in different stages of human atherosclerosis

Burger-Kentischer, A. (author), Goebel, H. (author), Seiler, R. (author), Fraedrich, G. (author), Schaefer, H.E. (author), Dimmeler, S. (author), Kleemann, R. (author), Bernhagen, J. (author), Ihling, C. (author), Gaubius Instituut TNO (author)

Background - Atherosclerosis is a chronic inflammatory response of the arterial wall to injury. Macrophage migration inhibitory factor (MIF), a cytokine with potent inflammatory functions, was thus considered to be important in atherosclerotic lesion evolution. Methods and Results - We studied the presence and distribution of MIF...

article 2002

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Differential expression of stress proteins in human adult astrocytes in response to cytokines

Bajramović, J.J. (author), Bsibsi, M. (author), Geutskens, S.B. (author), Hassankhan, R. (author), Verhulst, K.C. (author), Stege, G.J.J. (author), de Groot, C.J.A. (author), van Noort, J.M. (author), TNO Preventie en Gezondheid (author)

Various lines of evidence suggest a close relationship between heat shock proteins (hsp) and several autoimmune diseases such as arthritis, diabetes and multiple sclerosis. While enhanced expression of hsp in autoimmune diseases is often regarded as a non-specific bystander effect of the inflammatory process, surprisingly little is known on hsp...

article 2000

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Selection of Arabidopsis mutants overexpressing genes driven by the promoter of an auxin-inducible glutathione S-transferase gene

van der Kop, D.A.M. (author), Schuyer, M. (author), Pinas, J.E. (author), van der Zaal, B.J. (author), Hooykaas, P.J.J. (author), Centraal Instituut voor Voedingsonderzoek TNO (author)

Transgenic arabidopsis plants were isolated that contained a T-DNA construct in which the promoter of an auxin-inducible glutathione S-transferase (GST) gene from tobacco was fused to the kanamycin resistance (nptII) as well as to the β-glucuronidase (gusA) reporter gene. Subsequently, seeds were treated with EMS to obtain mutants in which both...

article 1999

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Differential regulation of interleukin-10 (IL-10) and IL-12 by glucocorticoids in vitro

Visser, J. (author), van Boxel-Dezaire, A. (author), Methorst, D. (author), Brunt, T. (author), de Kloet, E.R. (author), Nagelkerken, L. (author), TNO Preventie en Gezondheid (author)

Antigen-presenting cells are thought to modulate the development of Th1 and Th2 cells by the secretion of interleukin-10 (IL-10) and IL-12. Because glucocorticoids (GC) favor the development of Th2 responses, we determined whether dexamethasone (DEX) and hydrocortisone (HC) have differential effects on lipopolysaccharide-induced IL-10 and IL-12...

article 1998

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Tumor necrosis factor-alpha regulates expression of vascular endothelial growth factor receptor-2 and of its co-receptor neuropilin-1 in human vascular endothelial cells

TNO Preventie en Gezondheid (author), Giraudo, E. (author), Primo, L. (author), Audero, E. (author), Gerber, H.P. (author), Koolwijk, P. (author), Soker, S. (author), Klagsbrun, M. (author), Ferrara, N. (author), Bussolino, F. (author)

Tumor necrosis factor-alpha (TNF-alpha) modulates gene expression in endothelial cells and is angiogenic in vivo. TNF-alpha does not activate in vitro migration and proliferation of endothelium, and its angiogenic activity is elicited by synthesis of direct angiogenic inducers or of proteases. Here, we show that TNF-alpha up-regulates in a dose-...

article 1998

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Verocytotoxin inhibits mitogenesis and protein synthesis in purified human glomerular mesangial cells without affecting cell viability: Evidence for two distinct mechanisms

van Setten, P.A. (author), van Hinsbergh, V.W.M. (author), van den Heuvel, L.P.W.J. (author), van der Velden, T.J.A.N. (author), van de Kar, N.C.A.J. (author), Krebbers, R.J.M. (author), Karmali, M.A. (author), Monnens, L.A.H. (author), Gaubius Instituut TNO (author)

Acute renal failure is one of the hallmarks of the hemolytic uremic syndrome (HUS). Infection with a verocytotoxin (VT)- or Shiga-like toxin (SLT)-producing Escherichia coli has been strongly implicated in the etiology of the epidemic form of HUS. The functional receptor for these closely related toxins appears to be a glycosphingolipid,...

article 1997