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Remels, A.H.V. (author), Derks, W.J.A. (author), Cillero-Pastor, B. (author), Verhees, K.J.P. (author), Kelders, M.C. (author), Heggermont, W. (author), Carai, P. (author), Summer, G. (author), Ellis, S.R. (author), de Theije, C.C. (author), Heeren, R.M.A. (author), Heymans, S. (author), Papageorgiou, A.P. (author), van Bilsen, M. (author)Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac...article 2018
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Bosgra, S. (author), van de Steeg, E. (author), Vlaming, M.L. (author), Verhoeckx, K.C. (author), Huisman, M.T. (author), Verwei, M. (author), Wortelboer, H.M. (author)In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter abundance between cell-lines and tissue is by...article 2014
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Eefting, D. (author), Seghers, L. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), de Boer, H.C. (author), Lardenoye, J.W.H.P. (author), Jukema, J.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)Aims Matrix metalloproteinases (MMP) and plasminogen activator (PA)/plasmin-mediated proteolysis, especially at the cell surface, play important roles in matrix degeneration and smooth muscle cell migration, which largely contributes to vein graft failure. In this study, a novel hybrid protein was designed to inhibit both protease systems...article 2010
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Boele, L.C.L. (author), Bajramovic, J.J. (author), de Vries, A.M.M.B.C. (author), Voskamp-Visser, I.A.I. (author), Kaman, W.E. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)Activation of pattern recognition receptors such as Toll-like receptors (TLRs) by pathogens leads to activation and maturation of dendritic cells (DC), which orchestrate the development of the adaptive immune response. To create an overview of the effects of a broad range of pathogenic bacteria, their capacity to activate TLRs and to affect DC...article 2009
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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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Koudstaal, W. (author), Hartgroves, L. (author), Havenga, M. (author), Legastelois, I. (author), Ophorst, C. (author), Siewerts, M. (author), Zuijdgeest, D. (author), Vogels, R. (author), Custers, J. (author), de Boer-Luijtze, E. (author), de Leeuw, O. (author), Cornelissen, L. (author), Goudsmit, J. (author), Barclay, W. (author), TNO Kwaliteit van Leven (author)Reverse genetics, the generation of influenza viruses from cDNA, presents a rapid method for creating vaccine strains. The technique necessitates the use of cultured cells. Due to technical and regulatory requirements, the choice of cell lines for production of human influenza vaccines is limited. PER.C6® cells, among the most extensively...article 2009
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Ladics, G.S. (author), van Bilsen, J.H.M. (author), Brouwer, H.M.H. (author), Vogel, L. (author), Vieths, S. (author), Knippels, L.M.J. (author), TNO Kwaliteit van Leven (author), KvL (author)Specific IgE sera screening studies are employed to investigate protein cross-reactivity. Such nonfunctional immunochemical methods cannot measure the biological activity of proteins. Therefore, an assay using RBL cells transfected with human FcεRI was developed. Our objective was to evaluate the degranulation of three cell-lines expressing...article 2008
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Glycolipid-dependent sorting of melanosomal from lysosomal membrane proteins by lumenal determinantsGroux-Degroote, S. (author), van Dijk, S.M. (author), Wolthoorn, J. (author), Neumann, S. (author), Theos, A.C. (author), de Mazière, A.M. (author), Klumperman, J. (author), van Meer, G. (author), Sprong, H. (author), TNO Kwaliteit van Leven (author)Melanosomes are lysosome-related organelles that coexist with lysosomes in mammalian pigment cells. Melanosomal and lysosomal membrane proteins share similar sorting signals in their cytoplasmic tail, raising the question how they are segregated. We show that in control melanocytes, the melanosomal enzymes tyrosinase-related protein 1 (Tyrp1)...article 2008
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Fabriek, B.O. (author), Møller, H.J. (author), Vloet, R.P.M. (author), van Winsen, L.M. (author), Hanemaaijer, R. (author), Teunissen, C.E. (author), Uitdehaag, B.M.J. (author), van den Berg, T.K. (author), Dijkstra, C.D. (author), TNO Kwaliteit van Leven (author)The scavenger receptor CD163 is selectively expressed on tissue macrophages and human monocytes. CD163 has been implicated to play a role in the clearance of hemoglobin and in the regulation of cytokine production by macrophages. Membrane CD163 can be cleaved by matrix metalloproteinases (MMP) resulting in soluble CD163 (sCD163). In the present...article 2007
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Bsibsi, M. (author), Bajramovic, J.J. (author), van Duijvenvoorden, E. (author), Persoon, C. (author), Ravid, R. (author), van Noort, J.M. (author), Vogt, M.H.J. (author), TNO Kwaliteit van Leven (author)Human astrocytes express a limited repertoire of Toll-like receptor (TLR) family members including TLR1-4, which are expressed on the cell surface. Also, TLR3 but not TLR4 activation on astrocytes induces expression of several factors involved in neuroprotection and down-regulation of inflammation rather than in the onset of traditional pro...article 2007
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van Bezooijen, R.L. (author), Svensson, J.P. (author), Eefting, D. (author), Visser, A. (author), van der Horst, G. (author), Karperien, M. (author), Quax, P.H.A. (author), Vrieling, H. (author), Papapoulos, S.E. (author), ten Dijke, P. (author), Löwik, W.G.M.C. (author), TNO Kwaliteit van Leven (author)Sclerostin is an osteocyte-derived negative regulator of bone formation. It inhibits BMP-stimulated bone formation both in vitro and in vivo but has no direct effect on BMP signaling. Instead, sclerostin inhibits Wnt signaling that is required for BMP-stimulated osteoblastic differentiation. Introduction: Sclerostin is a member of the Dan family...article 2007
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Boerboom, A.M.J.F. (author), Vermeulen, M. (author), van der Woude, H. (author), Bremer, B.I. (author), Lee-Hilz, Y.Y. (author), Kampman, E. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Aarts, J.M.M.J.G. (author), TNO Kwaliteit van Leven (author)The electrophile-responsive element (EpRE) is a transcriptional enhancer involved in cancer-chemoprotective gene expression modulation by certain food components. Two stably transfected luciferase reporter cell lines were developed, EpRE(hNQO1)-LUX and EpRE(mGST-Ya)-LUX, based on EpRE sequences from the human NAD(P)H:quinone oxidoreductase ...article 2006
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van Zanden, J.J. (author), de Mul, A. (author), Wortelboer, H.M. (author), Usta, M. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)In the present study, the effects of myricetin on either MRP1 or MRP2 mediated vincristine resistance in transfected MDCKII cells were examined. The results obtained show that myricetin can inhibit both MRP1 and MRP2 mediated vincristine efflux in a concentration dependent manner. The IC50 values for cellular vincristine transport inhibition by...article 2005
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Krom, Y.D. (author), Gras, J.C.E. (author), Frants, R.R. (author), Havekes, L.M. (author), van Berkel, T.J. (author), Biessen, E.A.L. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)Vascular smooth muscle (VSMC) and endothelial cells (EC) are particularly resistant to infection by type 5 adenovirus (Ad) vectors. To overcome this limitation and target Ad vectors to ubiquitously expressed α Vβ3/5 integrins, we have generated a linker protein consisting of the extracellular domain of the coxsackie adenovirus receptor (CAR)...article 2005
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Wortelboer, H.M. (author), Usta, M. (author), van Zanden, J.J. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)To study the possible interplay between glutathione metabolism of and MRP inhibition by thiol reactive compounds, the interactions of a series of α,β-unsaturated carbonyl compounds with multidrug resistance proteins 1 and 2 (MRP1/ABCC1 and MRP2/ABCC2) were studied. α,β-Unsaturated carbonyl compounds react with glutathione, and therefore either...article 2005
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van Zanden, J.J. (author), Wortelboer, H.M. (author), Bijlsma, S. (author), Punt, A. (author), Usta, M. (author), Bladeren, P.J.V. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Kwaliteit van Leven (author)In the present study, the effects of a large series of flavonoids on multidrug resistance proteins (MRPs) were studied in MRP1 and MRP2 transfected MDCKII cells. The results were used to define the structural requirements of flavonoids necessary for potent inhibition of MRP1- and MRP2-mediated calcein transport in a cellular model. Several of...article 2005
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TNO Kwaliteit van Leven (author), Gerritsen, G. (author), Rensen, P.C.N. (author), Kypreos, K.E. (author), Zannis, V.I. (author), Havekes, L.M. (author), van Dijk, K.W. (author)Adenovirus-mediated overexpression of human apolipoprotein E (apoE) induces hyperlipidemia by stimulating the VLDL-triglyceride (TG) production rate and inhibiting the LPL-mediated VLDL-TG hydrolysis rate. Because apoC-III is a strong inhibitor of TG hydrolysis, we questioned whether Apoc3 deficiency might prevent the hyperlipidemia induced by...article 2005
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TNO Kwaliteit van Leven (author), van Kranenburg, R. (author), Golic, N. (author), Bongers, R. (author), Leer, R.J. (author), de Vos, W.M. (author), Siezen, R.J. (author), Kleerebezem, M. (author)Lactobacillus plantarum WCFS1 harbors three plasmids, pWCFS101, pWCFS102, and pWCFS103, with sizes of 1,917, 2,365, and 36,069 bp, respectively. The two smaller plasmids are of unknown function and contain replication genes that are likely to function via the rolling-circle replication mechanism. The host range of the p WCFS101 replicon includes...article 2005
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WU/TNO Center for Food Toxicology (author), van der Woude, H. (author), ter Veld, M.G.R. (author), Jacobs, N. (author), van der Saag, P.T. (author), Murk, A.J. (author), Rietjens, I.M.C.M. (author)Quercetin causes biphasic modulation of the proliferation of specific colon and mammary cancer cells. In this study, the possible involvement of the estrogen receptor (ER) in the stimulation of cell proliferation by quercetin was investigated. For this purpose, the effect of quercetin on cell prolifera-tion was tested in ER-positive MCF-7 and...article 2005
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van Zanden, J.J. (author), Geraets, L. (author), Wortelboer, H.M. (author), van Bladeren, P.J. (author), Rietjens, I.M.C.M. (author), Cnubben, N.H.P. (author), TNO Voeding (author)The objective of this study was to investigate the structural requirements necessary for inhibition of glutathione S-transferase P1-1 (GSTP1-1) and GS-X pump (MRP1 and MRP2) activity by structurally related flavonoids, in GSTP1-1 transfected MCF7 cells (pMTG5). The results reveal that GSTP1-1 activity in MCF7 pMTG5 cells can be inhibited by some...article 2004