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Detection of the mechanism of immunotoxicity of cyclosporine A in murine in vitro and in vivo models

Schmeits, P.C.J. (author), Schaap, M.M. (author), Luijten, M. (author), van Someren, E. (author), Boorsma, A. (author), van Loveren, H. (author), Peijnenburg, A.A.C.M. (author), Hendriksen, P.J.M. (author)

Transcriptomics in combination with in vitro cell systems is a powerful approach to unravel modes of action of toxicants. An important question is to which extent the modes of action as revealed by transcriptomics depend on cell type, species and study type (in vitro or in vivo). To acquire more insight into this, we assessed the transcriptomic...

article 2015

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Exposure to bisphenol A, but not phthalates, increases spontaneous diabetes type 1 development in NOD mice

Bodin, J. (author), Kocbach Bølling, A. (author), Wendt, A. (author), Eliasson, L. (author), Becher, R. (author), Kuper, F. (author), Løvik, M. (author), Nygaard, U.C. (author)

Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that...

article 2015

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Inflammation and nutritional science for programs/policies and interpretation of research evidence (INSPIRE)

Raiten, D.J. (author), Sakr Ashour, F.A. (author), Ross, A.C. (author), Meydani, S.N. (author), Dawson, H.D. (author), Stephensen, C.B. (author), Brabin, B.J. (author), Suchdev, P.S. (author), van Ommen, B. (author), Ahluwalia, N. (author), Ahmed, T. (author), Allen, L. (author), Beck, M. (author), Blanchard, H. (author), Brindle, E. (author), Brown, K. (author), Calder, P. (author), Checkley, W. (author), Claycombe, K. (author), Coles, C. (author), Esamai, F. (author), Friis, H. (author), Gardner, E. (author), Grinspoon, S. (author), Guerrant, R. (author), Hellerstein, M. (author), Hunt, J. (author), King, J. (author), Klasing, K. (author), Kramer, B. (author), Koski, K. (author), Northrop-Clewes, C. (author), Pfeiffer, C. (author), Prentice, A. (author), Ramirez-Zea, M. (author), van Rheenan, P. (author), Rink, L. (author), Srinivasa, S. (author), Benn, C.S. (author), Stephensen, C. (author), Suchdev, P. (author), Sullivan, K. (author), Thurnham, D. (author), Varadhan, R. (author), Van Der Ven, A. (author), Walston, J. (author), Xia, J. (author)

An increasing recognition has emerged of the complexities of the global health agenda-specifically, the collision of infections and noncommunicable diseases and the dual burden of over- and undernutrition. Of particular practical concern are both 1) the need for a better understanding of the bidirectional relations between nutritional status and...

article 2015

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Synovial inflammation, immune cells and their cytokines in osteoarthritis: A review

de Lange-Brokaar, B.J.E. (author), Ioan-Facsinay, A. (author), van Osch, G.J.V.M. (author), Zuurmond, A.-M. (author), Schoones, J. (author), Toes, R.E.M. (author), Huizinga, T.W.J. (author), Kloppenburg, M. (author)

Objective: Although osteoarthritis (OA) is considered a non-inflammatory condition, it is widely accepted that synovial inflammation is a feature of OA. However, the role of immune cells and their cytokines in OA is largely unknown. This narrative systematic review summarizes the knowledge of inflammatory properties, immune cells and their...

article 2012

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Gene expression profiling identifies mechanisms of protection to recurrent trinitrobenzene sulfonic acid colitis mediated by probiotics

Mariman, R. (author), Kremer, S.H.A. (author), van Erk, M. (author), Lagerweij, T. (author), Koning, F. (author), Nagelkerken, L. (author)

Background: Host-microbiota interactions in the intestinal mucosa play a major role in intestinal immune homeostasis and control the threshold of local inflammation. The aim of this study was to evaluate the efficacy of probiotics in the recurrent trinitrobenzene sulfonic acid (TNBS)-induced colitis model and gain more insight into protective...

article 2012

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Developmental immunotoxicity of methylmercury: The relative sensitivity of developmental and immune parameters

Tonk, E.C.M. (author), de Groot, D.M.G. (author), Penninks, A.H. (author), Waalkens - Berendsen, I.D.H. (author), Wolterbeek, A.P.M. (author), Slob, W. (author), Piersma, A.H. (author), van Loveren, H. (author), TNO Kwaliteit van Leven (author)

Current developmental and reproductive toxicity protocols include only a limited set of parameters for effects on the developing immune system. In this study, a wide range of immunological parameters were included in a pre- and postnatal developmental toxicity study. Dose-response data were compared to determine the relative sensitivity of...

article 2010

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Combined TLR2 and TLR4 ligation in the context of bacterial or helminth extracts in human monocyte derived dendritic cells: Molecular correlates for Th1/Th2 polarization

van Riet, E. (author), Everts, B. (author), Retra, K. (author), Phylipsen, M. (author), van Hellemond, J.J. (author), Tielens, A.G.M. (author), van der Kleij, D. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)

Background: Recognition of pathogens by dendritic cells (DCs) through interaction with pattern recognition receptors, including Toll like receptors (TLR), is crucial for the initiation of appropriate polarized T helper (Th) cell responses. Yet, the characteristics and differences in molecular profiles of DCs with different T cell polarizing...

article 2009

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Activation of toll-like receptors and dendritic cells by a broad range of bacterial molecules

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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Immune control of an SIV challenge by a T-cell-based vaccine in rhesus monkeys

Liu, J. (author), O'Brien, K.L. (author), Lynch, D.M. (author), Simmons, N.L. (author), La Porte, A. (author), Riggs, A.M. (author), Abbink, P. (author), Coffey, R.T. (author), Grandpre, L.E. (author), Seaman, M.S. (author), Landucci, G. (author), Forthal, D.N. (author), Montefiori, D.C. (author), Carville, A. (author), Mansfield, K.G. (author), Havenga, M.J. (author), Pau, M.G. (author), Goudsmit, J. (author), Barouch, D.H. (author), TNO Kwaliteit van Leven (author)

A recombinant adenovirus serotype 5 (rAd5) vector-based vaccine for HIV-1 has recently failed in a phase 2b efficacy study in humans. Consistent with these results, preclinical studies have demonstrated that rAd5 vectors expressing simian immunodeficiency virus (SIV) Gag failed to reduce peak or setpoint viral loads after SIV challenge of rhesus...

article 2009

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Clinical trial of doxycycline for matrix metalloproteinase-9 inhibition in patients with an abdominal aneurysm doxycycline selectively depletes aortic wall neutrophils and cytotoxic t cells

TNO Kwaliteit van Leven (author), Lindeman, J.H.N. (author), Abdul-Hussien, H. (author), van Bockel, J.H. (author), Wolterbeek, R. (author), Kleemann, R. (author)

Background-Doxycycline has been shown to effectively inhibit aneurysm formation in animal models of abdominal aortic aneurysm. Although this effect is ascribed to matrix metalloproteinase-9 inhibition, such an effect is unclear in human studies. We reevaluated the effect of doxycycline on aortic wall protease content in a inical trial and found...

article 2009

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Stress proteins in CNS inflammation

van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

Stress proteins or heat shock proteins (HSPs) are ubiquitous cellular components that have long been known to act as molecular chaperones. By assisting proper folding and transport of proteins, and by assisting in the degradation of aberrant proteins, they play key roles in cellular metabolism. The frequent accumulation of insoluble protein...

article 2008

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Enhanced expression and activation of pro-inflammatory transcription factors distinguish aneurysmal from atherosclerotic aorta: IL-6- and IL-8-dominated inflammatory responses prevail in the human aneurysm

Lindeman, J.H.N. (author), Abdul-Hussien, H. (author), Schaapherder, A.F.M. (author), van Bockel, J.H. (author), von der Thüsen, J.H. (author), Roelen, D.L. (author), Kleemann, R. (author)

Inflammation plays a key role in the pathogenesis of an AAA (abdominal aortic aneurysm); however, the nature of the inflammatory factors and cellular response(s) involved in AAA growth is controversial. In the present study, we set out to determine the aortic levels of inflammatory cytokines in relation to downstream inflammatory transcription...

article 2008

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Mannosylated self-peptide inhibits the development of experimental autoimmune encephalomyelitis via expansion of nonencephalitogenic T cells

Kel, J.M. (author), Slütter, B. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)

Tolerance to experimental autoimmune encephalomyelitis (EAE) in SJL mice can be induced by immunization with a mannosylated form of the proteolipid protein (M-PLP139-151), despite the presence of CFA. The state of tolerance is characterized by poor delayed-type hypersensitivity responses and the absence of clinical EAE symptoms. In vivo...

article 2008

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The evaluation of the immunomodulating properties of ERA-63 a pharmaceutical with estrogenic activity

Janssen, G.B. (author), Penninks, A.H. (author), Knippels, L.M.J. (author), van Zijverden, M. (author), Spanhaak, S. (author), TNO Kwaliteit van Leven (author)

This paper describes studies performed with ERA-63 a low molecular weight pharmaceutical with intended immunomodulatory effects. Since this compound was also known to have estrogenic activity a non-conventional approach was taken in order to differentiate between estrogenic and non-estrogenic-induced immunomodulatory effects. EE was included not...

article 2008

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Efficient degradation of gluten by a prolyl endoprotease in a gastrointestinal model: Implications for coeliac disease

Mitea, C. (author), Havenaar, R. (author), Wouter Drijfhout, J. (author), Edens, L. (author), Dekking, L. (author), Koning, F. (author), Dekking, E.H.A. (author), TNO Kwaliteit van Leven (author)

Background: Coeliac disease is caused by an immune response to gluten. As gluten proteins are proline rich they are resistant to enzymatic digestion in the gastrointestinal tract, a property that probably contributes to the immunogenic nature of gluten. Aims: This study determined the efficiency of gluten degradation by a post-proline cutting...

article 2008

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Identification and monitoring of effector and regulatory T cells during experimental arthritis based on differential expression of CD25 and CD134

Nolte-'t Hoen, E.N.M. (author), Boot, E.P.J. (author), Wagenaar-Hilbers, J.P.A. (author), van Bilsen, J.H.M. (author), Arkesteijn, G.J.A. (author), Storm, G. (author), Everse, L.A. (author), van Eden, W. (author), Wauben, M.H.M. (author), TNO Kwaliteit van Leven (author)

Major problems in the analysis of CD4+ effector cell and regulatory T cell (Treg) populations in an activated immune system are caused by the facts that both cell types can express CD25 and that the discriminatory marker forkhead box p3 can only be analyzed in nonviable (permeabilized) cells. Here, we show that CD134 (OX40) can be used as a...

article 2008

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Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation

Kel, J.M. (author), de Geus, E.D. (author), van Stipdonk, M.J. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)

In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA323-339). Immunization with M-OVA323-339 in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic...

article 2008

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Natural killer cells and CD4+ T-cells modulate collateral artery development

van Weel, V. (author), Toes, R.E.M. (author), Seghers, L. (author), Deckers, M.M.L. (author), de Vries, M.R. (author), Eilers, P.H. (author), Sipkens, J. (author), Schepers, A. (author), Eefting, D. (author), van Hinsbergh, V.W.M. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE - The immune system is thought to play a crucial role in regulating collateral circulation (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease. Here, we studied the role of lymphocytes in a murine model of hindlimb ischemia. METHODS AND RESULTS - Lymphocytes, detected with markers for NK1.1,...

article 2007

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Soluble mannosylated myelin peptide inhibits the encephalitogenicity of autoreactive T cells during experimental autoimmune encephalomyelitis

Kel, J. (author), Oldenampsen, J. (author), Luca, M. (author), Drijfhout, J.W. (author), Koning, F. (author), Nagelkerken, L. (author), TNO Kwaliteit van Leven (author)

We have previously shown that immunization with a mannosylated myelin peptide in complete adjuvant induces tolerance instead of disease in experimental autoimmune encephalomyelitis (EAE), a rodent model for multiple sclerosis. In this report we demonstrate that treatment with a soluble mannosylated epitope of proteolipid protein (M-PLP139-151)...

article 2007

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Interferon-β therapy reduces CD4+ and CD8+ T-cell reactivity in multiple sclerosis

Zafranskaya, M. (author), Oschmann, P. (author), Engel, R. (author), Weishaupt, A. (author), van Noort, J.M. (author), Jomaa, H. (author), Eberl, M. (author), TNO Kwaliteit van Leven (author)

Therapy with interferon-β (IFN-β) has well-established clinical effects in multiple sclerosis (MS), albeit the immunomodulatory mechanisms are not fully understood. We assessed the prevalence and functional capacity of CD4+ and CD8+ T cells in healthy donors, and in untreated and IFN-β-treated MS patients, in response to myelin oligodendrocyte...

article 2007