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Seeking Windows of Opportunity to Shape Lifelong Immune Health A Network-Based Strategy to Predict and Prioritize Markers of Early Life Immune Modulation

van Bilsen, J.H.M. (author), Dulos, R. (author), van Stee, M.F. (author), Meima, M.Y. (author), Rouhani Rankouhi, T. (author), Neergaard Jacobsen, L. (author), Staudt Kvistgaard, A. (author), Garthoff, J.A. (author), Knippels, L.M.J. (author), Knipping, K. (author), Houben, G.F. (author), Verschuren, L. (author), Meijerink, M. (author), Krishnan, S. (author)

A healthy immune status is strongly conditioned during early life stages. Insights into the molecular drivers of early life immune development and function are prerequisite to identify strategies to enhance immune health. Even though several starting points for targeted immune modulation have been identified and are being developed into...

article 2020

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NF-B-mediated metabolic remodelling in the inflamed heart in acute viral myocarditis

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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Plasticity of lifelong calorie-restricted C57BL/6J mice in adapting to a medium-fat diet intervention at old age

Rusli, F. (author), Boekschoten, M.V. (author), Borelli, V. (author), Sun, C. (author), Lute, C. (author), Menke, A.L. (author), van den Heuvel, J. (author), Salvioli, S. (author), Franceschi, C. (author), Müller, M. (author), Steegenga, W.T. (author)

Calorie restriction (CR) is a dietary regimen that supports healthy aging. In this study, we investigated the systemic and liver-specific responses caused by a diet switch to a medium-fat (MF) diet in 24-month-old lifelong, CR-exposed mice. This study aimed to increase the knowledge base on dietary alterations of gerontological relevance. Nine...

article 2018

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Intraileal casein infusion increases plasma concentrations of amino acids in humans A randomized cross over trial

Ripken, D. (author), van Avesaat, M. (author), Troost, F.J. (author), Masclee, A.A. (author), Witkamp, R.F. (author), Hendriks, H.F. (author)

Background. Activation of the ileal brake by casein induces satiety signals and reduces energy intake. However, adverse effects of intraileal casein administration have not been studied before. These adverse effects may include impaired amino acid digestion, absorption and immune activation. Objective. To investigate the effects of intraileal...

article 2017

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Effects of anthocyanin and flavanol compunds on lipid metabolism and adipose tissue associated systemic inflammation in diet-induced obesity

van der Heijden, R.A. (author), Morrison, M.C. (author), Sheedfar, F. (author), Mulder, P. (author), Schreurs, M. (author), Hommelberg, P.P.H. (author), Hofker, M.H. (author), Schalkwijk, C. (author), Kleemann, R. (author), Tietge, U.J.F. (author), Koonen, D.P.Y. (author), Heeringa, P. (author)

Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential....

article 2016

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Hematopoietic α7 nicotinic acetylcholine receptor deficiency increases inflammation and platelet activation status, but does not aggravate atherosclerosis

Kooijman, S. (author), Meurs, I. (author), van der Stoep, M. (author), Habets, K.L. (author), Lammers, B. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), van Eck, M. (author), Romijn, J.A. (author), Korporaal, S.J.A. (author), Rensen, P.C.N. (author)

Summary: Background: The autonomic nervous system attenuates inflammation through activation of the α7 nicotinic acetylcholine receptor (α7nAChR), a pathway termed the cholinergic anti-inflammatory reflex. Interestingly, α7nAChR is expressed on immune cells and platelets, both of which play a crucial role in the development of atherosclerosis....

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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Low-grade inflammation, diet composition and health: Current research evidence and its translation

Minihane, A.M. (author), Vinoy, S. (author), Russell, W.R. (author), Baka, A. (author), Roche, H.M. (author), Tuohy, K.M. (author), Teeling, J.L. (author), Blaak, E.E. (author), Fenech, M. (author), Vauzour, D. (author), McArdle, H.J. (author), Kremer, B.H.A. (author), Sterkman, L. (author), Vafeiadou, K. (author), Benedetti, M.M. (author), Williams, C.M. (author), Calder, P.C. (author)

The importance of chronic low-grade inflammation in the pathology of numerous age-related chronic conditions is now clear. An unresolved inflammatory response is likely to be involved from the early stages of disease development. The present position paper is the most recent in a series produced by the International Life Sciences Institute's...

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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Developmental immunotoxicity of ethanol in an extended one-generation reproductive toxicity study

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

The susceptibility of developing immune system to chemical disruption warrants the assessment of immune parameters in reproductive and developmental testing protocols. In this study, a wide range of immune endpoints was included in an extended one-generation reproduction toxicity study (EOGRTS) design to determine the relative sensitivity of...

article 2013

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Monounsaturated and Saturated, but Not n-6 Polyunsaturated Fatty Acids Decrease Cartilage Destruction under Inflammatory Conditions: A Preliminary Study

Bastiaansen-Jenniskens, Y.M. (author), Siawash, M. (author), van de Lest, C.H.A. (author), Verhaar, J.A.N. (author), Kloppenburg, M. (author), Zuurmond, A.M. (author), Stojanovic-Susulic, V. (author), van Osch, G.J.V.M. (author), Clockaerts, S. (author)

Purpose: Osteoarthritis (OA) is associated with obesity in which altered fatty acid levels have been observed. We investigated whether the most common fatty acids in synovial fluid influence cartilage deterioration in OA. Design: Cartilage was obtained from OA patients undergoing total knee arthroplasty. Chondrocytes or cartilage explants were...

article 2013

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Neonatal supplementation of processed supernatant from Lactobacillus rhamnosus GG improves allergic airway inflammation in mice later in life

Harb, H. (author), van Tol, E.A.F. (author), Heine, H. (author), Braaksma, M. (author), Gross, G. (author), Overkamp, K. (author), Hennen, M. (author), Alrifai, M. (author), Conrad, M.L. (author), Renz, H. (author), Garn, H. (author)

Background: Oral supplementation with probiotic bacteria can protect against the development of allergic and inflammatory diseases. Objective: The aim of this study was to investigate potential immunomodulatory and allergy-protective effects of processed Lactobacillus rhamnosus GG (LGG)-derived supernatants early in life in neonatal mice....

article 2013

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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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αB-crystallin is a target for adaptive immune responses and a trigger of innate responses in preactive multiple sclerosis lesions

van Noort, J.M. (author), Bsibsi, M. (author), Gerritsen, W.H. (author), van der Valk, P. (author), Bajramovic, J.J. (author), Steinman, L. (author), Amor, S. (author), TNO Kwaliteit van Leven (author)

We present the first comparative analysis of serum immunoglobulinG reactivity profiles against the full spectrum of human myelin-associated proteins in multiple sclerosis patients and healthy control subjects. In both groups, serum antibodies display a consistent and prominent reaction to αB-crystallin (CRYAB) versus other myelin proteins. As an...

article 2010

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Apolipoprotein CI enhances the biological response to LPS via the CD14/TLR4 pathway by LPS-binding elements in both its N- and C-terminal helix

TNO Kwaliteit van Leven (author), Berbé, J.F.P. (author), Coomans, C.P. (author), Westerterp, M. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author)

Timely sensing of lipopolysaccharide (LPS) is critical for the host to fight invading Gram-negative bacteria. We recently showed that apolipoprotein CI (apoCI) (apoCI1-57) avidly binds to LPS, involving an LPS-binding motif (apoCI48-54), and thereby enhances the LPS-induced inflammatory response. Our current aim was to further elucidate the...

article 2010

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ACE inhibition with perindopril and biomarkers of atherosclerosis and thrombosis: Results from the PERTINENT study

Ceconi, C. (author), Fox, K.M. (author), Remme, W.J. (author), Simoons, M.L. (author), Deckers, J.W. (author), Bertrand, M. (author), Parrinello, G. (author), Kluft, C. (author), Blann, A. (author), Cokkinos, D. (author), Ferrari, R. (author), TNO Kwaliteit van Leven (author)

The PERTINENT study measured biomarkers of atherosclerosis and thrombosis in a stable coronary artery disease population from EUROPA receiving ACE inhibition with perindopril 8 mg/day or placebo. Biomarkers of inflammation, C-reactive protein (CRP), fibrinogen, and tumor necrosis factor-alpha (TNF-α), and a biomarker of thrombosis, d-dimer, were...

article 2009

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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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Cytokines and atherosclerosis: A comprehensive review of studies in mice

Kleemann, R. (author), Zadelaar, A.S.M. (author), Kooistra, T. (author), Gaubius Instituut TNO (author)

In the past few years, inflammation has emerged as a major driving force of atherosclerotic lesion development. It is now well-established that from early lesion to vulnerable plaque formation, numerous cellular and molecular inflammatory components participate in the disease process. The most prominent cells that invade in evolving lesions are...

article 2008

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Immunologic activity of schistosomal and bacterial TLR2 ligands in Gabonese children

Retra, K. (author), van Riet, E. (author), Adegnika, A.A. (author), Everts, B. (author), van Geest, S. (author), Kremsner, P.G. (author), van Hellemond, J.J. (author), van der Kleij, D. (author), Tielens, A.G.M. (author), Yazdanbakhsh, M. (author), TNO Defensie en Veiligheid (author)

Schistosomes carry lipid moieties that interact with the immune system. To understand the consequence of interactions in terms of polarizing the cytokine profiles, the effect of two Toll-like receptor-2 (TLR2) activating schistosomal lipid fractions was studied on whole blood from Gabonese children living in a schistosomiasis endemic area. One...

article 2008

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Differential gene expression analysis of tubule forming and non-tubule forming endothelial cells: CDC42GAP as a counter-regulator in tubule formation

Engelse, M.A. (author), Laurens, N. (author), Verloop, R.E. (author), Koolwijk, P. (author), van Hinsbergh, V.W.M. (author), TNO Kwaliteit van Leven (author)

The formation of new tubular structures from a quiescent endothelial lining is one of the hallmarks of sprouting angiogenesis. This process can be mimicked in vitro by inducing capillary-like tubular structures in a three-dimensional (3D) fibrin matrix. We aimed to analyze the differential mRNA expression in two phenotypically distinct cell...

article 2008