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Dentistry and OMICS: Transcriptome Dynamics of an Oral Ecosystem as Measured by Changes in Oral Polymorphonuclear Neutrophils in Experimental Gingivitis

Rijkschroeff, P. (author), Schoenmaker, T. (author), Caspers, M. (author), Verschuren, L. (author), Keijser, B.J.F. (author), Nicu, E.A. (author), Loos, B.G. (author)

Oral health and dentistry are essential components of systems medicine, which has received lesser attention in comparison to other medical fields, such as cancer biology. In this context, oral polymorphonuclear neutrophils (oPMNs) play an important role in the maintenance of oral health. To the best of our knowledge, this is the first study to...

article 2020

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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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Novel role of the antimicrobial peptide LL-37 in the protection of neutrophil extracellular Traps against degradation by bacterial nucleases

Neumann, A. (author), Völlger, L. (author), Berends, E.T.M. (author), Molhoek, E.M. (author), Stapels, D.A.C. (author), Midon, M. (author), Friães, A. (author), Pingoud, A. (author), Rooijakkers, S.H.M. (author), Gallo, R.L. (author), Mörgelin, M. (author), Nizet, V. (author), Naim, H.Y. (author), von Köckritz-Blickwede, M. (author)

Neutrophil extracellular traps (NETs) have been described as a fundamental innate immune defence mechanism. They consist of a nuclear DNA backbone associated with different antimicrobial peptides (AMPs) which are able to engulf and kill pathogens. The AMP LL-37, a member of the cathelicidin family, is highly present in NETs. However, the...

article 2014

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Metabolically induced liver inflammation leads to NASH and differs from LPS-or IL-1β-induced chronic inflammation

Liang, W. (author), Lindeman, J.H. (author), Menke, A.L. (author), Koonen, D.P. (author), Morrison, M. (author), Havekes, L.M. (author), van den Hoek, A.M. (author), Kleemann, R. (author)

The nature of the chronic inflammatory component that drives the development of non-alcoholic steatohepatitis (NASH) is unclear and possible inflammatory triggers have not been investigated systematically. We examined the effect of non-metabolic triggers (lipopolysaccharide (LPS), interleukin-1β (IL-1β), administered by slow-release minipumps)...

article 2014

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The antimicrobial peptide LL-37 facilitates the formation of neutrophil extracellular traps

Neumann, A. (author), Berends, E.T.M. (author), Nerlich, A. (author), Molhoek, E.M. (author), Gallo, R.L. (author), Meerloo, T. (author), Nizet, V. (author), Naim, H.Y. (author), von Köckritz-Blickwede, M. (author)

NETs (neutrophil extracellular traps) have been described as a fundamental innate immune defence mechanism. Duringformation of NETs, the nuclear membrane is disrupted by an asyet unknown mechanism. In the present study we investigated the role of human cathelicidin LL-37 in nuclear membrane disruption and formation of NETs. Immunofluorescence...

article 2014

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The effect of PPE-induced emphysema and chronic LPS-induced pulmonary inflammation on atherosclerosis development in APOE*3-LEIDEN mice

Khedoe, P.P.S.J. (author), Wong, M.C. (author), Wagenaar, G.T.M. (author), Plomp, J.J. (author), van Eck, M. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Hiemstra, P.S. (author), Berbée, J.F.P. (author)

Background: Chronic obstructive pulmonary disease (COPD) is characterized by pulmonary inflammation, airways obstruction and emphysema, and is a risk factor for cardiovascular disease (CVD). However, the contribution of these individual COPD components to this increased risk is unknown. Therefore, the aim of this study was to determine the...

article 2013

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Oxazolone (OXA) is a respiratory allergen in Brown Norway rats

Kuper, C.F. (author), Radonjic, M. (author), van Triel, J. (author), Stierum, R. (author), de Groot, R.J. (author), Arts, J.H.E. (author)

Oxazolone (OXA) is a potent contact allergen in man, and it is used as a model Th1-allergen to test (Q)SAR's and screening assays for allergenic potential of chemicals. However, it elevates serum IgE levels and Thelper2 cytokines at relatively low doses in test animals, suggesting that it has also respiratory allergenic potential. The lack of...

article 2011

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The Netherlands twin register biobank: A resource for genetic epidemiological studies

Willemsen, G. (author), de Geus, E.J.C. (author), Bartels, M. (author), van Beijsterveldt, C.E.M.T. (author), Brooks, A.I. (author), Estourgie-van Burk, G.F. (author), Fugman, D.A. (author), Hoekstra, C. (author), Hottenga, J.-J. (author), Kluft, K. (author), Meijer, P. (author), Montgomery, G.W. (author), Rizzu, P. (author), Sondervan, D. (author), Smit, A.B. (author), Spijker, S. (author), Suchiman, H.E.D. (author), Tischfield, J.A. (author), Lehner, T. (author), Slagboom, P.E. (author), Boomsma, D.I. (author), TNO Kwaliteit van Leven (author)

In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am...

article 2010

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Increased matrix metalloproteinase-8 and -9 activity in patients with infarct rupture after myocardial infarction

van den Borne, S.W.M. (author), Cleutjens, J.P.M. (author), Hanemaaijer, R. (author), Creemers, E.E. (author), Smits, J.F.M. (author), Daemen, M.J.A.P. (author), Blankesteijn, W.M. (author), TNO Kwaliteit van Leven (author)

Background: Infarct rupture is a usually fatal complication of myocardial infarction (MI), for which no molecular mechanism has been described in humans. Experimental evidence in mouse models suggests that the degradation of the extracellular matrix by matrix metalloproteinases (MMPs) plays an important role in infarct rupture. The present study...

article 2009

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Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content

Abdul-Hussien, H. (author), Hanemaaijer, R. (author), Verheijen, J.H. (author), van Bockel, J.H. (author), Geelkerken, R.H. (author), Lindeman, J.H.N. (author), TNO Kwaliteit van Leven (author)

Background: Matrix metalloproteinase-9 (MMP-9) is thought to play a central role in abdominal aortic aneurysm (AAA) initiation. Doxycycline, a tetracycline analogue, has direct MMP-9-inhibiting properties in vitro, and it effectively suppresses AAA development in rodents. Observed inhibition of AAA progression, and contradictory findings in...

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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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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Preexposure to amorphous silica particles attenuates but also enhances allergic reactions in trimellitic anhydride-sensitized brown Norway rats

Arts, J.H.E. (author), Schijf, M.A. (author), Kuper, C.F. (author), TNO Kwaliteit van Leven (author)

Irritant-induced inflammation of the airways may aggravate respiratory allergy induced by chemical respiratory allergens. Therefore, the effect of airway irritation by synthetic amorphous silica (SAS) on respiratory allergy to trimellitic anhydride (TMA) was studied. Brown Norway (BN) rats were topically sensitized on day 0 and on day 7,...

article 2008

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Targeting the tetraspanin CD81 blocks monocyte transmigration and ameliorates EAE

Dijkstra, S. (author), Kooij, G. (author), Verbeek, R. (author), van der Pol, S.M.A. (author), Amor, S. (author), Geisert Jr., E.E. (author), Dijkstra, C.D. (author), van Noort, J.M. (author), Vries, H.E.D. (author), TNO Kwaliteit van Leven (author)

Leukocyte infiltration is a key step in the development of demyelinating lesions in multiple sclerosis (MS), and molecules mediating leukocyte-endothelial interactions represent prime candidates for the development of therapeutic strategies. Here we studied the effects of blocking the integrin-associated tetraspanin CD81 in in vitro and in vivo...

article 2008

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Development of atopic dermatitis in mice transgenic for human apolipoprotein C1

Nagelkerken, L. (author), Verzaal, P. (author), Lagerweij, T. (author), Persoon-Deen, C. (author), Berbee, J.F.P. (author), Prens, E.P. (author), Havekes, L.M. (author), Oranje, A.P. (author), TNO Kwaliteit van Leven (author)

Mice with transgenic expression of human apolipoprotein C1 (APOC1) in liver and skin have strongly increased serum levels of cholesterol, triglycerides, and free fatty acids, indicative of a disturbed lipid metabolism. Importantly, these mice display a disturbed skin barrier function, evident from increased transepidermal water loss, and...

article 2008

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Henoch-Schönlein purpura in children: An epidemiological study among Dutch paediatricians on incidence and diagnostic criteria

TNO Kwaliteit van Leven (author), Aalberse, J. (author), Dolman, K. (author), Ramnath, G. (author), Pereira, R.R. (author), Davin, J.C. (author)

Background: The aim of the present study on the occurrence of Henoch-Schönlein Purpura (HSP) in Dutch children is to give some insight into the epidemiology of HSP in the Netherlands, to record the diagnostic criteria used by Dutch paediatricians and to evaluate the accuracy of the latter using the presence of IgA in the skin when biopsies are...

article 2007

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Inhibition of complement component C3 reduces vein graft atherosclerosis in apolipoprotein E3-Leiden transgenic mice

Schepers, A. (author), de Vries, M.R. (author), van Leuven, C.J. (author), Grimbergen, J.M. (author), Holers, V.M. (author), Daha, M.R. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

BACKGROUND - Venous bypass grafts may fail because of development of intimal hyperplasia and accelerated atherosclerosis. Inflammation plays a major role in these processes. Complement is an important part of the immune system and participates in the regulation of inflammation. The exact role of complement in the process of accelerated...

article 2006

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Gingival tissue and crevicular fluid co-operation in adult periodontitis

Beklen, A. (author), Tüter, G. (author), Sorsa, T. (author), Hanemaaijer, R. (author), Virtanen, I. (author), Tervahartiala, T. (author), Konttinen, Y.T. (author)

Activated matrix metalloproteinase-3 (MMP-3) can contribute to periodontal ligament destruction in adult periodontitis. Since MMP-3 has been reported to activate proMMP-8 and -9, it was speculated that gingival tissue fibroblast-derived MMP-3 might, in periodontitis, be responsible for activation of gingival crevicular fluid (GCF) neutrophil...

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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Matrix metalloproteinase-2 is a consistent prognostic factor in gastric cancer

TNO Kwaliteit van Leven (author), Kubben, F.J.G.M. (author), Sier, C.F.M. (author), van Duijn, W. (author), Griffioen, G. (author), Hanemaaijer, R. (author), van de Velde, C.J.H. (author), van Krieken, J.H.J.M. (author), Lamers, C.B.H.W. (author), Verspaget, H.W. (author)

In a pioneer study, we showed 10 years ago that enhanced tissue levels of the matrix metalloproteinases (MMPs) MMP-2 and MMP-9 in gastric cancers, as determined by zymography, were related with worse overall survival of the patients. To corroborate these observations, we now assessed MMP-2 and MMP-9 with new techniques in an expanded group of...

article 2006