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N-Acetylcysteine and Hydrogen Sulfide in Coronavirus Disease 2019

Bourgonje, A.R. (author), Offringa, A.K. (author), van Eijk, L.E. (author), Abdulle, A.E. (author), Hillebrands, J.L. (author), van der Voort, P.H.J. (author), van Goor, H. (author), van Hezik, E.J. (author)

Significance: Hydrogen sulfide (H2S) is one of the three main gasotransmitters that are endogenously produced in humans and are protective against oxidative stress. Recent findings from studies focusing on coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), shifted our attention to a...

article 2021

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Toll-like receptor 2 activation by β2→1-fructans protects barrier function of t84 human intestinal epithelial cells in a chain length-dependent manner

Vogt, L.M. (author), Meyer, D. (author), Pullens, G. (author), Faas, M.M. (author), Venema, K. (author), Ramasamy, U. (author), Schols, H.A. (author), de Vos, P. (author)

Dietary fiber intake is associated with lower incidence and mortality from disease, but the underlying mechanisms of these protective effects are unclear.We hypothesized that β2→1-fructan dietary fibers confer protection on intestinal epithelial cell barrier function via Toll-like receptor 2 (TLR2), and we studied whether β2→1-fructan chain...

article 2014

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RP105 deficiency aggravates cardiac dysfunction after myocardial infarction in mice

Louwe, M.C. (author), Karper, J.C. (author), de Vries, M.R. (author), Nossent, A.Y. (author), Bastiaansen, A.J.N.M. (author), van der Hoorn, J.W.A. (author), Willems Van Dijk, K. (author), Rensen, P.C.N. (author), Steendijk, P. (author), Smit, J.W.A. (author), Quax, P.H.A. (author)

Background Toll-like receptor-4 (TLR4), a receptor of the innate immune system, is suggested to have detrimental effects on cardiac function after myocardial infarction (MI). RP105 (CD180) is a TLR4 homolog lacking the intracellular signaling domain that competitively inhibits TLR4-signaling. Thus, we hypothesized that RP105 deficiency, by...

article 2014

document

P430RP105 deficiency aggravates cardiac dysfunction after myocardial infarction in mice

Louwe, M.C. (author), Karper, J.C. (author), de Vries, M.R. (author), Bastiaansen, A.J.N.M. (author), van der Hoorn, J.W.A. (author), Willems Van Dijk, K. (author), Rensen, P.C.N. (author), Steendijk, P. (author), Smit, J.W.A. (author), Quax, P.H.A. (author)

Purpose: Toll-like receptor-4 (TLR4), a receptor of the innate immune system, is suggested to have detrimental effects on cardiac function after myocardial infarction (MI). RP105 (CD180) is a TLR4 homolog lacking the intracellular signalling domain that competitively inhibits TLR4-signalling. Thus, we hypothesized that RP105 deficiency, by...

article 2014

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The probiotic mixture VSL#3 mediates both pro- and anti-inflammatory responses in bone marrow-derived dendritic cells from C57BL/6 and BALB/c mice

Mariman, R. (author), Kremer, S.H.A. (author), Koning, F. (author), Nagelkerken, L. (author)

Probiotic bacteria express a wide range of molecular structures that bind to receptors on innate immune cells and mediate health-promoting effects in the host. We have recently demonstrated in a colitis model that favourable effects of the probiotic mixture VSL#3 may in part be due to the suppression of intestinal chemokine expression. To obtain...

article 2014

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Probiotic bacteria and the immune system: mechanistic insights and therapeutic implications

Mariman, R. (author)

This thesis aimed to provide insight into the role of microbiota-host interactions in the regulation of mucosal and systemic immunity in the context of IBD. Regulation of microbiota composition (e.g. by probiotics and prebiotics) offers the possibility to modulate immune responses and contribute to the prevention and treatment of (autoimmune) -...

doctoral thesis 2013

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The microtubule regulator stathmin is an endogenous protein agonist for TLR3.

Bsibsi, M. (author), Bajramovic, J.J. (author), Vogt, M.H. (author), van Duijvenvoorden, E. (author), Baghat, A. (author), Persoon-Deen, C. (author), Tielen, F. (author), Verbeek, R. (author), Huitinga, I. (author), Ryffel, B. (author), Kros, A. (author), Gerritsen, W.H. (author), Amor, S. (author), van Noort, J.M. (author), TNO Kwaliteit van Leven (author)

TLR3 recognizes dsRNAs and is considered of key importance to antiviral host-defense responses. TLR3 also triggers neuroprotective responses in astrocytes and controls the growth of axons and neuronal progenitor cells, suggesting additional roles for TLR3-mediated signaling in the CNS. This prompted us to search for alternative, CNS-borne...

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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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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Structure-function relationship of the human antimicrobial peptide LL-37 and LL-37 fragments in the modulation of TLR responses

TNO Defensie en Veiligheid (author), Molhoek, E.M. (author), den Hertog, A.L. (author), de Vries, A.M.B.C. (author), Nazmi, K. (author), Veerman, E.C.I. (author), Hartgers, F.C. (author), Yazdanbakhsh, M. (author), Bikker, F.J. (author), van der Kleij, D. (author)

Cathelicidins are effector molecules of the innate host defense system that establish an antimicrobial barrier at epithelial interfaces. The human cathelicidin LL-37, in addition to its antimicrobial activity, also exhibits immunomodulatory effects, such as inhibition of pro-inflammatory responses to bacterial LPS in human monocytic cells. In...

article 2009

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Molecular characterization of trimellitic anhydride-induced respiratory allergy in Brown Norway rats

Kuper, C.F. (author), Heijne, W.H. (author), Dansen, M. (author), Verhoeckx, K.C. (author), Boorsma, A. (author), Radonjic, M. (author), Bruijntjes, J. (author), Stierum, R. (author), Muijser, H. (author), Arts, J.H. (author), TNO Kwaliteit van Leven (author)

To contribute to the hazard identification of low molecular weight (LMW) respiratory allergens, respiratory allergy induced by trimellitic anhydride (TMA) was characterized by whole genome analysis of lung tissue and blood proteomics in Brown Norway rats. Dermal sensitization (50% and 25% w/v) with TMA and an inhalation challenge of 15 mg/m(3)...

article 2008

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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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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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Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction

TNO Kwaliteit van Leven (author), Timmers, L. (author), Sluijter, J.P.G. (author), van Keulen, J.K. (author), Hoefer, I.E. (author), Nederhoff, M.G.J. (author), Goumans, M.J. (author), Doevendans, P.A. (author), van Echteld, C.J.A. (author), Joles, J.A. (author), Quax, P.H. (author), Piek, J.J. (author), Pasterkamp, G. (author), de Kleijn, D.P.V. (author)

article 2008

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Differentiation of primary adult microglia alters their response to TLR8-mediated activation but not their capacity as APC

Zuiderwijk-Sick, E.A. (author), van der Putten, C. (author), Bsibsi, M. (author), Deuzing, I.P. (author), de Boer, W. (author), Persoon-Deen, C. (author), Kondova, I. (author), Boven, L.A. (author), van Noort, J.M. (author), 't Hart, B.A. (author), Amor, S. (author), Bajramovic, J.J. (author), TNO Defensie en Veiligheid TNO Kwaliteit van Leven (author)

Activated microglia are found in a variety of neuroinflammatory disorders where they have attributed roles as effector as well as antigen-presenting cells (APC). Critical determinants for the multifaceted role of microglia are the differentiation potential of microglia and their mode of activation. In this study, we have investigated the effects...

article 2007

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Toll-like receptors as targets for inflammation, development and repair in the central nervous system

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

Toll-like receptors (TLRs) that play key roles in inflammation are also widely expressed in the CNS. While they are well known to activate inflammatory responses to microbial products, TLRs fulfill additional roles in the absence of infection. Emerging evidence suggests that several TLRs play a role in CNS development during fetal life and in...

article 2007

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Activation of the innate immune system in atherosclerotic disease

Oude Nijhuis, M.M. (author), van Keulen, J.K. (author), Pasterkamp, G. (author), Quax, P.H. (author), de Kleijn, D.P.V. (author), TNO Kwaliteit van Leven (author)

Innate immunity is the first line of defence against invading micro-organisms. The family of Toll-like receptors (TLRs) recognizes pathogen-associated molecular patterns (PAMPs) that are carried by the invading micro-organisms. Infectious pathogens have been implicated to play an important role in atherosclerosis. Nowadays, evidence is...

article 2007

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Identification of soluble CD14 as an endogenous agonist for toll-like receptor 2 on human astrocytes by genome-scale functional screening of glial cell derived proteins

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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Prolonged in vivo gene silencing by electroporation-mediated plasmid delivery of small interfering RNA

Eefting, D. (author), Grimbergen, J.M. (author), de Vries, M.R. (author), van Weel, V. (author), Kaijzel, E.L. (author), Que, I. (author), Moon, R.T. (author), Löwik, C.W. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

For the successful application of RNA interference in vivo, it is desired to achieve (local) delivery of small interfering RNAs (siRNAs) and long-term gene silencing. Nonviral electrodelivery is suitable to obtain local and prolonged expression of transgenes. By intramuscular electrodelivery of a plasmid in which two opposing human polymerase...

article 2007