2021-heden
Technical Specialist NLP & Data science @ IBM
2017-2021
Senior AI consultant & Tech-ondernemer @ TXT-Insight B.V.
2015-2017
Manager Datalab @ Triskelion B.V.
2013-2015
Product Manager Toxicology @ Triskelion B.V.
2008-2013
Sr. Scientist/Project Leader @ ImmunAffect B.V.
2004-2008
Post Doc Onderzoeker @ Leids Universitair Medisch Centrum
2000-2004
Assistent in Opleiding @ Leids Universitair Medisch Centrum
1995-2000
Studie Fundamentele Biomedische Wetenschappen @ Utrecht Universiteit
Wetenschappelijke Publicaties
2015
Bakema, Jantine E; Tuk, Cornelis W; van Vliet, Sandra J; Bruijns, Sven C; Vos, Joost B; Letsiou, Sophia; Dijkstra, Christien D; van Kooyk, Yvette; Brenkman, Arjan B; van Egmond, Marjolein
Antibody-opsonized bacteria evoke an inflammatory dendritic cell phenotype and polyfunctional Th cells by cross-talk between TLRs and FcRs Journal Article
In: J Immunol, vol. 194, no. 4, pp. 1856–1866, 2015, ISSN: 1550-6606.
Abstract | Links | BibTeX | Tags:
@article{pmid25582855,
title = {Antibody-opsonized bacteria evoke an inflammatory dendritic cell phenotype and polyfunctional Th cells by cross-talk between TLRs and FcRs},
author = {Jantine E Bakema and Cornelis W Tuk and Sandra J van Vliet and Sven C Bruijns and Joost B Vos and Sophia Letsiou and Christien D Dijkstra and Yvette van Kooyk and Arjan B Brenkman and Marjolein van Egmond},
doi = {10.4049/jimmunol.1303126},
issn = {1550-6606},
year = {2015},
date = {2015-02-01},
journal = {J Immunol},
volume = {194},
number = {4},
pages = {1856--1866},
abstract = {During secondary immune responses, Ab-opsonized bacteria are efficiently taken up via FcRs by dendritic cells. We now demonstrate that this process induces cross-talk between FcRs and TLRs, which results in synergistic release of several inflammatory cytokines, as well as altered lipid metabolite profiles. This altered inflammatory profile redirects Th1 polarization toward Th17 cell responses. Interestingly, GM-CSF-producing Th cells were synergistically evoked as well, which suggests the onset of polyfunctional Th17 cells. Synergistic cytokine release was dependent on activation via MyD88 and ITAM signaling pathways through TLRs and FcRs, respectively. Cytokine regulation occurred via transcription-dependent mechanisms for TNF-α and IL-23 and posttranscriptional mechanisms for caspase-1-dependent release of IL-1β. Furthermore, cross-talk between TLRs and FcRs was not restricted to dendritic cells. In conclusion, our results support that bacteria alone initiate fundamentally different immune responses compared with Ab-opsonized bacteria through the combined action of two classes of receptors and, ultimately, may refine new therapies for inflammatory diseases.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
During secondary immune responses, Ab-opsonized bacteria are efficiently taken up via FcRs by dendritic cells. We now demonstrate that this process induces cross-talk between FcRs and TLRs, which results in synergistic release of several inflammatory cytokines, as well as altered lipid metabolite profiles. This altered inflammatory profile redirects Th1 polarization toward Th17 cell responses. Interestingly, GM-CSF-producing Th cells were synergistically evoked as well, which suggests the onset of polyfunctional Th17 cells. Synergistic cytokine release was dependent on activation via MyD88 and ITAM signaling pathways through TLRs and FcRs, respectively. Cytokine regulation occurred via transcription-dependent mechanisms for TNF-α and IL-23 and posttranscriptional mechanisms for caspase-1-dependent release of IL-1β. Furthermore, cross-talk between TLRs and FcRs was not restricted to dendritic cells. In conclusion, our results support that bacteria alone initiate fundamentally different immune responses compared with Ab-opsonized bacteria through the combined action of two classes of receptors and, ultimately, may refine new therapies for inflammatory diseases.
2014
Vogelpoel, Lisa T C; Hansen, Ivo S; Rispens, Theo; Muller, Femke J M; van Capel, Toni M M; Turina, Maureen C; Vos, Joost B; Baeten, Dominique L P; Kapsenberg, Martien L; de Jong, Esther C; den Dunnen, Jeroen
Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages Journal Article
In: Nat Commun, vol. 5, pp. 5444, 2014, ISSN: 2041-1723.
Abstract | Links | BibTeX | Tags:
@article{pmid25392121,
title = {Fc gamma receptor-TLR cross-talk elicits pro-inflammatory cytokine production by human M2 macrophages},
author = {Lisa T C Vogelpoel and Ivo S Hansen and Theo Rispens and Femke J M Muller and Toni M M van Capel and Maureen C Turina and Joost B Vos and Dominique L P Baeten and Martien L Kapsenberg and Esther C de Jong and Jeroen den Dunnen},
doi = {10.1038/ncomms6444},
issn = {2041-1723},
year = {2014},
date = {2014-11-01},
journal = {Nat Commun},
volume = {5},
pages = {5444},
abstract = {M2 macrophages suppress inflammation in numerous disorders, including tumour formation, infection and obesity. However, the exact role of M2 macrophages in the context of several other diseases is still largely undefined. We here show that human M2 macrophages promote inflammation instead of suppressing inflammation on simultaneous exposure to complexed IgG (c-IgG) and TLR ligands, as occurs in the context of diseases such as rheumatoid arthritis (RA). c-IgG-TLR ligand co-stimulation of M2 macrophages selectively amplifies production of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and promotes Th17 responses, which all play a critical role in RA pathology. Induction of pro-inflammatory cytokines on c-IgG co-stimulation mainly depends on Fc gamma receptor IIa (FcγRIIa), which selectively amplifies cytokine gene transcription and induces caspase-1 activation. These data indicate that FcγR-TLR cross-talk may be targeted for treatment to attenuate inflammation in RA, by restoring the anti-inflammatory function of M2 macrophages.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
M2 macrophages suppress inflammation in numerous disorders, including tumour formation, infection and obesity. However, the exact role of M2 macrophages in the context of several other diseases is still largely undefined. We here show that human M2 macrophages promote inflammation instead of suppressing inflammation on simultaneous exposure to complexed IgG (c-IgG) and TLR ligands, as occurs in the context of diseases such as rheumatoid arthritis (RA). c-IgG-TLR ligand co-stimulation of M2 macrophages selectively amplifies production of pro-inflammatory cytokines TNF-α, IL-1β and IL-6 and promotes Th17 responses, which all play a critical role in RA pathology. Induction of pro-inflammatory cytokines on c-IgG co-stimulation mainly depends on Fc gamma receptor IIa (FcγRIIa), which selectively amplifies cytokine gene transcription and induces caspase-1 activation. These data indicate that FcγR-TLR cross-talk may be targeted for treatment to attenuate inflammation in RA, by restoring the anti-inflammatory function of M2 macrophages.
2013
Reijerkerk, Arie; Lopez-Ramirez, M Alejandro; van Het Hof, Bert; Drexhage, Joost A R; Kamphuis, Wouter W; Kooij, Gijs; Vos, Joost B; van der Pouw Kraan, Tineke C T M; van Zonneveld, Anton J; Horrevoets, Anton J; Prat, Alexandre; Romero, Ignacio A; de Vries, Helga E
MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: implications for multiple sclerosis Journal Article
In: J Neurosci, vol. 33, no. 16, pp. 6857–6863, 2013, ISSN: 1529-2401.
Abstract | Links | BibTeX | Tags:
@article{pmid23595744,
title = {MicroRNAs regulate human brain endothelial cell-barrier function in inflammation: implications for multiple sclerosis},
author = {Arie Reijerkerk and M Alejandro Lopez-Ramirez and Bert van Het Hof and Joost A R Drexhage and Wouter W Kamphuis and Gijs Kooij and Joost B Vos and Tineke C T M van der Pouw Kraan and Anton J van Zonneveld and Anton J Horrevoets and Alexandre Prat and Ignacio A Romero and Helga E de Vries},
doi = {10.1523/JNEUROSCI.3965-12.2013},
issn = {1529-2401},
year = {2013},
date = {2013-04-01},
journal = {J Neurosci},
volume = {33},
number = {16},
pages = {6857--6863},
abstract = {Blood-brain barrier (BBB) dysfunction is a major hallmark of many neurological diseases, including multiple sclerosis (MS). Using a genomics approach, we defined a microRNA signature that is diminished at the BBB of MS patients. In particular, miR-125a-5p is a key regulator of brain endothelial tightness and immune cell efflux. Our findings suggest that repair of a disturbed BBB through microRNAs may represent a novel avenue for effective treatment of MS.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Blood-brain barrier (BBB) dysfunction is a major hallmark of many neurological diseases, including multiple sclerosis (MS). Using a genomics approach, we defined a microRNA signature that is diminished at the BBB of MS patients. In particular, miR-125a-5p is a key regulator of brain endothelial tightness and immune cell efflux. Our findings suggest that repair of a disturbed BBB through microRNAs may represent a novel avenue for effective treatment of MS.
2009
van Solingen, Coen; Seghers, Leonard; Bijkerk, Roel; Duijs, Jacques M G J; Roeten, Marko K; van Oeveren-Rietdijk, Annemarie M; Baelde, Hans J; Monge, Matthieu; Vos, Joost B; de Boer, Hetty C; Quax, Paul H A; Rabelink, Ton J; van Zonneveld, Anton Jan
Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis Journal Article
In: J Cell Mol Med, vol. 13, no. 8A, pp. 1577–1585, 2009, ISSN: 1582-4934.
Abstract | Links | BibTeX | Tags:
@article{pmid19120690,
title = {Antagomir-mediated silencing of endothelial cell specific microRNA-126 impairs ischemia-induced angiogenesis},
author = {Coen van Solingen and Leonard Seghers and Roel Bijkerk and Jacques M G J Duijs and Marko K Roeten and Annemarie M van Oeveren-Rietdijk and Hans J Baelde and Matthieu Monge and Joost B Vos and Hetty C de Boer and Paul H A Quax and Ton J Rabelink and Anton Jan van Zonneveld},
doi = {10.1111/j.1582-4934.2008.00613.x},
issn = {1582-4934},
year = {2009},
date = {2009-08-01},
journal = {J Cell Mol Med},
volume = {13},
number = {8A},
pages = {1577--1585},
abstract = {MicroRNAs are negative regulators of gene expression that play a key role in cell-type specific differentiation and modulation of cell function and have been proposed to be involved in neovascularization. Previously, using an extensive cloning and sequencing approach, we identified miR-126 to be specifically and highly expressed in human endothelial cells (EC). Here, we demonstrate EC-specific expression of miR-126 in capillaries and the larger vessels in vivo. We therefore explored the potential role of miR-126 in arteriogenesis and angiogenesis. Using miR-reporter constructs, we show that miR-126 is functionally active in EC in vitro and that it could be specifically repressed using antagomirs specifically targeting miR-126. To study the consequences of miR-126 silencing on vascular regeneration, mice were injected with a single dose of antagomir-126 or a control 'scramblemir' and exposed to ischemia of the left hindlimb by ligation of the femoral artery. Although miR-126 was effectively silenced in mice treated with a single, high dose (HD) of antagomir-126, laser Doppler perfusion imaging did not show effects on blood flow recovery. In contrast, quantification of the capillary density in the gastrocnemius muscle revealed that mice treated with a HD of antagomir-126 had a markedly reduced angiogenic response. Aortic explant cultures of the mice confirmed the role of miR-126 in angiogenesis. Our data demonstrate a facilitary function for miR-126 in ischemia-induced angiogenesis and show the efficacy and specificity of antagomir-induced silencing of EC-specific microRNAs in vivo.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
MicroRNAs are negative regulators of gene expression that play a key role in cell-type specific differentiation and modulation of cell function and have been proposed to be involved in neovascularization. Previously, using an extensive cloning and sequencing approach, we identified miR-126 to be specifically and highly expressed in human endothelial cells (EC). Here, we demonstrate EC-specific expression of miR-126 in capillaries and the larger vessels in vivo. We therefore explored the potential role of miR-126 in arteriogenesis and angiogenesis. Using miR-reporter constructs, we show that miR-126 is functionally active in EC in vitro and that it could be specifically repressed using antagomirs specifically targeting miR-126. To study the consequences of miR-126 silencing on vascular regeneration, mice were injected with a single dose of antagomir-126 or a control 'scramblemir' and exposed to ischemia of the left hindlimb by ligation of the femoral artery. Although miR-126 was effectively silenced in mice treated with a single, high dose (HD) of antagomir-126, laser Doppler perfusion imaging did not show effects on blood flow recovery. In contrast, quantification of the capillary density in the gastrocnemius muscle revealed that mice treated with a HD of antagomir-126 had a markedly reduced angiogenic response. Aortic explant cultures of the mice confirmed the role of miR-126 in angiogenesis. Our data demonstrate a facilitary function for miR-126 in ischemia-induced angiogenesis and show the efficacy and specificity of antagomir-induced silencing of EC-specific microRNAs in vivo.
2007
Vos, Joost B; Datson, Nicole A; Rabe, Klaus F; Hiemstra, Pieter S
Exploring host-pathogen interactions at the epithelial surface: application of transcriptomics in lung biology Journal Article
In: Am J Physiol Lung Cell Mol Physiol, vol. 292, no. 2, pp. L367–L377, 2007, ISSN: 1040-0605.
Abstract | Links | BibTeX | Tags:
@article{pmid17041013,
title = {Exploring host-pathogen interactions at the epithelial surface: application of transcriptomics in lung biology},
author = {Joost B Vos and Nicole A Datson and Klaus F Rabe and Pieter S Hiemstra},
doi = {10.1152/ajplung.00242.2006},
issn = {1040-0605},
year = {2007},
date = {2007-02-01},
journal = {Am J Physiol Lung Cell Mol Physiol},
volume = {292},
number = {2},
pages = {L367--L377},
abstract = {The epithelial surface of the airways is the largest barrier-forming interface between the human body and the outside world. It is now well recognized that, at this strategic position, airway epithelial cells play an eminent role in host defense by recognizing and responding to microbial exposure. Conversely, inhaled microorganisms also respond to contact with epithelial cells. Our understanding of this cross talk is limited, requiring sophisticated experimental approaches to analyze these complex interactions. High-throughput technologies, such as DNA microarray analysis and serial analysis of gene expression (SAGE), have been developed to screen for gene expression levels at large scale within single experiments. Since their introduction, these hypothesis-generating technologies have been widely used in diverse areas such as oncology and brain research. Successful application of these genomics-based technologies has also revealed novel insights in host-pathogen interactions in both the host and pathogen. This review aims to provide an overview of the SAGE and microarray technology illustrated by their application in the analysis of host-pathogen interactions. In particular, the interactions between epithelial cells in the human lungs and clinically relevant microorganisms are the central focus of this review.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The epithelial surface of the airways is the largest barrier-forming interface between the human body and the outside world. It is now well recognized that, at this strategic position, airway epithelial cells play an eminent role in host defense by recognizing and responding to microbial exposure. Conversely, inhaled microorganisms also respond to contact with epithelial cells. Our understanding of this cross talk is limited, requiring sophisticated experimental approaches to analyze these complex interactions. High-throughput technologies, such as DNA microarray analysis and serial analysis of gene expression (SAGE), have been developed to screen for gene expression levels at large scale within single experiments. Since their introduction, these hypothesis-generating technologies have been widely used in diverse areas such as oncology and brain research. Successful application of these genomics-based technologies has also revealed novel insights in host-pathogen interactions in both the host and pathogen. This review aims to provide an overview of the SAGE and microarray technology illustrated by their application in the analysis of host-pathogen interactions. In particular, the interactions between epithelial cells in the human lungs and clinically relevant microorganisms are the central focus of this review.
Vos, J. B.
Molecular mechanisms of epithelial host defense in the airways PhD Thesis
2007, ISBN: 9789090213309.
Abstract | Links | BibTeX | Tags:
@phdthesis{nokey,
title = {Molecular mechanisms of epithelial host defense in the airways},
author = {J.B. Vos},
url = {https://scholarlypublications.universiteitleiden.nl/handle/1887/9749},
isbn = {9789090213309},
year = {2007},
date = {2007-01-11},
urldate = {2007-01-11},
abstract = {Airway epithelial cells are indispensable for the host defense system in the lungs. Various strategies by which epithelial cells protect the lungs against inhaled pathogens have been described. In spite of that, the molecular mechanisms by which epithelial cells initiate and control the host defense response have not been explored systematically. In this thesis, the molecular mechanisms underlying the initiation and regulation of the early epithelial host defense response in the airways were investigated. Using genomics technology, genes were identified to be associated with the early inflammatory response in airway epithelial cells. Many of the identified genes had previously not been associated with the host defense response against pathogens in the airways. The early epithelial host defense response is rapidly induced and transient of nature and can be divided into two phases. The initial phase is characterized by a stengthening of the physical barrier and is accompanied by the production of immune signaling molecules. In the proceeding phase, production of specialized antimicrobial agents occurs. Striking similarities were found in the molecular mechanisms of host defense in epithelial tissues of the airways and skin. Due to these similarities, genetic alterations in epithelial host defense mechanisms may explain the occurrence of inflammatory disorders at multiple sites of the body at the same time. These observations provide the basis for future investiations to further unravel the molecular mechanisms underlying epithelial host defense, both in the airways and other epithelial tissues.},
keywords = {},
pubstate = {published},
tppubtype = {phdthesis}
}
Airway epithelial cells are indispensable for the host defense system in the lungs. Various strategies by which epithelial cells protect the lungs against inhaled pathogens have been described. In spite of that, the molecular mechanisms by which epithelial cells initiate and control the host defense response have not been explored systematically. In this thesis, the molecular mechanisms underlying the initiation and regulation of the early epithelial host defense response in the airways were investigated. Using genomics technology, genes were identified to be associated with the early inflammatory response in airway epithelial cells. Many of the identified genes had previously not been associated with the host defense response against pathogens in the airways. The early epithelial host defense response is rapidly induced and transient of nature and can be divided into two phases. The initial phase is characterized by a stengthening of the physical barrier and is accompanied by the production of immune signaling molecules. In the proceeding phase, production of specialized antimicrobial agents occurs. Striking similarities were found in the molecular mechanisms of host defense in epithelial tissues of the airways and skin. Due to these similarities, genetic alterations in epithelial host defense mechanisms may explain the occurrence of inflammatory disorders at multiple sites of the body at the same time. These observations provide the basis for future investiations to further unravel the molecular mechanisms underlying epithelial host defense, both in the airways and other epithelial tissues.
2006
Thijssen, Dick H J; Vos, Joost B; Verseyden, Caroline; van Zonneveld, Anton Jan; Smits, Paul; Sweep, Fred C G J; Hopman, Maria T E; de Boer, Hetty C
Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training Journal Article
In: Aging Cell, vol. 5, no. 6, pp. 495–503, 2006, ISSN: 1474-9718.
Abstract | Links | BibTeX | Tags:
@article{pmid17081158,
title = {Haematopoietic stem cells and endothelial progenitor cells in healthy men: effect of aging and training},
author = {Dick H J Thijssen and Joost B Vos and Caroline Verseyden and Anton Jan van Zonneveld and Paul Smits and Fred C G J Sweep and Maria T E Hopman and Hetty C de Boer},
doi = {10.1111/j.1474-9726.2006.00242.x},
issn = {1474-9718},
year = {2006},
date = {2006-12-01},
journal = {Aging Cell},
volume = {5},
number = {6},
pages = {495--503},
abstract = {The number of hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is thought to be a marker for neovascularization and vascular repair. Because physical inactivity and aging are risk factors for cardiovascular diseases, these factors may influence the numbers of HSCs and EPCs. Therefore, we examined baseline and exercise-induced levels of HSCs and EPCs in sedentary and trained young and older men. To study the role of aging in eight sedentary young (19-28 years) and eight sedentary older men (67-76 years), baseline and acute exercise-induced numbers of HSCs (CD34+-cells) and EPCs (CD34+/VEGFR-2+-cells) were quantified by fluorescence-activated cell sorter (FACS) analysis. To examine the effect of chronic training, eight age-matched trained young men (18-28 years) were compared with sedentary young men, whereas older men performed an 8-week endurance training. Older men showed significantly lower baseline and exercise-induced levels of HSCs/EPCs than the young men (P < 0.05). In young and older men, acute exercise significantly increased HSCs (P < 0.01), but not EPCs. The absolute increase in numbers of HSCs was attenuated in older men (P = 0.03). Apart from the lower baseline numbers of EPCs after chronic training in older men, training status did not alter baseline or exercise-induced levels of HSCs/EPCs in young and older men. We concluded that advancing age results in lower circulating numbers of HSCs and EPCs and attenuates the acute exercise-induced increase in HSCs. Interestingly, in young as well as in older men chronic endurance training does not affect baseline and exercise-induced numbers of HSCs and EPCs.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The number of hematopoietic stem cells (HSC) and endothelial progenitor cells (EPC) is thought to be a marker for neovascularization and vascular repair. Because physical inactivity and aging are risk factors for cardiovascular diseases, these factors may influence the numbers of HSCs and EPCs. Therefore, we examined baseline and exercise-induced levels of HSCs and EPCs in sedentary and trained young and older men. To study the role of aging in eight sedentary young (19-28 years) and eight sedentary older men (67-76 years), baseline and acute exercise-induced numbers of HSCs (CD34+-cells) and EPCs (CD34+/VEGFR-2+-cells) were quantified by fluorescence-activated cell sorter (FACS) analysis. To examine the effect of chronic training, eight age-matched trained young men (18-28 years) were compared with sedentary young men, whereas older men performed an 8-week endurance training. Older men showed significantly lower baseline and exercise-induced levels of HSCs/EPCs than the young men (P < 0.05). In young and older men, acute exercise significantly increased HSCs (P < 0.01), but not EPCs. The absolute increase in numbers of HSCs was attenuated in older men (P = 0.03). Apart from the lower baseline numbers of EPCs after chronic training in older men, training status did not alter baseline or exercise-induced levels of HSCs/EPCs in young and older men. We concluded that advancing age results in lower circulating numbers of HSCs and EPCs and attenuates the acute exercise-induced increase in HSCs. Interestingly, in young as well as in older men chronic endurance training does not affect baseline and exercise-induced numbers of HSCs and EPCs.
Morsink, M C; Steenbergen, P J; Vos, J B; Karst, H; Joëls, M; Kloet, E R De; Datson, N A
Acute activation of hippocampal glucocorticoid receptors results in different waves of gene expression throughout time Journal Article
In: J Neuroendocrinol, vol. 18, no. 4, pp. 239–252, 2006, ISSN: 0953-8194.
Abstract | Links | BibTeX | Tags:
@article{pmid16503919,
title = {Acute activation of hippocampal glucocorticoid receptors results in different waves of gene expression throughout time},
author = {M C Morsink and P J Steenbergen and J B Vos and H Karst and M Joëls and E R De Kloet and N A Datson},
doi = {10.1111/j.1365-2826.2006.01413.x},
issn = {0953-8194},
year = {2006},
date = {2006-04-01},
journal = {J Neuroendocrinol},
volume = {18},
number = {4},
pages = {239--252},
abstract = {Several aspects of hippocampal cell function are influenced by adrenal-secreted glucocorticoids in a delayed, genomic fashion. Previously, we used Serial Analysis of Gene Expression to identify glucocorticoid receptor (GR)-induced transcriptional changes in the hippocampus at a fixed time point. However, because changes in mRNA levels are transient and most likely precede the effects on hippocampal cell function, the aim of the current study was to assess the transcriptional changes in a broader time window by generating a time curve of GR-mediated gene expression changes. Therefore, we used rat hippocampal slices obtained from adrenalectomised rats, substituted in vivo with low corticosterone pellets, predominantly occupying the hippocampal mineralocorticoid receptors. To activate GR, slices were treated in vitro with a high (100 nM) dose of corticosterone and gene expression was profiled 1, 3 and 5 h after GR-activation. Using Affymetrix GeneChips, a striking pattern with different waves of gene expression was observed, shifting from exclusively down-regulated genes 1 h after GR-activation to both up and down regulated genes 3 h after GR-activation. After 5 h, the response was almost back to baseline. Additionally, real-time quantitative polymerase chain reaction was used for validation of a selection of responsive genes including genes involved in neurotransmission and synaptic plasticity such as the corticotropin releasing hormone receptor 1, monoamine oxidase A, LIMK1 and calmodulin 2. This permitted confirmation of GR-responsiveness of 15 out of 18 selected genes. In conclusion, direct activation of GR in hippocampal slices results in transient changes in gene expression. The pattern in which gene expression was modulated suggests that the fast genomic effects of glucocorticoids may be realised via transrepression, preceding a later wave of transactivation. Furthermore, we identified a number of interesting candidate genes which may underlie the glucocorticoid-mediated effects on hippocampal cell function.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Several aspects of hippocampal cell function are influenced by adrenal-secreted glucocorticoids in a delayed, genomic fashion. Previously, we used Serial Analysis of Gene Expression to identify glucocorticoid receptor (GR)-induced transcriptional changes in the hippocampus at a fixed time point. However, because changes in mRNA levels are transient and most likely precede the effects on hippocampal cell function, the aim of the current study was to assess the transcriptional changes in a broader time window by generating a time curve of GR-mediated gene expression changes. Therefore, we used rat hippocampal slices obtained from adrenalectomised rats, substituted in vivo with low corticosterone pellets, predominantly occupying the hippocampal mineralocorticoid receptors. To activate GR, slices were treated in vitro with a high (100 nM) dose of corticosterone and gene expression was profiled 1, 3 and 5 h after GR-activation. Using Affymetrix GeneChips, a striking pattern with different waves of gene expression was observed, shifting from exclusively down-regulated genes 1 h after GR-activation to both up and down regulated genes 3 h after GR-activation. After 5 h, the response was almost back to baseline. Additionally, real-time quantitative polymerase chain reaction was used for validation of a selection of responsive genes including genes involved in neurotransmission and synaptic plasticity such as the corticotropin releasing hormone receptor 1, monoamine oxidase A, LIMK1 and calmodulin 2. This permitted confirmation of GR-responsiveness of 15 out of 18 selected genes. In conclusion, direct activation of GR in hippocampal slices results in transient changes in gene expression. The pattern in which gene expression was modulated suggests that the fast genomic effects of glucocorticoids may be realised via transrepression, preceding a later wave of transactivation. Furthermore, we identified a number of interesting candidate genes which may underlie the glucocorticoid-mediated effects on hippocampal cell function.
Vos, Joost B; Datson, Nicole A; van Kampen, Antoine H; Luyf, Angela C; Verhoosel, Renate M; Zeeuwen, Patrick L; Olthuis, Diana; Rabe, Klaus F; Schalkwijk, Joost; Hiemstra, Pieter S
A molecular signature of epithelial host defense: comparative gene expression analysis of cultured bronchial epithelial cells and keratinocytes Journal Article
In: BMC Genomics, vol. 7, pp. 9, 2006, ISSN: 1471-2164.
Abstract | Links | BibTeX | Tags:
@article{pmid16420688,
title = {A molecular signature of epithelial host defense: comparative gene expression analysis of cultured bronchial epithelial cells and keratinocytes},
author = {Joost B Vos and Nicole A Datson and Antoine H van Kampen and Angela C Luyf and Renate M Verhoosel and Patrick L Zeeuwen and Diana Olthuis and Klaus F Rabe and Joost Schalkwijk and Pieter S Hiemstra},
doi = {10.1186/1471-2164-7-9},
issn = {1471-2164},
year = {2006},
date = {2006-01-01},
journal = {BMC Genomics},
volume = {7},
pages = {9},
abstract = {BACKGROUND: Epithelia are barrier-forming tissues that protect the organism against external noxious stimuli. Despite the similarity in function of epithelia, only few common protective mechanisms that are employed by these tissues have been systematically studied. Comparative analysis of genome-wide expression profiles generated by means of Serial Analysis of Gene Expression (SAGE) is a powerful approach to yield further insight into epithelial host defense mechanisms. We performed an extensive comparative analysis of previously published SAGE data sets of two types of epithelial cells, namely bronchial epithelial cells and keratinocytes, in which the response to pro-inflammatory cytokines was assessed. These data sets were used to elucidate a common denominator in epithelial host defense.nnRESULTS: Bronchial epithelial cells and keratinocytes were found to have a high degree of overlap in gene expression. Using an in silico approach, an epithelial-specific molecular signature of gene expression was identified in bronchial epithelial cells and keratinocytes comprising of family members of keratins, small proline-rich proteins and proteinase inhibitors. Whereas some of the identified genes were known to be involved in inflammation, the majority of the signature represented genes that were previously not associated with host defense. Using polymerase chain reaction, presence of expression of selected tissue-specific genes was validated.nnCONCLUSION: Our comparative analysis of gene transcription reveals that bronchial epithelial cells and keratinocytes both express a subset of genes that is likely to be essential in epithelial barrier formation in these cell types. The expression of these genes is specific for bronchial epithelial cells and keratinocytes and is not seen in non-epithelial cells. We show that bronchial epithelial cells, similar to keratinocytes, express components that are able to form a cross-linked protein envelope that may contribute to an effective barrier against noxious stimuli and pathogens.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Epithelia are barrier-forming tissues that protect the organism against external noxious stimuli. Despite the similarity in function of epithelia, only few common protective mechanisms that are employed by these tissues have been systematically studied. Comparative analysis of genome-wide expression profiles generated by means of Serial Analysis of Gene Expression (SAGE) is a powerful approach to yield further insight into epithelial host defense mechanisms. We performed an extensive comparative analysis of previously published SAGE data sets of two types of epithelial cells, namely bronchial epithelial cells and keratinocytes, in which the response to pro-inflammatory cytokines was assessed. These data sets were used to elucidate a common denominator in epithelial host defense.nnRESULTS: Bronchial epithelial cells and keratinocytes were found to have a high degree of overlap in gene expression. Using an in silico approach, an epithelial-specific molecular signature of gene expression was identified in bronchial epithelial cells and keratinocytes comprising of family members of keratins, small proline-rich proteins and proteinase inhibitors. Whereas some of the identified genes were known to be involved in inflammation, the majority of the signature represented genes that were previously not associated with host defense. Using polymerase chain reaction, presence of expression of selected tissue-specific genes was validated.nnCONCLUSION: Our comparative analysis of gene transcription reveals that bronchial epithelial cells and keratinocytes both express a subset of genes that is likely to be essential in epithelial barrier formation in these cell types. The expression of these genes is specific for bronchial epithelial cells and keratinocytes and is not seen in non-epithelial cells. We show that bronchial epithelial cells, similar to keratinocytes, express components that are able to form a cross-linked protein envelope that may contribute to an effective barrier against noxious stimuli and pathogens.
2005
Tjabringa, G Sandra; Vos, Joost B; Olthuis, Diana; Ninaber, Dennis K; Rabe, Klaus F; Schalkwijk, Joost; Hiemstra, Pieter S; Zeeuwen, Patrick L J M
Host defense effector molecules in mucosal secretions Journal Article
In: FEMS Immunol Med Microbiol, vol. 45, no. 2, pp. 151–158, 2005, ISSN: 0928-8244.
Abstract | Links | BibTeX | Tags:
@article{pmid16051067,
title = {Host defense effector molecules in mucosal secretions},
author = {G Sandra Tjabringa and Joost B Vos and Diana Olthuis and Dennis K Ninaber and Klaus F Rabe and Joost Schalkwijk and Pieter S Hiemstra and Patrick L J M Zeeuwen},
doi = {10.1016/j.femsim.2005.03.004},
issn = {0928-8244},
year = {2005},
date = {2005-08-01},
journal = {FEMS Immunol Med Microbiol},
volume = {45},
number = {2},
pages = {151--158},
abstract = {Mucosal secretions contain a range of defense effector molecules including antimicrobial peptides and proteinase inhibitors. These molecules play a central role in host defense against infection, and in a variety of immune and inflammatory reactions. The aim of this study was to analyze the levels of neutrophil defensins, the cathelicidin hCAP-18/LL-37, and the proteinase inhibitors secretory leukocyte proteinase inhibitor, SKALP/elafin and cystatin M/E in various mucosal secretions and urine. We show here that especially seminal plasma is characterized by high concentrations of hCAP-18/LL-37, SLPI, SKALP/elafin and cystatin M/E. The results of this study demonstrate that each mucosal secretion is characterized by a unique profile of effector molecules, which may supply individual mucosal secretions with specific properties related to the control of local infection and inflammation.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Mucosal secretions contain a range of defense effector molecules including antimicrobial peptides and proteinase inhibitors. These molecules play a central role in host defense against infection, and in a variety of immune and inflammatory reactions. The aim of this study was to analyze the levels of neutrophil defensins, the cathelicidin hCAP-18/LL-37, and the proteinase inhibitors secretory leukocyte proteinase inhibitor, SKALP/elafin and cystatin M/E in various mucosal secretions and urine. We show here that especially seminal plasma is characterized by high concentrations of hCAP-18/LL-37, SLPI, SKALP/elafin and cystatin M/E. The results of this study demonstrate that each mucosal secretion is characterized by a unique profile of effector molecules, which may supply individual mucosal secretions with specific properties related to the control of local infection and inflammation.
Vos, Joost B; van Sterkenburg, Marianne A; Rabe, Klaus F; Schalkwijk, Joost; Hiemstra, Pieter S; Datson, Nicole A
Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense Journal Article
In: Physiol Genomics, vol. 21, no. 3, pp. 324–336, 2005, ISSN: 1531-2267.
Abstract | Links | BibTeX | Tags:
@article{pmid15701729,
title = {Transcriptional response of bronchial epithelial cells to Pseudomonas aeruginosa: identification of early mediators of host defense},
author = {Joost B Vos and Marianne A van Sterkenburg and Klaus F Rabe and Joost Schalkwijk and Pieter S Hiemstra and Nicole A Datson},
doi = {10.1152/physiolgenomics.00289.2004},
issn = {1531-2267},
year = {2005},
date = {2005-05-01},
journal = {Physiol Genomics},
volume = {21},
number = {3},
pages = {324--336},
abstract = {The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or heat-inactivated Pseudomonas aeruginosa. Because molecular mechanisms of epithelial innate host defense are not fully understood, the open-ended expression-profiling technique SAGE was applied to construct gene expression profiles covering 30,000 genes: 292 genes were found to be differentially expressed. Expression of seven genes was confirmed by real-time qPCR. Among differentially expressed genes, four classes or families were identified: keratins, proteinase inhibitors, S100 calcium-binding proteins, and IL-1 family members. Marked transcriptional changes were observed for keratins that form a key component of the cytoskeleton in epithelial cells. Expression of antimicrobial proteinase inhibitors SLPI and elafin was elevated after microbial or cytokine exposure. Interestingly, expression of numerous S100 family members was observed, and eight members, including S100A8 and S100A9, were among the most differentially expressed genes. Differential expression was also observed for the IL-1 family members IL-1beta, IL-1 receptor antagonist, and IL-1F9, a newly discovered IL-1 family member. Clustering of differentially expressed genes into biological processes revealed that the early inflammatory response in airway epithelial cells to IL-1beta-TNF-alpha and P. aeruginosa is characterized by expression of genes involved in epithelial barrier formation and host defense.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The airway epithelium responds to microbial exposure by altering expression of a variety of genes to increase innate host defense. We aimed to delineate the early transcriptional response in human primary bronchial epithelial cells exposed for 6 h to a mixture of IL-1beta and TNF-alpha or heat-inactivated Pseudomonas aeruginosa. Because molecular mechanisms of epithelial innate host defense are not fully understood, the open-ended expression-profiling technique SAGE was applied to construct gene expression profiles covering 30,000 genes: 292 genes were found to be differentially expressed. Expression of seven genes was confirmed by real-time qPCR. Among differentially expressed genes, four classes or families were identified: keratins, proteinase inhibitors, S100 calcium-binding proteins, and IL-1 family members. Marked transcriptional changes were observed for keratins that form a key component of the cytoskeleton in epithelial cells. Expression of antimicrobial proteinase inhibitors SLPI and elafin was elevated after microbial or cytokine exposure. Interestingly, expression of numerous S100 family members was observed, and eight members, including S100A8 and S100A9, were among the most differentially expressed genes. Differential expression was also observed for the IL-1 family members IL-1beta, IL-1 receptor antagonist, and IL-1F9, a newly discovered IL-1 family member. Clustering of differentially expressed genes into biological processes revealed that the early inflammatory response in airway epithelial cells to IL-1beta-TNF-alpha and P. aeruginosa is characterized by expression of genes involved in epithelial barrier formation and host defense.
2003
Duits, Louise A; Nibbering, Peter H; van Strijen, Elisabeth; Vos, Joost B; Mannesse-Lazeroms, Sylvia P G; van Sterkenburg, Marianne A J A; Hiemstra, Pieter S
Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells Journal Article
In: FEMS Immunol Med Microbiol, vol. 38, no. 1, pp. 59–64, 2003, ISSN: 0928-8244.
Abstract | Links | BibTeX | Tags:
@article{pmid12900056,
title = {Rhinovirus increases human beta-defensin-2 and -3 mRNA expression in cultured bronchial epithelial cells},
author = {Louise A Duits and Peter H Nibbering and Elisabeth van Strijen and Joost B Vos and Sylvia P G Mannesse-Lazeroms and Marianne A J A van Sterkenburg and Pieter S Hiemstra},
doi = {10.1016/S0928-8244(03)00106-8},
issn = {0928-8244},
year = {2003},
date = {2003-08-01},
journal = {FEMS Immunol Med Microbiol},
volume = {38},
number = {1},
pages = {59--64},
abstract = {Human beta-defensins (hBDs) are antimicrobial peptides that play important roles in host defense against infection, inflammation and immunity. Previous studies showed that micro-organisms and proinflammatory mediators regulate the expression of these peptides in airway epithelial cells. The aim of the present study was to investigate the modulation of expression of hBDs in cultured primary bronchial epithelial cells (PBEC) by rhinovirus-16 (RV16), a respiratory virus responsible for the common cold and associated with asthma exacerbations. RV16 was found to induce expression of hBD-2 and -3 mRNA in PBEC, but did not affect hBD-1 mRNA. Viral replication appeared essential for rhinovirus-induced beta-defensin mRNA expression, since UV-inactivated rhinovirus did not increase expression of hBD-2 and hBD-3 mRNA. Exposure to synthetic double-stranded RNA (dsRNA) molecule polyinosinic:polycytidylic acid had a similar effect as RV16 on mRNA expression of these peptides in PBEC. In line with this, PBEC were found to express TLR3, a Toll-like receptor involved in recognition of dsRNA. This study shows that rhinovirus infection of PBEC leads to increased hBD-2 and hBD-3 mRNA expression, which may play a role in both the uncomplicated common cold and in virus-associated exacerbations of asthma.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Human beta-defensins (hBDs) are antimicrobial peptides that play important roles in host defense against infection, inflammation and immunity. Previous studies showed that micro-organisms and proinflammatory mediators regulate the expression of these peptides in airway epithelial cells. The aim of the present study was to investigate the modulation of expression of hBDs in cultured primary bronchial epithelial cells (PBEC) by rhinovirus-16 (RV16), a respiratory virus responsible for the common cold and associated with asthma exacerbations. RV16 was found to induce expression of hBD-2 and -3 mRNA in PBEC, but did not affect hBD-1 mRNA. Viral replication appeared essential for rhinovirus-induced beta-defensin mRNA expression, since UV-inactivated rhinovirus did not increase expression of hBD-2 and hBD-3 mRNA. Exposure to synthetic double-stranded RNA (dsRNA) molecule polyinosinic:polycytidylic acid had a similar effect as RV16 on mRNA expression of these peptides in PBEC. In line with this, PBEC were found to express TLR3, a Toll-like receptor involved in recognition of dsRNA. This study shows that rhinovirus infection of PBEC leads to increased hBD-2 and hBD-3 mRNA expression, which may play a role in both the uncomplicated common cold and in virus-associated exacerbations of asthma.