Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

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The effect of probiotic Lactobacilli strains, inulin-type fructans and oligofructose on gene expression profiles in intestinal Caco-2 cells
Wit, N.J.W. de; Lepine, Alexia ; Boekschoten, M.V. ; Mes, J.J. - \ 2018
GSE115022 - Homo sapiens - PRJNA473527
Background: Beneficial microbes can be actors in maintaining or stimulating barrier function, and may counteract pathogen-infection. Lactobacilli are particularly recognized for enhancing intestinal barrier function and to confer protective effects against multiresistant pathogens. Various L. acidophilus strains support intestinal immune barrier function and have been shown to improve resistance to pathogens. Although less extensively studied than beneficial bacteria, other food-based ingredients that can contribute to strengthening barrier function are dietary fibers. For instance, inulin and fructooligosaccharides (FOS) have recently been shown to enhance barrier function and protect against barrier dysfunction. Effects of these ingredients on intestinal barrier function were evaluated by quantifying regulation of gene expression by microarray. Methods: Caco-2 cells were incubated with probiotic strains or inulin-type fibers for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. Results: Only L. acidophilus modulated a group of 26 genes related to tight-junctions. Inulin-type fructans, L. brevis W63 and L. casei W56 regulated other genes, unrelated to tight junctions. L. acidophilus also had unique effects on a group of 6 genes regulating epithelial phenotype towards follicle-associated epithelium. L. acidophilus W37 was therefore selected for a challenge with STM and prevented STM-induced barrier disruption and decreased secretion of IL-8. L. acidophilus W37 increases TEER and can protect against STM induced disruption of gut epithelial cells integrity in vitro. Conclusion: Our results suggest that selection of specific bacterial strains for enforcing barrier function may be a promising strategy to reduce or prevent STM infections.
Expression of protocadherin gamma in skeletal muscle tissue is associated with age and muscle weakness
Hangelbroek, R.W.J. ; Fazelzadeh, P. ; Tieland, C.A.B. ; Boekschoten, M.V. ; Hooiveld, G.J.E.J. ; Duynhoven, J.P.M. van; Timmons, James ; Verdijk, L. ; Groot, C.P.G.M. de; Loon, L.J.C. van; Müller, M.R. - \ 2018
GSE117525 - Homo sapiens - PRJNA482398
The skeletal muscle system plays an important role in the independence of older adults. In this study we examine differences in the skeletal muscle transcriptome between healthy young and older subjects and (pre‐)frail older adults. Additionally, we examine the effect of resistance‐type exercise training on the muscle transcriptome in healthy older subjects and (pre‐)frail older adults. Baseline transcriptome profiles were measured in muscle biopsies collected from 53 young, 73 healthy older subjects, and 61 frail older subjects. Follow‐up samples from these frail older subjects (31 samples) and healthy older subjects (41 samples) were collected after 6 months of progressive resistance‐type exercise training. Frail older subjects trained twice per week and the healthy older subjects trained three times per week. At baseline genes related to mitochondrial function and energy metabolism were differentially expressed between older and young subjects, as well as between healthy and frail older subjects. Three hundred seven genes were differentially expressed after training in both groups. Training affected expression levels of genes related to extracellular matrix, glucose metabolism, and vascularization. Expression of genes that were modulated by exercise training was indicative of muscle strength at baseline. Genes that strongly correlated with strength belonged to the protocadherin gamma gene cluster (r = −0.73). Our data suggest significant remaining plasticity of ageing skeletal muscle to adapt to resistance‐type exercise training. Some age‐related changes in skeletal muscle gene expression appear to be partially reversed by prolonged resistance‐type exercise training. The protocadherin gamma gene cluster may be related to muscle denervation and re‐innervation in ageing muscle.
Circadian misalignment induces fatty acid metabolism gene profiles and induces insulin resistance in human skeletal muscle
Wefers, Jakob ; Moorsel, Dirk van; Hansen, Jan ; Hooiveld, G.J.E.J. ; Kersten, A.H. ; Schrauwen, Patrick - \ 2018
GSE106800 - Homo sapiens - PRJNA418092
Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes, however, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and muscle molecular circadian clock have never been investigated in humans. Here we investigated insulin sensitivity and muscle metabolism in fourteen healthy young lean men (age 22.4 ± 2.8 years; BMI 22.3 ± 2.1 kg/m2 [mean ± SD]) after a 3-day control protocol and a 3.5-day misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that circadian misalignment results in a significant decrease in peripheral insulin sensitivity due to a reduced skeletal muscle non-oxidative glucose disposal (Rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg/min; control vs. misalignment; p=0.024). Fasting glucose and FFA levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the new behavourial rhythm, and microarray analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misallignement. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.
Pure epicatechin and inflammatory gene expression profiles in circulating immune cells in (pre) hypertensive adults; a randomized double-blind, placebo-controlled, crossover trial
Esser, D. ; Dower, J.I. ; Matualatupauw, J.C. ; Geleijnse, J.M. ; Kromhout, D. ; Hollman, P.C.H. ; Afman, L.A. - \ 2018
Homo sapiens - GSE84453 - PRJNA329219
Introduction: There is increasing evidence that consumption of cocoa products have a beneficial effect on cardio-metabolic health, but the underlying mechanisms remain unclear. Cocoa contains a complex mixture of flavan-3-ols. Epicatechin, a major monomeric flavan-3-ol, is considered to contribute to the cardio-protective effects of cocoa. We investigated effects of pure epicatechin supplementation on whole genome gene expression profiles of circulating immune cells. Methods: In a randomized, double blind, placebo-controlled cross-over trial, 37 (pre)hypertensive (40-80y) subjects received two 4-week interventions; epicatechin (100mg/day) or placebo with a wash-out period of 4-week between both interventions. Whole genome gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Results: After epicatechin supplementation 1180 genes were significantly regulated, of which 234 were also significantly regulated compared to placebo. Epicatechin supplementation up-regulated gene sets involved in transcription/translation and tubulin folding and down-regulated gene sets involved in inflammation. Only a few genes within these regulated gene sets were actually significantly changed upon epicatechin supplementation. Upstream regulators that were shown to be inhibited were classified as cytokine or inflammatory type molecules. Conclusion: Pure epicatechin supplementation modestly reduced gene expression related to inflammation signalling routes in circulating immune cells. These routes are known to play a role in cardiovascular health.
Adipose tissue gene expression is differentially regulated with different rates of weight loss in overweight and obese humans
Vink, R.G. ; Roumans, N.J. ; Fazelzadeh, Parastoo ; Tareen, S.H. ; Boekschoten, Mark ; Mariman, E.C. ; Baak, M.A. van - \ 2017
Homo sapiens - GSE77962 - PRJNA312210
Background: Moderate weight loss can ameliorate adverse health effects associated with obesity, reflected by an improved adipose tissue (AT) gene expression profile. However, the effect of rate of weight loss on the AT transcriptome is unknown.
A short-term intervention with selenium affects expression of genes implicated in the epithelial-to-mesenchymal transition in the prostate
Gils-Kok, Dieuwertje van; Kiemeney, Lambertus A.L.M. ; Verhaegh, Gerald W. ; Schalken, Jack A. ; Lin, Emile N.J.T. van; Sedelaar, J.P.M. ; Witjes, J.A. ; Hulsbergen-van de Kaa, Christina A. ; Veer, Pieter van 't; Kampman, Ellen ; Afman, Lydia - \ 2017
GSE77959 - Homo sapiens - PRJNA312203
In parallel with the inconsistency in observational studies and chemoprevention trials, the molecular mechanisms by which selenium may affect prostate cancer risk have not been elucidated. We conducted a randomized, placebo-controlled intervention trial to examine the effects of a short-term intervention with selenized yeast on whole-genome expression profiles in non-malignant prostate tissue. Twenty-three men receiving prostate biopsies were randomly assigned to take 300 µg selenized yeast per day (n=12) or placebo (non-selenized yeast, n=11) during a median intervention period of 35 (interquartile range: 31-35) days. Prostate specimens, collected from the transition zone before and after intervention, of 15 participants (n=8 selenium, n=7 placebo) were available for analysis using Affymetrix GeneChip Human 1.0 ST Arrays. Pathway and gene set enrichment analyses revealed that the intervention with selenium resulted in a down-regulated expression of genes involved in signaling pathways related to cellular adhesion, migration, invasion, remodeling and immune responses. Specifically, expression of the well-established epithelial marker E-cadherin was up-regulated, while mesenchymal markers, such as vimentin and fibronectin, were down-regulated after the intervention with selenium. This implies an effect of selenium on the epithelial-to-mesenchymal transition (EMT). Moreover, selenium affected expression of genes involved in wound healing and inflammation, processes which are both related to EMT. In conclusion, our data showed that selenium affected expression of genes implicated in EMT, mainly represented by a change in the direction of the epithelial rather than the mesenchymal phenotype.
Association between DNA methylation profiles in leukocytes and serum levels of persistent organic pollutants in Dutch men
Dungen, Myrthe van den; Murk, Tinka ; Kampman, Ellen ; Steegenga, Wilma ; Gils-Kok, Dieuwertje van - \ 2017
Homo sapiens - GSE79329 - PRJNA315514
Genome-wide DNA methylation profiling was performed in Dutch men consuming eel from relatively low- or high-polluted areas, resulting in a broad range of serum POP levels. The Illumina Infinium 450K Human DNA methylation Beadchip v1.0HD was used to measure DNA methylation in these men and associate this with serum levels of persistent organic pollutants (POPs). In total 48 POPs were measured, of which 30 POPs had levels above the detection limit in at least 60% of the participants. Furthermore, 11 different clinical parameters were measured as biomarkers for health. The leukocyte count was measured in each sample to adjust DNA methylation values. Furthermore, participants reported possible confounders in a questionnaire.
The effects of Lactobacillus plantarum on small intestinal barrier function and mucosal gene transcription; a randomized double-blind placebo controlled trial
Mujagic, Zlatan ; Vos, Paul de; Boekschoten, Mark ; Govers, Coen ; Pieters, Harm J.H.M. ; Wit, Nicole de; Bron, Peter A. ; Masclee, Ad A.M. ; Troost, Freddy J. - \ 2017
Homo sapiens - GSE74988 - PRJNA302145
The aim of this study was to investigate the effects of three Lactobacillus plantarum strains on in-vivo small intestinal barrier function and gene transcription in human subjects. The strains were selected for their differential effects on TLR signalling and tight junction protein rearrangement, which may lead to beneficial effects in a stressed human gut mucosa. Ten healthy volunteers participated in four different intervention periods: 7-day oral intake of either L. plantarum WCFS1, CIP48 (CIP104448), TIFN101 (CIP104450) or placebo, proceeded by a 4 weeks wash-out period. Lactulose-rhamnose ratio (an indicator of small intestinal permeability) increased after intake of indomethacin, which was given as an artificial stressor of the gut mucosal barrier (mean ratio 0.06±0.04 to 0.10±0.06, p=0.001), but was not significantly affected by the bacterial interventions. However, gene transcription pathway analysis in small intestinal biopsies, obtained by gastroduodenoscopy, demonstrated that particularly L. plantarum TIFN101 modulated cell-cell adhesion with high turnover of genes involved in tight- and adhesion junction protein synthesis and degradation (e.g. actinin alpha-4, metalloproteinase-2). These effects were less pronounced for L. plantarum WCFS1 and CIP104448. In conclusion, L. plantarum TIFN101 induced the most pronounced probiotic properties with specific effects on repair processes in the compromised intestine of healthy subjects.
Mining microbial metatranscriptomes for expression of antibiotic resistance genes under natural conditions
Versluis, D. ; Andrea, M.M. D'; Ramiro Garcia, J. ; Leimena, M.M. ; Hugenholtz, F. ; Zhang, J. ; Ozturk, Basak ; Nylund, L. ; Sipkema, D. ; Schaik, W. van; Vos, W.M. de; Kleerebezem, M. ; Smidt, H. ; Passel, M.W.J. van - \ 2016
PRJEB7599 - Sus scrofa - Homo sapiens - Crambe crambe - Mus musculus
We use a novel approach (an analysis of metatranscriptomics data) to study antibiotic resistance, a topic that poses major health care concerns. We investigate resistance gene expression in microbial communities in a diverse range of environments.
Macrophage heterogeneity in human carotid artery atherosclerotic plaques: identification of novel markers for M1 and M2 that are independent of the activation status
Tits, L.J. van; Stienstra, Rinke ; Netea, M.G. ; Pol, J.A. ; Truijers, M. ; Vliet, J.A. van der; Hooiveld, Guido ; Joosten, L.A. ; Stalenhoef, A.F. - \ 2016
GSE22543 - Homo sapiens - PRJNA128169
Recent studies suggest the presence of both “classically activated” M1 and “alternatively activated” M2 macrophages in human atherosclerotic tissue, yet due to the lack of validated markers the reported localization patterns of these macrophage phenotypes within plaques are ambiguous. In the present study, we searched for markers that indisputably can identify differentiated M1 and M2 macrophages independently of stimuli that affect the activation status of the two subpopulations. We used these validated markers to assess the presence of M1 and M2 macrophages in different zones of human carotid artery atherosclerotic plaques obtained from 12 patients. Using microarray and qPCR technology we show that the frequently used macrophage subpopulation markers MCP-1 and CD206 do not discriminate between M1 and M2 macrophages. However, we confirm the subtype specificity of the classical M2 marker CD163 and we report that the genes INHBA and DSP (both M1) and SEPP1 and MARCKS (both M2) are highly suitable for macrophage phenotyping. mRNA expression of the pan-macrophage marker CD68 in the shoulder zones of the plaques and in adjacent tissue segments correlated positively with mRNA expression levels of SEPP1, MARCKS and CD163 (r=0.86, 0.94 and 0.96, and r= 0.86, 0.98 and 0.69, respectively) but not with the expression of the M1 markers DSP and INHBA. In contrast, mRNA expression of CD68 in the core of the plaques correlated positively with expression of DSP and INHBA (r=0.73 and 0.49) but not with SEPP1, MARCKS and CD163. These findings suggest that M1 macrophages predominate in the core of human carotid atherosclerotic plaques while M2 macrophages prevail at the periphery of the plaque.
Innate Immune Recognition of Bacterial Viability Instructs Human T follicular Helper Cell Differentiation
Valai, Atijeh ; Ugolini, Matteo ; Gerhard, Jenny ; Georg, Philipp ; Helbig, Elisa T. ; Opitz, Bastian ; Kurth, Florian ; Boekschoten, Mark ; Muller, Michael ; Suttorp, Norbert ; Sander, Leif E. - \ 2016
GSE68255 - Homo sapiens - PRJNA282140
Live attenuated vaccines are often superior to dead vaccines, yet the immunological mechanisms remain largely obscure. We have recently uncovered an inherent capacity of antigen-presenting cells (APC) to discriminate live from killed bacteria by virtue of vita-PAMPs. Here we found that innate recognition of bacterial viability strongly promotes the differentiation of fully functional T follicular helper (TFH) cells. We identify TLR8 and its signaling adaptor MyD88 as critical sensor for bacterial viability in human APC, activation of which is required and sufficient to induce selective transcriptional remodeling and the production of TFH promoting signals like IL-12. Activators of other TLRs including licensed vaccine adjuvants fail to do so. Consequently, vita-PAMP receptors such as TLR8 represent promising targets for adjuvants to improve the efficacy of modern inanimate subunit vaccines.
Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid
IJssenagger, N. ; Janssen, A.W.F. ; Kersten, A.H. ; Mil, S.W.C. van - \ 2016
Homo sapiens - Mus musculus - GSE76163 - PRJNA306501
This SuperSeries is composed of the SubSeries listed below.
Gene expression profiling in human precision-cut liver slices upon treatment with the FXR agonist obeticholic acid [human]
IJssennagger, Noortje ; Janssen, Aafke ; Mil, Saskia van; Kersten, Sander - \ 2016
GSE76161 - Homo sapiens - PRJNA306505
Background: The bile acid-activated farnesoid X receptor (FXR) is a nuclear receptor regulating bile acid, glucose and cholesterol homeostasis. Obeticholic acid (OCA; also known as INT-747 or 6α-ethyl-chenodeoxycholic acid), a promising drug for the treatment of non-alcoholic steatohepatitis (NASH) and type 2 diabetes, activates FXR. Mouse studies demonstrated that FXR activation by OCA (INT-747) alters hepatic expression of many genes. However, no data are available on the effects of OCA in human liver. Here, we generated gene expression profiles in human precision-cut liver slices (hPCLS) after treatment with OCA.
Different pathogenic stimuli induce specific metabolic rewiring in human monocytes
Lachmandas, Ekta ; Boutens, Lily ; Ratter, Jacqueline ; Hijmans, Anneke ; Hooiveld, Guido ; Crevel, Reinout van; Netea, Mihai ; Stienstra, Rinke - \ 2016
Homo sapiens - GSE78699 - PRJNA313233
Recent studies have demonstrated that upon encountering a pathogenic stimulus, robust metabolic rewiring of immune cells occurs. A switch away from oxidative phosphorylation to glycolysis, even in the presence of sufficient amounts of oxygen (akin the Warburg effect), is typically observed in activated innate and adaptive immune cells and is thought to accommodate adequate inflammatory responses. However, whether the Warburg effect is a general phenomenon applicable in human monocytes exposed to different pathogenic stimuli is unknown. Our results using human monocytes from healthy donors demonstrate that the Warburg effect only holds true for TLR4 activated cells. Although activation of other TLRs leads to an increase in glycolysis, no reduction or even an enhancement in oxidative phosphorylation is observed. Moreover, specific metabolic rewiring occurs in TLR4 vs. TLR2 stimulated cells characterized by altered gene expression profiles of pathways related to metabolism, changes in spare respiratory capacity of the cells and differential regulation of mitochondrial enzyme activity. Similarly, results from ex vivo and in vivo studies demonstrate metabolic rewiring of immune cells that is highly dependent on the type of pathogenic stimulus. Although the Warburg effect is observed in human monocytes after TLR4 activation, we propose that this typical metabolic response is not applicable to other inflammatory signalling routes including TLR2 in human monocytes. Instead, each pathogenic stimulus and subsequently activated inflammatory signalling cascade induces specific metabolic rewiring of the immune cell to accommodate an appropriate response.
Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: a Randomized Double-blind Placebo-controlled Trial
Reijnders, Dorien ; Goossens, Gijs H. ; Neis, Evelien P.J.G. ; Beek, Christina M. van der; Most, Jasper ; Holst, Jens J. ; Lenaerts, Kaatje ; Kootte, Ruud S. ; Nieuwdorp, Max ; Groen, Albert K. ; Boekschoten, Mark ; Hermes, Gerben ; Smidt, Hauke ; Zoetendal, Erwin ; Dejong, Cornelis H.C. ; Blaak, Ellen E. - \ 2016
Homo sapiens - GSE76003 - PRJNA305937
The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans.
Comprehensive DNA methylation and gene expression profiling in differentiating human adipocytes
Dungen, Myrthe van den; Murk, Tinka ; Gils-Kok, Dieuwertje van; Steegenga, Wilma - \ 2016
GSE74609 - Homo sapiens - PRJNA300955
Genome-wide DNA methylation profiling was performed of human mesenchymal stem cells (hMSCs) differentiating into adipocytes (day 10). The Illumina Infinium 450k Human DNA methylation Beadchip v1.2 was used to measure DNA methylation of hMSC before differentiation (day 0) and of adipocytes at day 10 of differentiation. Our aims were to 1) measure genome-wide DNA methylation changes during adipocyte differentiation in primary hMSCs and 2) investigate the relationship between DNA methylation and gene expression regulation in a panel of 84 adipocyte-related genes.
Persistent organic pollutants alter DNA methylation during human adipocyte differentiation
Dungen, Myrthe van den; Murk, Tinka ; Steegenga, Wilma ; Gils-Kok, Dieuwertje van - \ 2016
Homo sapiens - GSE75133 - PRJNA302608
Genome-wide DNA methylation profiling was performed in human mesenchymal stem cells (hMSCs) differentiated into adipocytes (day 10) while being continuously exposed to either one of three different persistent organic pollutants (POPs), namely TCDD, PFOS, and TBT. The Illumina Infinium 450K Human DNA methylation Beadchip v1.2 was used to measure DNA methylation of unexposed differentiated adipocytes and compared to POP-exposed differentiated adipocytes. Our aims were to 1) measure genome-wide DNA methylation changes upon POP exposure during adipocyte differentiation in primary hMSCs and 2) investigate the relationship between DNA methylation and gene expression regulation after POP-exposure in a panel of 84 adipocyte-related genes.
Differences in genome-wide gene expression response in PBMCs between young and old men upon caloric restriction
Bussel, I.P.G. van; Stoppelenburg, J.A. ; Groot, C.P.G.M. de; Müller, M.R. ; Afman, L.A. - \ 2016
Homo sapiens - GSE63117 - PRJNA266659
Caloric restriction (CR) is considered to increase lifespan and to prevent various age-related diseases in different non-human organisms. Only a limited number of CR studies have been performed in humans, and results put CR as a beneficial tool to decrease risk factors in several age-related diseases. The question remains at what age CR should be implemented to be most effective with respect to healthy aging. The aim of our study was to elucidate the role of age in the transcriptional response to a 30% CR diet in immune cells, as immune response is affected during aging. Ten healthy young men, aged 20-34, and nine healthy old men, aged 64-85, were subjected to a two week weight maintenance diet, followed by three weeks of 30% CR. Before and after 30% CR, peripheral blood mononuclear cells’ (PBMCs) whole genome gene expression was assessed. Expression of 554 genes showed a different response between young and old men upon CR. Gene set enrichment analysis revealed a downregulation of gene sets involved in immune response in young men, but not in old men. At baseline, immune response-related genes were already higher expressed in old compared to young men. Upstream regulator analyses revealed that most potential regulators were controlling immune response, and were inhibited in young men upon CR, and activated in old men at baseline. Based on the gene expression data, we conclude that a short period of CR is more effective in young men compared to old men regarding immune related pathways.
The effect of onion exposure on gene expression profiles in intestinal Caco-2 cells
Wit, N.J.W. de; Govers, C.C.F.M. ; Boekschoten, M.V. ; Mes, J.J. - \ 2016
Homo sapiens - GSE83893 - PRJNA327311
Background: Human intestinal tissue samples are barely accessible to study potential health benefits of nutritional compounds. Numbers of animals used in animal trials, however, need to be minimalized. Therefore, in this study we explored the applicability of an in vitro model, namely human intestinal Caco-2 cells, to study the effect of food compounds on (intestinal) health. In vitro digested yellow (YOd) and white onion extracts (WOd) were used as model food compounds and transcriptomics was applied to obtain more insight into their mode of actions in the intestinal cells. Methods: Caco-2 cells were incubated with in vitro digested onion extracts for 6 hours, total RNA was extracted and Affymterix Human Gene 1.1 ST arrays were used to analyze the gene expression profiles. To identify onion-induced gene expression profiles in Caco-2 cells, digested yellow onion and white onion samples were compared to a digest control samples. Results: We found that yellow onion (n=5586, p<0.05) had a more pronounced effect on gene expression than white onion (n=3688, p<0.05). However, a substantial number of genes (n=3281, p<0.05) were affected by both onion variants in the same direction. Pathway analyses revealed that mainly processes related to oxidative stress, and especially the Keap1-Nrf2 pathway, were affected by onions. Our data fit with previous in vivo studies showing that the beneficial effects of onions are mostly linked to their antioxidant properties. Conclusion: our data indicate that the in vitro Caco-2 intestinal model can be used to determine modes of action of nutritional compounds and can thereby reduce the number of animals used in conventional nutritional intervention studies.
Different responses of Caco-2 and MCF-7 cells to silver nanoparticles are based on highly similar mechanisms of action
Zande, M. van der; Undas, A.K. ; Kramer, E.H.M. ; Monopoli, Marco P. ; Peters, R.J.B. ; Garry, David ; Antunes Fernandes, E.C. ; Hendriksen, P.J.M. ; Marvin, H.J.P. ; Peijnenburg, A.A.C.M. ; Bouwmeester, H. - \ 2016
Homo sapiens - GSE84982 - PRJNA335824
The mode of action of silver nanoparticles (AgNPs) is suggested to be exerted through both Ag+ and AgNP dependent mechanisms. Ingestion is one of the major NP exposure routes, and potential effects are often studied using Caco-2 cells, a well-established model for the gut epithelium. MCF-7 cells are epithelial breast cancer cells with extensive well-characterized toxicogenomics profiles. In the present study we aimed to gain a deeper understanding of the cellular molecular responses in Caco-2 and MCF-7 cells after AgNP exposure in order to evaluate whether epithelial cells derived from different tissues demonstrated similar responses. These insights could possibly reduce the size of cell panels for NP hazard identification screening purposes. AgNPs of 20, 30, 60, and 110 nm, and AgNO3 were exposed for 6h and 24h. AgNPs were shown to be taken up and dissolve intracellularly. Compared with MCF-7 cells, Caco-2 cells showed a higher sensitivity to AgNPs, slower gene expression kinetics, and absence of NP size-dependent responses. However, on a molecular level, no significant differences were observed between the two cell types. Transcriptomic analysis showed that Ag(NP) exposure caused (oxidative) stress responses, possibly leading to cell death in both cell lines. There was no indication for effects specifically induced by AgNPs. Responses to AgNPs appeared to be induced by silver ions released from the AgNPs. In conclusion, differences in mRNA responses to AgNPs between Caco-2 and MCF-7 cells were mainly related to timing and magnitude, but not to a different underlying mechanism.
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