Éditeur(s) : HAL CCSD BioMed Central
Résumé : International audience
BACKGROUND: The aryl hydrocarbon receptor (AhR) has gradually emerged as a regulator of inflammation in the lung and other tissues. AhR may interact with the p65-subunit of the nuclear factor (NF)-κB transcription factors, but reported outcomes of AhR/NF-κB-interactions are conflicting. Some studies suggest that AhR possess pro-inflammatory activities while others suggest that AhR may be anti-inflammatory. The present study explored the impact of AhR and its binding partner AhR nuclear translocator (Arnt) on p65-activation and two differentially regulated chemokines, CXCL8 (IL-8) and CCL5 (RANTES), in human bronchial epithelial cells (BEAS-2B). RESULTS: Cells were exposed to CXCL8- and CCL5-inducing chemicals, 1-nitropyrene (1-NP) and 1-aminopyrene (1-AP) respectively, or the synthetic double-stranded RNA analogue, polyinosinic-polycytidylic acid (Poly I:C) which induced both chemokines. Only CXCL8, and not CCL5, appeared to be p65-dependent. Yet, constitutively active unligated AhR suppressed both CXCL8 and CCL5, as shown by siRNA knock-down and the AhR antagonist α-naphthoflavone. Moreover, AhR suppressed activation of p65 by TNF-α and Poly I:C as assessed by luciferase-assay and p65-phosphorylation at serine 536, without affecting basal p65-activity. In contrast, Arnt suppressed only CXCL8, but did not prevent the p65-activation directly. However, Arnt suppressed expression of the NF-κB-subunit RelB which is under transcriptional regulation by p65. Furthermore, AhR-ligands alone at high concentrations induced a moderate CXCL8-response, without affecting CCL5, but suppressed both CXCL8 and CCL5-responses by Poly I:C. CONCLUSION: AhR and Arnt may differentially and independently regulate chemokine-responses induced by both inhaled pollutants and pulmonary infections. Constitutively active, unligated AhR suppressed the activation of p65, while Arnt may possibly interfere with the action of activated p65. Moreover, ligand-activated AhR suppressed CXCL8 and CCL5 responses by other agents, but AhR ligands alone induced CXCL8 responses when given at sufficiently high concentrations, thus underscoring the duality of AhR in regulation of inflammation. We propose that AhR-signaling may be a weak activator of p65-signaling that suppresses p65-activity induced by strong activators of NF-κB, but that its anti-inflammatory properties also are due to interference with additional pathways.
ISSN: 1478-811X

inserm-01085082
http://www.hal.inserm.fr/inserm-01085082
http://www.hal.inserm.fr/inserm-01085082/document
http://www.hal.inserm.fr/inserm-01085082/file/s12964-014-0048-8.pdf
PUBMED : 25201625

Éditeur(s) : Public Library Science
Résumé : Like hydrothermal vents along oceanic ridges, cold seeps are patchy and isolated ecosystems along continental margins, extending from bathyal to abyssal depths. The Atlantic Equatorial Belt (AEB), from the Gulf of Mexico to the Gulf of Guinea, was one focus of the Census of Marine Life ChEss (Chemosynthetic Ecosystems) program to study biogeography of seep and vent fauna. We present a review and analysis of collections from five seep regions along the AEB: the Gulf of Mexico where extensive faunal sampling has been conducted from 400 to 3300m, the Barbados accretionary prism, the Blake ridge diapir, and in the Eastern Atlantic from the Congo and Gabon margins and the recently explored Nigeria margin. Of the 72 taxa identified at the species level, a total of 9 species or species complexes are identified as amphi-Atlantic. Similarity analyses based on both Bray Curtis and Hellinger distances among 9 faunal collections, and principal component analysis based on presence/absence of megafauna species at these sites, suggest that within the AEB seep megafauna community structure is influenced primarily by depth rather than by geographic distance. Depth segregation is observed between 1000 and 2000m, with the middle slope sites either grouped with those deeper than 2000m or with the shallower sites. The highest level of community similarity was found between the seeps of the Florida escarpment and Congo margin. In the western Atlantic, the highest degree of similarity is observed between the shallowest sites of the Barbados prism and of the Louisiana slope. The high number of amphi-atlantic cold-seep species that do not cluster according to biogeographic regions, and the importance of depth in structuring AEB cold-seep communities are the major conclusions of this study. The hydrothermal vent sites along the Mid Atlantic Ridge (MAR) did not appear as "stepping stones" for dispersal of the AEB seep fauna, however, the south MAR and off axis regions should be further explored to more fully test this hypothesis.
Plos One (1932-6203) (Public Library Science), 2010-08 , Vol. 5 , N. 8 , P. 1-11

Droits : © 2010 Olu et al.
http://archimer.ifremer.fr/doc/00011/12207/8975.pdf
DOI:10.1371/journal.pone.0011967
http://archimer.ifremer.fr/doc/00011/12207/

Éditeur(s) : Gauthier-Villars
Résumé : Preparative pyrolysis followed by liquid chromatographic separation and gas chromatography of hydrocarbons (Pyrolysis-LC-GC) were used to study the participation of terrestrial and/or aquatic compounds in the formation of humic substances in sediments. Analyses performed on humic substances from recent sediments sampled in the Elorn river estuary (France) show that these substances are similar in many respects to other lacustrine or marine humic substances, with regard, for instance, to their high nitrogen and sulphur content and their low aromaticity. Mass balances on pyrolysis products and group composition of the C-14+ fraction of the pyrolysates were performed. The distribution of the total alkane and alkene fraction, isocyclo alkanes and alkenes from these humic acid pyrolysates was compared to that of various reference humic acid pyrolysates. The biomarker study (distribution and hopanes/steranes ratios from humic acid pyrolysates) confirms the participation throughout the estuary of algal precursors in the formation of the studied compounds, irrespective of the location of the sampling zone (upstream, median or downstream part of the estuary).
Oceanologica Acta (0399-1784) (Gauthier-Villars), 1994 , Vol. 17 , N. 1 , P. 43-53

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00099/21029/18655.pdf
http://archimer.ifremer.fr/doc/00099/21029/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
In petroleum industry, the difference between pore pressure (Pp) and minimum horizontal stress Sh (termed the seal or retention capacity) is of major consideration because it is often assumed to represent how close a system is to hydraulic failure and thus the maximum hydrocarbon column height that can be maintained. While Sh and Pp are often considered to be independent parameters, several studies in the last decade have demonstrated that Sh and Pp are in fact coupled. However, the nature of this coupling relationship remains poorly understood. In this paper, we explore the influences of the spatial pore pressure distribution on Sh/Pp coupling and then on failure pressure predictions and trap integrity evaluation. With analytical models, we predict the fluid pressure sustainable within a reservoir before failure of its overpressured shale cover. We verify our analytical predictions with experiments involving analogue materials and fluids. We show that hydraulic fracturing and seal breach occur for fluid pressure greater than it would be expected from conventional retention capacity. This can be explained by the impact of the fluid overpressure field in the overburden and the pressure diffusion around the reservoir on the principal stresses. We calculate that supralithostatic pressure could locally be reached in overpressured covers. We also define the retention capacity of a cover (RC) surrounding a fluid source or reservoir as the difference between the failure pressure and the fluid overpressure prevailing in shale at the same depth. In response to a localized fluid pressure rise, we show that the retention capacity does not only depend on the pore fluid overpressure of the overburden but also on the tensile strength of the cover, its Poisson's ratio, and the depth and width of the fluid source.
ISSN: 0264-8172

hal-00590497
https://hal.archives-ouvertes.fr/hal-00590497
DOI : 10.1016/j.marpetgeo.2010.08.007

Éditeur(s) : Gauthier-Villars
Résumé : The analysis of humic compounds by elemental analysis, PY-GC-MS and HPLC techniques permitted determination of the origin of organic inputs, essentially terrestrial, and the effects of environmental conditions in the deposits along a north-south transect through the Rhone delta, from the river mouth to the open sea. In the prodelta the sedimentation of fine particles enriches the sediments in organic matter. The humic compound contents were relatively low in sediments, perhaps due to a rapid burying of organic matter which leads to anoxic conditions. In sediments fulvic acids are more abundant than humic acids. Elemental analysis indicated that fulvic acids were enriched in hydrogen and nitrogen as compared to humic acids. Furthermore, H/C and N/C ratios increased in the fulvic and humic acids towards the open sea, related to a more marine character. Pyrolysis analysis showed some differences between the chemical composition of fulvic acids which correspond to low molecular weights enriched in carbohydrates, and that of humic acids, high molecular weight compounds which are enriched in phenols and aromatic hydrocarbons. The pyrolysis-derived phenols were abundant near the river mouth, decreasing towards the open sea as nitrogen-containing-compounds increased. Near the river mouth, the abundance of phenolic aldehydes demonstrated by HPLC emphasized the existence of fresh organic matter. On the other hand, off the mouth, an increase in phenolic acids could indicate a more degraded organic material. The fractionation of humic acids in various classes of molecular weight species using ultrafiltration (Amicon membranes) and their analysis showed that, close to the river mouth, the large proportion of the high molecular weight humic compounds observed was enriched in phenols and carbohydrates, probably inherited from the terrestrial ligno-cellulosic complex. This process seemed to be superimposed on the increase of molecular weights which is usually observed as the environment becomes purely marine. These humic compounds would derived either from organic matter from terrestrial soils swept along by the river flow, after deposition on its bed or, more probably, from high molecular weight compounds which, associated with the mineral phase, flocculated when reaching the fluvio-marine front. Generally, the low molecular weight fractions were enriched in hydrogen and nitrogen. Near the river mouth, nitrogen-containing compounds were concentrated in the low molecular weight classes which correspond to organic molecules regarded as humic precursors. Off the mouth, they were incorporated into the high molecular weight complexes, certainly of marine origin.
Oceanologica Acta (0399-1784) (Gauthier-Villars), 1992 , Vol. 15 , N. 1 , P. 61-74

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00101/21187/18804.pdf
http://archimer.ifremer.fr/doc/00101/21187/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
People are exposed to multiple pollutants, especially indoors, in particular through ingestion of indoor settled dust. In the perspective of a cumulative risk assessment, a multi-residue analytical method based on pressurized liquid extraction (PLE) and gas chromatography/tandem mass spectrometry (GC/MS/MS) was developed for the simultaneous analysis in indoor dust of several classes of semi-volatile organic compounds (SVOCs) of health concern, from trace to highly concentrated compounds, including musk fragrances, organochlorines (OCs), organophosphates (OPs), polycyclic aromatic hydrocarbons (PAHs), polybromodiphenylethers (PBDEs), polychlorobiphenyls (PCBs), phthalates and pyrethroids. The method was validated in terms of limits of quantification (LOQ), and accuracy and precision via spiking experiments on an inert material (Celite(®) 545) and replicate analysis of the standard reference material SRM 2585 supplied by the National Institute of Standards and Technology (NIST). Method LOQs for 200 mg samples of sieved dust were 26 ng g(-1) for PCBs and some OCs, 65 ng g(-1) for musks, OPs, PAHs, PBDEs, pyrethroids, other OCs and some phthalates, 132 ng g(-1) for butylbenzylphthalate (BBP), 197 ng g(-1) for tributylphosphate and 1579 ng g(-1) for other phthalates. Quadratic calibration curves were established for each compound by analyzing at least five calibration solutions and exhibited determination coefficients higher than 0.999. The method was successfully applied to the SRM 2585 and seven real indoor dust samples. The results obtained on SRM 2585 demonstrate both excellent reproducibility and agreement with the indicative, reference or certified values and provide, for the first time, indicative concentrations for chlorpyrifos, diazinon, diisononylphthalate (DiNP) and tetramethrin. The results obtained on real dust samples illustrate the ability of the proposed method to quantify a wide range of SVOCs in a single analysis, making it appropriate for environmental monitoring programs or large-scale studies with a large number of samples.
ISSN: 0021-9673

hal-00994493
https://hal-univ-rennes1.archives-ouvertes.fr/hal-00994493
DOI : 10.1016/j.chroma.2014.02.004
PUBMED : 24598454

Éditeur(s) : HAL CCSD Karger
Résumé : International audience
BACKGROUND: Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are ubiquitous toxic environmental pollutants capable of inducing cell death. Intracellular pH plays a key role in the regulation of cell survival and death. Our previous works have demonstrated that intracellular alkalinization mediated by Na(+)/H(+) exchanger 1 (NHE-1) is a critical event involved in B[a]P-induced apoptosis. The aim of this study was to further elucidate the mechanisms of NHE-1 activation upon B[a]P exposure. METHODS: We tested the effects of plasma membrane cholesterol enrichment or depletion on B[a]P-induced NHE-1 activation related to apoptosis. We isolated cholesterol-rich plasma membrane microdomains to assess NHE-1 submembrane location and immunoprecipitated NHE-1 from the different sub-membrane fractions obtained to examine NHE-1 protein interactions during B[a]P-induced apoptosis. RESULTS: We found that NHE-1 is preferentially located in cholesterol-rich microdomains and that B[a]P activates NHE-1 via its relocation and binding of calmodulin outside these specialized plasma membrane microstructures; these events are necessary for the execution of the apoptosis-related intracellular alkalinization. CONCLUSION: Plasma membrane location of NHE-1 affects its protein interactions and apoptotic function.
ISSN: 1015-8987

inserm-00871487
http://www.hal.inserm.fr/inserm-00871487
http://www.hal.inserm.fr/inserm-00871487/document
http://www.hal.inserm.fr/inserm-00871487/file/NHE-1_Relocation_Outside_Cholesterol.accepted.pdf
DOI : 10.1159/000171027

Éditeur(s) : HAL CCSD MDPI
Résumé : International audience
The issue of drinking water quality compliance in small and medium scale water services is of paramount importance in relation to the 98/83/CE European Drinking Water Directive (DWD). Additionally, concerns are being expressed over the implementation of the DWD with respect to possible impacts on water quality from forecast changes in European climate with global warming and further anticipated reductions in north European acid emissions. Consequently, we have developed a decision support system (DSS) named ARTEM-WQ (AwaReness Tool for the Evaluation and Mitigation of drinking Water Quality issues resulting from environmental changes) to support decision making by small and medium plant operators and other water stakeholders. ARTEM-WQ is based on a sequential risk analysis approach that includes consideration of catchment characteristics, climatic conditions and treatment operations. It provides a holistic evaluation of the water system, while also assessing human health risks of organic contaminants potentially present in treated waters (steroids, pharmaceuticals, pesticides, bisphenol-a, polychlorobiphenyls, polycyclic aromatic hydrocarbons, petrochemical hydrocarbons and disinfection by-products; n = 109). Moreover, the system provides recommendations for improvement while supporting decision making in its widest context. The tool has been tested on various European catchments and shows a promising potential to inform water managers of risks and appropriate mitigative actions. Further improvements should include toxicological knowledge advancement, environmental background pollutant concentrations and the assessment of the impact of distribution systems on water quality variation.
ISSN: 1660-4601

hal-01122233
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01122233
PUBMED : 25046634
DOI : 10.3390/ijerph110707354
PUBMEDCENTRAL : PMC4113881

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are widely distributed environmental contaminants exerting toxic effects such as genotoxicity and carcinogenicity, mainly associated with aryl hydrocarbon receptor (AhR) activation and the subsequent induction of cytochromes P-450 (CYP) 1-metabolizing enzymes. We previously reported an up-regulation of AhR expression and activity in primary cultures of human T lymphocyte by a physiological activation. Despite the suggested link between exposure to PAHs and the risk of lymphoma, the potential of activated human T lymphocytes to metabolize AhR exogenous ligands such as B[a]P, and produce DNA damage has not been investigated. In the present study, we characterized the genotoxic response of primary activated T lymphocytes to B[a] P. We demonstrated that, following T lymphocyte activation, B[a]P treatment triggers a marked increase in CYP1 expression and activity generating, upon metabolic activation, DNA adducts and double-strand breaks (DSBs) after a 48-h treatment. At this time point, B[a]P also induces a DNA damage response with ataxia telangiectasia mutated kinase activation, thus producing a p53-dependent response and T lymphocyte survival. B[a]P activates DSB repair by mobilizing homologous recombination machinery but also induces gene mutations in activated human T lymphocytes which could consequently drive a cancer process. In conclusion, primary cultures of activated human T lymphocytes represent a good model for studying genotoxic effects of environmental contaminants such as PAHs, and predicting human health issues.
ISSN: 0006-2952

hal-01560145
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560145/file/Liamin%20et%20al.%20-%20Benzo%5Ba%5Dpyrene-induced%20DNA%20damage%20associated%20with%20.pdf
DOI : 10.1016/j.bcp.2017.04.025

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Polygonal faulting is a widespread phenomenon in sedimentary basins worldwide. It changes basin-scale fluid flow patterns and alters the physical properties of the sediments making it important for hydrocarbon exploration and geohazard analysis. It is generally accepted that polygonal fault patterns derive from dewatering and compaction of the host sediments, but there is debate regarding the processes that control polygonal faulting. New multibeam-bathymetry data from the Hatton Basin, NE Atlantic, show up to 10 m deep and 200-600 m wide troughs at the seabed. They connect to each other forming polygons that are several hundred metres across, i.e. of similar size as buried polygonal fault systems observed in 3D seismic data. The troughs are symmetrical and resemble elongated pockmarks. Previously unpublished high-resolution 2D seismic data from the same area show seismic disturbance zones similar to pipes observed under pockmarks elsewhere as well as faults that have all the characteristics of polygonal fault systems. The observation of the wide disturbance zones is enigmatic, as they appear to follow the polygonal seafloor pattern. The observed extent of the polygonal sediment contraction system is substantial covering almost 37,000 km2. We calculate that some 2600 km3 of possibly carbon-bearing fluids have been expelled from this system and we expect that this will affect the benthic ecosystems, although so far there is only limited evidence for chemosynthetic habitats.
ISSN: 0025-3227

hal-00772468
https://hal.archives-ouvertes.fr/hal-00772468
DOI : 10.1016/j.margeo.2012.09.013

Éditeur(s) : Gauthier-Villars
Résumé : Mud fields located In the inner part of shelves in front of large estuaries are preferential environments for the investigation of the mechanisms and evolution in time of the supply of such sedimentary bodies. The study of different constituents of the particulate organic matter trapped in the sediments of the West Gironde mud patch contributes to the knowledge of the input origins. This study was carried out with different techniques, including pyrolysis-gas chromatography-mass spectrometry and high performance liquid chromatography, on samples from a core collected in the centre of the mud field. At the bottom of the core, the increase of sugars, amino-sugars and some aromatic hydrocarbons may indicate a more marine character of organic components. The same appears to be the case at the top of the core, where, despite a finer sedimentation, biochemical characteristics could show a more pronounced marine influence than in the middle part. In the middle part of the core, on the other hand, the increase in phenols could result from an increase in lignin-derived. terrestrial inputs. The increase in pyrolysis-derived cyclopentenone may indicate the same terrestrial influence, because this component has its origin in aliphatic polycarboxylic acids resulting from sail leaching. The continental character of the sedimentation is also reflected in the increase of the silt-clay fractions representative of suspended matter originating in the Gironde estuary, associated with a slight carbonate decrease. The taxonomic significance of some phenols is noteworthy: this is especially the case of the cinnamyls which, in the middle part of the core, emphasize the input of herbaceous debris and of the hydroxybenzyls which, at the bottom, provide evidence of the algal origin of part of the organic material. Thus, by means of pyrolysis results and HPLC phenol analysis, it is possible to establish the more or less continental signature of organic components trapped in the ''Ouest-Gironde'' mud patch. This study of organic matter, which confirms earlier sedimentological and micropaleontological data, constitutes a new approach, adapted to the identification of the origin of carbon sources.
Oceanolica Acta (0399-1784) (Gauthier-Villars), 1997 , Vol. 20 , N. 5 , P. 687-695

Droits : info:eu-repo/semantics/openAccess
http://archimer.ifremer.fr/doc/00093/20426/18093.pdf
http://archimer.ifremer.fr/doc/00093/20426/

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
The heterodimeric L-type amino acid transporter (LAT) 1/ CD98hc is overexpressed in lung cancers with a poor prognosis factor. Factors that contribute to LAT1/CD98hc overexpression in lung cells remain however to be determined, but the implication of atmospheric pollution can be suspected. The present study was therefore designed to analyze the effects of diesel exhaust particle (DEP) extract (DEPe) on LAT1/CD98hc expression in bronchial epithelial BEAS-2B cells. Exposure to DEPe up-regulated LAT1 and CD98hc mRNA levels in a concentration-dependent manner, with DEPe EC50 values (around 0.2 μg/mL) relevant to environmental situations. DEPe concomitantly induced LAT1/CD98hc protein expression and LAT1-mediated leucine accumulation in BEAS-2B cells. Inhibition of the aryl hydrocarbon receptor (AhR) pathway through the use of a chemical AhR antagonist or the siRNA-mediated silencing of AhR expression was next found to prevent DEPe-mediated induction of LAT1/CD98hc, indicating that this regulation depends on AhR, known to be activated by major chemical DEP components like polycyclic aromatic hydrocarbons. DEPe exposure was finally shown to induce mRNA expression and activity of matrix metalloproteinase (MMP)-2 in BEAS-2B cells, in a CD98hc/focal adhesion kinase (FAK)/extracellular regulated kinase (ERK) manner, thus suggesting that DEPe-mediated induction of CD98hc triggers activation of the integrin/FAK/ERK signaling pathway known to be involved in MMP-2 regulation. Taken together, these data demonstrate that exposure to DEPe induces functional overexpression of the amino acid transporter LAT1/CD98h in lung cells. Such a regulation may participate to pulmonary carcinogenic effects of DEPs, owing to the well-documented contribution of LAT1 and CD98hc to cancer development.
ISSN: 0041-008X

hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01237095/file/Aryl%20hydrocarbon%20receptor-dependent%20up-regulation_accepted.pdf
DOI : 10.1016/j.taap.2015.11.014

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Nitro-polycyclic aromatic hydrocarbons (nitro-PAHs) are widespread environmental pollutants, generated from reactions between PAHs and nitrogen oxides during combustion processes. In the present study we have investigated the mechanisms of CXCL8 (IL-8) responses induced by 1-nitropyrene (1-NP) in human bronchial epithelial BEAS-2B cells, with focus on the possible importance of Ca(2+)-signaling and activation of β2-adrenergic receptors (β2AR). Ca(2+)-chelator treatment obliterated 1-NP-induced CXCL8 (IL-8) responses. 1-NP at 10μM (but not 1μM) induced a rapid and sustained increase in intracellular Ca(2+)-levels ([Ca(2+)]i). The early but not the later, sustained phase of 1-NP-induced [Ca(2+)]i was suppressed by beta-blocker treatment (carazolol). Moreover, inhibition of β2AR by blocking-antibody, beta-blocker treatment (ICI 118551) or siRNA transfection attenuated CXCL8 responses induced by 1-NP. The results confirm that PAHs may induce Ca(2+)-signaling also in BEAS-2B cells, at least partly through activation of β2AR, and suggest that both β2AR- and Ca(2+)-signaling may be involved in 1-NP-induced CXCL8 responses in bronchial epithelial cells.
ISSN: 0887-2333

hal-01058607
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01058607
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01058607/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01058607/file/Calcium_Signaling_and_I_2-Adrenergic_Receptors-final.pdf
DOI : 10.1016/j.tiv.2014.05.012

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
Diesel exhaust particles (DEPs) are common environmental air pollutants primarily affecting the lung. DEPs or chemicals adsorbed on DEPs also exert extra-pulmonary effects, including alteration of hepatic drug detoxifying enzyme expression. The present study was designed to determine whether organic DEP extract (DEPe) may target hepatic drug transporters that contribute in a major way to drug detoxification. Using primary human hepatocytes and transporter-overexpressing cells, DEPe was first shown to strongly inhibit activities of the sinusoidal solute carrier (SLC) uptake transporters organic anion-transporting polypeptides (OATP) 1B1, 1B3 and 2B1 and of the canalicular ATP-binding cassette (ABC) efflux pump multidrug resistance-associated protein 2, with IC50 values ranging from approximately 1 to 20 μg/mL and relevant to environmental exposure situations. By contrast, 25 μg/mL DEPe failed to alter activities of the SLC transporter organic cation transporter (OCT) 1 and of the ABC efflux pumps P-glycoprotein and bile salt export pump (BSEP), whereas it only moderately inhibited those of sodium taurocholate co-transporting polypeptide and of breast cancer resistance protein (BCRP). Treatment by 25 μg/mL DEPe was next demonstrated to induce expression of BCRP at both mRNA and protein level in cultured human hepatic cells, whereas it concomitantly repressed mRNA expression of various transporters, including OATP1B3, OATP2B1, OCT1 and BSEP. Such changes in transporter expression were found to be highly correlated to those caused by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a reference activator of the aryl hydrocarbon receptor (AhR) pathway. This suggests that DEPe, which is enriched in known ligands of AhR like polycyclic aromatic hydrocarbons, alters drug transporter expression via activation of the AhR cascade. Taken together, these data established human hepatic transporters as targets of organic chemicals containing in DEPs, which may contribute to their systemic effects through impairing hepatic transport of endogenous compound or drug substrates of these transporters.
ISSN: 1932-6203

Droits : http://creativecommons.org/licenses/by/
hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01138535/file/Regulation%20of%20human%20hepatic%20drug.pdf
DOI : 10.1371/journal.pone.0121232

Éditeur(s) : HAL CCSD Taylor & Francis
Résumé : International audience
INTRODUCTION: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor historically known for regulating expression of several important drug-detoxifying proteins. Besides drug metabolism pathways, cytokines have been recently recognized as targeted by the AhR signaling cascade, which may contribute to toxicity and changes in xenobiotic detoxification caused by AhR agonists. AREAS COVERED: This article summarizes the nature of the main cytokines regulated by AhR ligands and reviews their involvement in toxic effects of AhR ligands, especially in relation with inflammation. The article also discusses the potential implications for drug detoxification pathways. EXPERT OPINION: Even if various cytokines, including inflammatory ones, have already been demonstrated to constitute robust targets for AhR, the exact role played by AhR with respect to inflammation remains to be determined. Further studies are also required to better characterize the molecular mechanisms implicated in regulation of cytokines by AhR ligands and to determine the role that may play AhR-targeted cytokines in alteration of xenobiotic detoxification. Finally, changes in cytokine receptor expression triggered by AhR ligands have additionally to be taken into account to better and more extensively comprehend the role played by AhR in the cytokine/inflammation area.
ISSN: 1742-5255

inserm-00831662
http://www.hal.inserm.fr/inserm-00831662
DOI : 10.1517/17425255.2013.738194
PUBMED : 23230817

Éditeur(s) : HAL CCSD Public Library of Science
Résumé : International audience
BACKGROUND: We aimed to assess, for the first time, the nature of the indoor air contamination of hospitals. METHODS AND FINDINGS: More than 40 volatile organic compounds (VOCs) including aliphatic, aromatic and halogenated hydrocarbons, aldehydes, alcohols, ketones, ethers and terpenes were measured in a teaching hospital in France, from sampling in six sampling sites--reception hall, patient room, nursing care, post-anesthesia care unit, parasitology-mycology laboratory and flexible endoscope disinfection unit--in the morning and in the afternoon, during three consecutive days. Our results showed that the main compounds found in indoor air were alcohols (arithmetic means ± SD: 928±958 µg/m³ and 47.9±52.2 µg/m³ for ethanol and isopropanol, respectively), ethers (75.6±157 µg/m³ for ether) and ketones (22.6±20.6 µg/m³ for acetone). Concentrations levels of aromatic and halogenated hydrocarbons, ketones, aldehydes and limonene were widely variable between sampling sites, due to building age and type of products used according to health activities conducted in each site. A high temporal variability was observed in concentrations of alcohols, probably due to the intensive use of alcohol-based hand rubs in all sites. Qualitative analysis of air samples led to the identification of other compounds, including siloxanes (hexamethyldisiloxane, octamethyltrisiloxane, decamethylcyclopentasiloxane), anesthetic gases (sevoflurane, desflurane), aliphatic hydrocarbons (butane), esters (ethylacetate), terpenes (camphor, α-bisabolol), aldehydes (benzaldehyde) and organic acids (benzoic acid) depending on sites. CONCLUSION: For all compounds, concentrations measured were lower than concentrations known to be harmful in humans. However, results showed that indoor air of sampling locations contains a complex mixture of VOCs. Further multicenter studies are required to compare these results. A full understanding of the exposure of healthcare workers and patients to complex mixtures of chemical compounds can then be related to potential health outcomes.
ISSN: 1932-6203

hal-00874694
https://hal.archives-ouvertes.fr/hal-00874694
https://hal.archives-ouvertes.fr/hal-00874694/document
https://hal.archives-ouvertes.fr/hal-00874694/file/VOC_Contamination-accepted.pdf
DOI : 10.1371/journal.pone.0055535

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Exposure to environmental polycyclic aromatic hydrocarbons (PAHs), such as benzo(a) pyrene (B(a) P), has been linked to several health-threatening risks. PAHs were also shown to hinder adrenergic receptor (ADR) responses. As we previously demonstrated that Ba) P can directly interact with the beta 2ADR, we investigated here whether B(a) P could decrease beta 2ADR responsiveness by triggering receptor desensitization phenomena. We firstly showed that exposure to B(a) P reduced beta 2ADRmediated epinephrine-induced induction of NR4A gene mRNAs and of intracellular cAMP. Analysis of beta 2ADR protein expression demonstrated that B(a) P rapidly decreased membrane expression of beta 2ADR with a subsequent degradation of receptor protein. B(a) P exposure concomitantly rapidly increased the beta 2ADR mRNA levels. The use of the beta-blockers, propranolol and ICI 118.551, demonstrated the involvement of beta 2ADR itself in this increase. However, sustained exposure to Ba) P induced a diminution of beta 2ADR mRNA steady-state as a result of the acceleration of its degradation. Together, these results show that, beside the well-known activation of the aryl hydrocarbon receptor, PAH deleterious effects may involve the dysfunction of adrenergic responses through, in part, the desensitization of beta 2ADR. This may be taken in consideration when beta 2-agonists/antagonists are administered in patients exposed to important concentrations of PAHs, e.g. in cigarette smokers.
ISSN: 2045-2322

hal-01560151
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01560151
DOI : 10.1038/s41598-017-03646-4
PUBMED : 28607424

Éditeur(s) : HAL CCSD Nature Publishing Group
Résumé : International audience
Most tumors undergo metabolic reprogramming towards glycolysis, the so-called Warburg effect, to support growth and survival. Overexpression of IF1, the physiological inhibitor of the F0F1ATPase, has been related to this phenomenon and appears to be a relevant marker in cancer. Environmental contributions to cancer development are now widely accepted but little is known about the underlying intracellular mechanisms. Among the environmental pollutants humans are commonly exposed to, benzo[a]pyrene (B[a]P), the prototype molecule of polycyclic aromatic hydrocarbons (PAHs), is a well-known human carcinogen. Besides apoptotic signals, B[a]P can also induce survival signals in liver cells, both likely involved in cancer promotion. Our previous works showed that B[a]P elicited a Warburg-like effect, thus favoring cell survival. The present study aimed at further elucidating the molecular mechanisms involved in the B[a]P-induced metabolic reprogramming, by testing the possible involvement of IF1. We presently demonstrate, both in vitro and in vivo, that PAHs, especially B[a]P, strongly increase IF1 expression. Such an increase, which might rely on β2-adrenergic receptor activation, notably participates to the B[a]P-induced glycolytic shift and cell survival in liver cells. By identifying IF1 as a target of PAHs, this study provides new insights about how environmental factors may contribute to related carcinogenesis.
ISSN: 2045-2322

hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/document
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01518808/file/Hardonni%C3%A8re%20et%20al%202017.pdf
DOI : 10.1038/s41598-017-00269-7

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Predictive toxicology aims at developing methodologies to relate the results obtained from in vitro experiments to in vivo exposure. In the case of polycyclic aromatic hydrocarbons (PAHs), a substantial amount of knowledge on effects and modes of action has been recently obtained from in vitro studies of gene expression. In the current study, we built a physiologically based toxicokinetic (PBTK) model to relate in vivo and in vitro gene expression in case of exposure to benzo(a)pyrene (BaP), a referent PAH. This model was calibrated with two toxicokinetic datasets obtained on rats exposed either through intratracheal instillation or through intravenous administration and on an in vitro degradation study. A good agreement was obtained between the model's predictions and the concentrations measured in target organs, such as liver and lungs. Our model was able to relate correctly the gene expression for two genes targeted by PAHs, measured in vitro on primary human macrophages and in vivo in rat macrophages after exposure to BaP. Combining in vitro studies and PBTK modeling is promising for PAH risk assessment, especially for mixtures which are more efficiently studied in vitro than in vivo.
Toxicology Letters

hal-00873317
https://hal.archives-ouvertes.fr/hal-00873317
https://hal.archives-ouvertes.fr/hal-00873317/document
DOI : 10.1016/j.toxlet.2010.11.017
PUBMED : 21134426

Éditeur(s) : HAL CCSD Elsevier
Résumé : International audience
Lung diseases are aggravated by exposure to diesel exhaust particles (DEPs) found in air pollution. Macrophages are thought to play a crucial role in lung immune response to these pollutants, even if the mechanisms involved remain incompletely characterized. In the present study, we demonstrated that classically and alternative human macrophages (MΦ) exhibited increased secretion of PDGF-B in response to DEP extract (DEPe). This occurred via aryl hydrocarbon receptor (AhR)-activation because DEPe-induced PDGF-B overexpression was abrogated after AhR expression knock-down by RNA interference, in both M1 and M2 polarizing MΦ. In addition, TCDD and benzo(a)pyrene, two potent AhR ligands, also significantly increased mRNA expression of PDGF-B in M1 MΦ, whereas some weak ligands of AhR did not. We next evaluated the impact of conditioned media (CM) from MΦ culture exposed to DEPe or of recombinant PDGF-B onto lung fibroblast proliferation. The tyrosine kinase inhibitor, AG1295, prevents phosphorylations of PDGF-Rβ, AKT and ERK1/2 and the proliferation of MRC5 fibroblasts induced by recombinant PDGF-B and by CM from M1 polarizing MΦ, strongly suggesting that the PDGF-BB secreted by DEPe-exposed MΦ is sufficient to activate the PDGF-Rβ pathway of human lung fibroblasts. In conclusion, we demonstrated that human MΦ, whatever their polarization status, secrete PDGF-B in response to DEPe and that PDGF-B is a target gene of AhR. Therefore, induction of PDGF-B by DEP may participate in the deleterious effects towards human health triggered by such environmental urban contaminants.
ISSN: 0041-008X

hal-01146840
https://hal-univ-rennes1.archives-ouvertes.fr/hal-01146840
DOI : 10.1016/j.taap.2015.04.007
PUBMED : 25896968