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131.
In vivo adjuvant-induced mobilization and maturation of gut dendritic cells after oral administration of cholera toxin 总被引:4,自引:0,他引:4
Anjuère F Luci C Lebens M Rousseau D Hervouet C Milon G Holmgren J Ardavin C Czerkinsky C 《Journal of immunology (Baltimore, Md. : 1950)》2004,173(8):5103-5111
Although dendritic cells (DCs) regulate immune responses, they exhibit functional heterogeneity depending on their anatomical location. We examined the functional properties of intestinal DCs after oral administration of cholera toxin (CT), the most potent mucosal adjuvant. Two CD11c+ DC subsets were identified both in Peyer's patches and mesenteric lymph nodes (MLN) based on the expression of CD8alpha (CD8+ and CD8- DCs, respectively). A third subset of CD11c+CD8int was found exclusively in MLN. Feeding mice with CT induced a rapid and transient mobilization of a new CD11c+CD8- DC subset near the intestinal epithelium. This recruitment was associated with an increased production of the chemokine CCL20 in the small intestine and was followed by a massive accumulation of CD8int DCs in MLN. MLN DCs from CT-treated mice were more potent activators of naive T cells than DCs from control mice and induced a Th2 response. This increase in immunostimulating properties was accounted for by CD8int and CD8- DCs, whereas CD8+ DCs remained insensitive to CT treatment. Consistently, the CD8int and CD8- subsets expressed higher levels of costimulatory molecules than CD8+ and corresponding control DCs. Adoptive transfer experiments showed that these two DC subsets, unlike CD8+ DCs, were able to present Ags orally coadministered with CT in an immunostimulating manner. The ability of CT to mobilize immature DCs in the intestinal epithelium and to promote their emigration and differentiation in draining lymph nodes may explain the exceptional adjuvant properties of this toxin on mucosal immune responses. 相似文献
132.
Bach S Tribouillard D Talarek N Desban N Gug F Galons H Blondel M 《Methods (San Diego, Calif.)》2006,39(1):72-77
Recently, we have developed a yeast-based (Saccharomyces cerevisiae) assay to isolate drugs active against mammalian prions. The initial assumption was that mechanisms controlling prion appearance and/or propagation could be conserved from yeast to human, as it is the case for most of the major cell biology regulatory mechanisms. Indeed, the vast majority of drugs we isolated as active against both [PSI(+)] and [URE3] budding yeast prions turned out to be also active against mammalian prion in three different mammalian cell-based assays. These results strongly argue in favor of common prion controlling mechanisms conserved in eukaryotes, thus validating our yeast-based assay and also the use of budding yeast to identify antiprion compounds and to study the prion world. 相似文献
133.
This protocol allows the accurate quantification of cell-penetrating peptide (CPP) cellular uptake by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). Quantification is based on the use of an internal standard with same chemical structure as the analyte but labeled with a stable isotope. The analyte and the standard can both be obtained by standard solid-phase peptide synthesis using commercially available amino acids. They are functionalized by biotin to allow their easy purification before MALDI-TOF MS analysis. The method allows determination of the amount of intact internalized peptide and the identification of potential intracellular digests. It can be used to simultaneously compare the uptake of several peptides, and can also be applied to the quantification of peptidic cargoes and the study of their intracellular stability. It is therefore a potent tool to study the mechanisms of CPPs internalization and to select new carriers for drug delivery. This protocol will take approximately 5 hours for the analysis of 12 samples (not including the time for cell incubation with peptides). 相似文献
134.
Tribouillard D Bach S Gug F Desban N Beringue V Andrieu T Dormont D Galons H Laude H Vilette D Blondel M 《Biotechnology journal》2006,1(1):58-67
Prions are misfolded proteins capable of propagating their altered conformation which are commonly considered as the causative agent of transmissible spongiform encephalopathies, a class of fatal neurodegenerative diseases. Currently, no treatment for prion-based diseases is available. Recently we have developed a rapid, yeast-based, two-step assay to screen for anti-prion drugs [1]. This new method allowed us to identify several compounds that are effective in vivo against budding yeast [PSI+] and [URE3] prions but also able to promote mammalian prion clearance in three different cell culture-based assays. Taken together, these results validate our method as an economic and efficient high-throughput screening approach to identify novel prion inhibitors or to carry on comprehensive structure-activity studies for already isolated anti-mammalian prion drugs. These results suggest furthermore that biochemical pathways controlling prion formation and/or maintenance are conserved from yeast to human and thus amenable to pharmacological and genetic analysis. Finally, it would be very interesting to test active drugs isolated using the yeast-based assay in models for other diseases (neurodegenerative or not) involving amyloid fibers like Huntington's, Parkinson's or Alzheimer's diseases. 相似文献
135.
Woldeamanuel Birru Ross T. Fernley Lloyd D. Graham Julian Grusovin Ronald J. Hill Albert Hofmann Linda Howell Peter J. James Karen E. Jarvis Wynona M. Johnson Dionne A. Jones Christa Leitner Andris J. Liepa George O. Lovrecz Louis Lu Roland H. Nearn Brian J. O’Driscoll Tram Phan Matthew Pollard Kathleen A. Turner David A. Winkler 《Bioorganic & medicinal chemistry》2010,18(15):5647-5660
Nuclear hormone receptors, such as the ecdysone receptor, often display a large amount of induced fit to ligands. The size and shape of the binding pocket in the EcR subunit changes markedly on ligand binding, making modelling methods such as docking extremely challenging. It is, however, possible to generate excellent 3D QSAR models for a given type of ligand, suggesting that the receptor adopts a relatively restricted number of binding site configurations or ‘attractors’. We describe the synthesis, in vitro binding and selected in vivo toxicity data for γ-methylene γ-lactams, a new class of high-affinity ligands for ecdysone receptors from Bovicola ovis (Phthiraptera) and Lucilia cuprina (Diptera). The results of a 3D QSAR study of the binding of methylene lactams to recombinant ecdysone receptor protein suggest that this class of ligands is indeed recognised by a single conformation of the EcR binding pocket. 相似文献
136.
Fabienne Le Grand Xavier de Montaudouin Yanic Marty 《Journal of invertebrate pathology》2010,104(2):110-118
The present report presents the first evidence of disseminated neoplasia (DN) in cockles Cerastoderma edule from Arcachon Bay (France). Aneuploidy of neoplastic cells allowed the use of flow cytometry (FCM) to diagnose and stage DN. A 1 year survey (2007) of the prevalence and intensity (% of aneuploid circulating cells in neoplastic cockles) was conducted. Prevalences ranged from 2.2% (June) to 13.6% (May), and disease intensity ranged from 18.7% (June) to 95.5% (September). These percentages were not correlated with seawater temperature, but rather showed unexplained oscillations over the year. Prevalence and intensity of DN were higher in cockles found at the surface of sediment compared to those buried normally (11.8% vs. 6.7% and 53.0% vs. 40.6%, respectively, p < 0.05). DN could thus be one mechanism leading to unexplained presence of cockles at the surface of the sediment in Arcachon Bay. Ploidy characteristics of neoplastic cells were also investigated using FCM, revealing an unusual, broad continuum of ploidy distribution from 1.6 to 9.6n. Ploidy values were not in whole numbers in contrast to the rounded values reported in other studies. Ploidy varied according to DN intensity, with the ploidy distribution of neoplastic cells from lightly-diseased cockles being unimodal (3.7n median). In contrast, highly-diseased cockles showed a bimodal ploidy distribution (3.0n and 4.7n medians). This suggests that, in cockles from Arcachon Bay, mechanisms leading to aneuploidy are complex, developing during disease progression. 相似文献
137.
Human CD4+CD25+ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas/Fas ligand-dependent mechanism 总被引:7,自引:0,他引:7
Venet F Pachot A Debard AL Bohe J Bienvenu J Lepape A Powell WS Monneret G 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(9):6540-6547
Although it is known that septic shock induces immunosuppression, the mechanism for this phenomenon is not well understood. Monocytes play a central role in septic shock pathophysiology, which is also characterized by an increased proportion of natural regulatory T (Treg) cells. We therefore investigated whether Treg could be involved in the decreased monocyte expression of CD14 and HLA-DR observed during septic shock. We demonstrated that human Treg inhibit LPS-induced retention of monocyte CD14. Because loss of CD14 is a hallmark of monocyte apoptosis, this suggests that Treg inhibit monocyte survival. This effect was largely mediated through the release of a soluble mediator that was not identical with either IL-10 or IL-4. The Fas/FasL pathway participated in the effect as it was blocked by anti-FasL Abs and reproduced by Fas agonist and recombinant soluble FasL. Furthermore, expression of FasL was much higher on Treg than on their CD25(-) counterparts. Collectively, these results indicate that Treg act on monocytes by inhibiting their LPS-induced survival through a proapoptotic mechanism involving the Fas/FasL pathway. This may be an important mechanism for septic shock-induced immunosuppression and may offer new perspectives for the treatment of this deadly disease. 相似文献
138.
Fabienne Meier-Abt Younes Mokrab Kenji Mizuguchi 《The Journal of membrane biology》2006,208(3):213-227
Organic anion-transporting polypeptides (human, OATPs; other animals, Oatps; gene symbol, SLCO/Slco) form a transport protein superfamily that mediates the translocation of amphipathic substrates across the plasma membrane
of animal cells. So far, OATPs/Oatps have been identified in human, rat and mouse tissues. In this study, we used bioinformatic
tools to detect new members of the OATP/SLCO superfamily in nonmammalian species and to build models for the three-dimensional structure of OATPs/Oatps. New OATP/SLCO superfamily members, some of which form distinct novel families, were identified in chicken, zebrafish, frog, fruit fly and
worm species. The lack of OATP/SLCO superfamily members in plants, yeast and bacteria suggests the emergence of an ancient Oatp protein in an early ancestor
of the animal kingdom. Structural models were generated for the representative members OATP1B3 and OATP2B1 based on the known
structures of the major facilitator superfamily of transport proteins. A model was also built for the large extracellular
region between transmembrane helices 9 and 10, following the identification of a novel homology with the Kazal-type serine
protease inhibitors. Along with the electrostatic potential and the conservation of key amino acid residues, we propose a
common transport mechanism for all OATPs/Oatps, whereby substrates are translocated through a central, positively charged
pore in a rocker-switch type of mechanism. Several amino acid residues were identified that may play crucial roles in the
proposed transport mechanism.
Electronic Supplementary Material Electronic Supplementary material is available for this article at
and accessible for authorised users. 相似文献
139.
Sagan S Burlina F Delaroche D Aussedat B Aubry S Bolbach G Lavielle S Chassaing G 《Journal de la Société de Biologie》2006,200(3):213-219
Trojan peptides or cell-penetrating peptides (CPP) are natural or designed peptides identified as cellular membrane-crossing molecules, in particular through their potency to vehiculate various kinds of compounds to the cytoplasm and nucleus of living cells. The indirect methods used so far to detect these peptides in cells led to controversial hypotheses on the mechanism of their cell entry. Therefore, we have developed a MALDI-TOF mass spectrometry-based quantification method to track these peptides inside cells. This new method is presented in this review. 相似文献
140.