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Saint-André-lez-Lille, France

Landsverk O.J.B.,University of Oslo | Barois N.,University of Oslo | Barois N.,Institute Pasteur Lille | Gregers T.F.,University of Oslo | And 2 more authors.
Immunology and Cell Biology

Mounting adaptive immune responses requires the cell surface expression of major histocompatibility class II molecules (MHC II) loaded with antigenic peptide. However, in the absence of antigenic stimuli, the surface population of MHC II is highly dynamic and exhibits a high turnover. Several studies have focused on the regulation of MHC II, and it is now recognized that ubiquitination is one key mechanism operating in the turnover of MHC II in B cells and dendritic cells. Here, we describe how the invariant chain (Ii) can prolong the half-life of MHC II through its action on the endocytic pathway. We find that in cells expressing intermediate-to-high levels of Ii, the half-life of MHC II is increased, with MHC II accumulating in slowly-maturing endosomes. The accumulation in endosomes is not due to retention of new MHC II directed from the endoplasmatic reticulum, as also mature, not Ii associated, MHC II is preserved. We suggest that this alternative endocytic pathway induced by Ii would serve to enhance the rate, quantity and diversity of MHC II antigen presentation by concentrating MHC II into specialized compartments and reducing the need for new MHC II synthesis upon antigen encounter. © 2011 Australasian Society for Immunology Inc. All rights reserved. Source

Sanders M.E.,Dairy and Food Culture Technologies | Heimbach J.T.,JHEIMBACH LLC | Pot B.,Institute Pasteur Lille | Tancredi D.,University of California at Davis | And 4 more authors.
Gut Microbes

The topic of "Health Claims Substantiation for Probiotic and Prebiotic Products" was discussed at the 8th annual International Scientific Association for Probiotics and Prebiotics (ISAPP) meeting. The topic is especially timely considering that the regulatory review process for health benefit claims on probiotic and prebiotic products in Europe has not resulted in a single claim being approved (120 negative opinions on probiotic claims and 19 negative opinions on prebiotic claims through February 2011). This situation in Europe and elsewhere has driven companies to seek clarity on a research path that would stand up to scientific scrutiny as well as satisfy regulatory demands for health claim substantiation. It can be challenging to negotiate rigid regulatory distinctions, such as between health and disease, when these states are more realistically represented by continua. One research approach focused on improved homeostasis is explored as a statistically robust approach to measuring physiological parameters in healthy populations, which are the required target for food and supplement claims. Diverse global regulatory frameworks complicate this issue, and harmonization of different approaches globally would simplify requirements for industry, decrease consumer confusion and improve the scientific framework for the research community to set up appropriate research pathways. This report highlights key points from this discussion. © 2011 Landes Bioscience. Source

Vennin C.,French Institute of Health and Medical Research | Vennin C.,Lille University of Science and Technology | Spruyt N.,French National Center for Scientific Research | Dahmani F.,French National Center for Scientific Research | And 10 more authors.

H19 is a long non-coding RNA precursor of miR-675microRNA. H19 is increasingly described to play key roles in the progression and metastasis of cancers from different tissue origins. We have previously shown that the H19 gene is activated by growth factors and increases breast cancer cell invasion. In this study, we established H19/miR-675 ectopic expression models of MDA-MB-231 breast cancer cells to further investigate the underlying mechanisms of H19 oncogenic action. We showed that overexpression of H19/miR-675 enhanced the aggressive phenotype of breast cancer cells including increased cell proliferation and migration in vitro, and increased tumor growth and metastasis in vivo. Moreover, we identified ubiquitin ligase E3 family (c-Cbl and Cbl-b) as direct targets of miR-675 in breast cancer cells. Using a luciferase assay, we demonstrated that H19, through its microRNA, decreased both c-Cbl and Cbl-b expression in all breast cancer cell lines tested. Thus, by directly binding c-Cbl and Cbl-b mRNA, miR-675 increased the stability and the activation of EGFR and c-Met, leading to sustained activation of Akt and Erk as well as enhanced cell proliferation and migration. Our data describe a novel mechanism of protumoral action of H19 in breast cancer. Source

Arnich N.,AFSSA | Canivenc-Lavier M.-C.,French National Institute for Agricultural Research | Kolf-Clauw M.,National Veterinary School of Toulouse | Coffigny H.,CEA Fontenay-aux-roses | And 9 more authors.
International Journal of Hygiene and Environmental Health

Since more than 10 years, risk assessment of bisphenol A (BPA) is debated at the international level. In 2008, the U.S. National Toxicology Program (NTP) expressed some concern for adverse effects, at current level of exposure to BPA, on developmental toxicity. In this context, the French Food Safety Agency (AFSSA) decided to review the toxicity data on BPA with a special focus on this endpoint at doses below 5. mg/kg bw/day (the no observed adverse effect level set by different regulatory bodies). This paper summarizes the conclusions of a collective assessment conducted by an expert Working Group from AFSSA. Studies were classified into 3 groups: (i) finding no toxicity, (ii) reporting results not considered to be of concern and (iii) indicating warning signals. The term " warning signal" means that no formal conclusion can be drawn regarding the establishment of a health based guidance value but the study raises some questions about the toxicity of BPA at low doses. It was concluded that studies are needed to ascertain the significance for human health of these warning signals and to be able to propose new methodologies for assessing the risks associated with low doses of BPA and more generally of endocrine disruptors. © 2011 Elsevier GmbH. Source

Poras H.,Pharmaleads | Duquesnoy S.,Pharmaleads | Dange E.,Pharmaleads | Pinon A.,Institute Pasteur Lille | And 3 more authors.
Journal of Biological Chemistry

Legionella pneumophila has been shown to secrete a protease termed major secretory protein (Msp). This protease belongs to the M4 family of metalloproteases and shares 62.9% sequence similarity with pseudolysin (EC With the aim of developing a specific enzymatic assay for the detection and quantification of Msp, the Fluofast substrate library was screened using both enzymes in parallel. Moreover, based on the crystal structure of pseudolysin, a model of the Msp structure was built. Screening of the peptide library identified a lead substrate specifically cleaved by Msp that was subsequently optimized by rational design. The proposed model for Msp is consistent with the enzymatic characteristics of the studied peptide substrates and provides new structural information useful for the characterization of the protease. This study leads to the identification of the first selective and high affinity substrate for Msp that is able to detect picomolar concentrations of the purified enzyme. The identified substrate could be useful for the development of a novel method for the rapid detection of Legionella. © 2012 by The American Society for Biochemistry and Molecular Biology, Inc. Source

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