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Gouin E.,Institute Pasteur Paris | Gouin E.,French Institute of Health and Medical Research | Gouin E.,French National Institute for Agricultural Research | Adib-Conquy M.,Institute Pasteur Paris | And 18 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2010

Listeria monocytogenes is an intracellular pathogen responsible for severe foodborne infections. It can replicate in both phagocytic and nonphagocytic mammalian cells. The infectious process at the cellular level has been studied extensively, but how the bacterium overcomes early host innate immune responses remains largely unknown. Here we show that InlC, a member of the internalin family, is secreted intracellularly and directly interacts with IKKα, a subunit of the IκB kinase complex critical for the phosphorylation of IκB and activation of NF-κB, the major regulator of innate immune responses. Infection experiments with WT Listeria or the inlC-deletion mutant and transfection of cells with InlC reveal that InlC expression impairs phosphorylation and consequently delays IκB degradation normally induced by TNF-α, a classical NF-κB stimulator. Moreover, infection of RAW 264.7 macrophages by the inlC mutant leads to increased production of proinflammatory cytokines compared with that obtained with the WT. Finally, in a peritonitis mouse model, we show that infection with the inlC mutant induces increased production of chemokines and increased recruitment of neutrophils in the peritoneal cavity compared with infection with WT. Together, these results demonstrate that InlC, by interacting with IKKα, dampens the host innate response induced by Listeria during the infection process. Source

Magid A.A.,CNRS Institute of Molecular Chemistry - Reims | Bobichon H.,University of Reims Champagne Ardenne | Borie N.,CNRS Institute of Molecular Chemistry - Reims | Lalun N.,Laboratoire Of Biologie Cellulaire | And 3 more authors.
Phytochemistry | Year: 2010

Phytochemical investigation of the MeOH extract of the stem bark of Antonia ovata led to the isolation of four triterpenoid saponins, along with eleven known compounds. Their structures were established by extensive 1D and 2D NMR, as well as HR-MS analysis and acid hydrolysis. All isolated saponins contained the same tetrasaccharide chain O-β-d-xylopyranosyl-(1 → 2)-O-β-d-glucopyranosyl-(1 → 3)-O-[β-d-glucopyranosyl-(1 → 2)]-β-d-glucuropyranoside linked to C-3 of esterified derivatives of R1-barrigenol, A1-barrigenol, barringtogenol C, or camelliagenin. Biological evaluation of the compounds against KB cell line revealed a potent cytotoxic activity with IC50 values ranging from 3.1 to 6.6 μM. The known compounds were found to be inactive at 10 μg/ml concentration. © 2009 Elsevier Ltd. All rights reserved. Source

Andre-Kerneis E.,Laboratoire dHematologie | Vincenot-Blouin A.,Laboratoire dHematologie | Fouillard L.,Service dHematologie Clinique | Abarah W.,Service dHematologie Clinique | And 4 more authors.
Hematologie | Year: 2013

We report here three cases of cup-like leukemia, a rare and underdiagnosed form of acute myeloblastic leukemia. Clinical and biological findings are relatively stereotypical : high blood cell counts, high frequency ofNPM1 and FLT3mutations and normal karyotype, and may resemble microgranular variant of acute promyelocytic leukemia because of frequent disseminated intravascular coagulation, mature phenotypic feature with low or absent expression of CD34 and HLADR and peculiar blastic morphology (proeminent nuclear invaginations). Therefore, recongnizing cup-like nuclear leukemia is important to avoid misdiagnosis of promyelocytic leukemia and should guide specific molecular analyses. Source

Llopis L.,Laboratoire Of Biologie Cellulaire | Boissel N.,University Paris Diderot | Dombret H.,University Paris Diderot
Hematologie | Year: 2011

Among the mutations found in acute myeloid leukemia (AML), those on genes IDH1 and IDH2 (for isocitrate dehydrogenase) are very frequent. According to the latest metaanalyses published, they would be present in approximately 7 % of AML and 14 % of de novo AML. The discovery of these mutations further expands our knowledge about this group of diseases, the mechanisms involved and the evaluation of the risk of relapse. The presence of an IDH1 mutation seems to be particularly poor prognosis among adults under 60 years who have the LAMCN/NPM1 + / FLT3wt phenotype and adults under 60 years. The impact of IDH2 mutation is not clear. However, these data could help to refine the 2008 WHO classification by adding new criteria for the evaluation of the benefit of the hematopietic stem cell allograft. This also brings the possibility of new therapeutic approaches. Source

Alabdul Magid A.,CNRS Institute of Molecular Chemistry - Reims | Lalun N.,Laboratoire Of Biologie Cellulaire | Long C.,Pierre Fabre | Borie N.,CNRS Institute of Molecular Chemistry - Reims | And 3 more authors.
Phytochemistry | Year: 2012

Six pentacyclic triterpenoid saponins, named antoniosides E-J along with two known alkaloids, were isolated from the leaves of Antonia ovata. Their structures were determined by the extensive use of 1D and 2D-NMR experiments along with HRESIMS analysis and acid hydrolysis. All isolated saponins contained the same pentasaccharide chain: 3-O-[β-d-glucopyranosyl-(1 → 2)]-[β-d-glucopyranosyl-(1 → 4)]-[β-d-glucopyranosyl-(1 → 3)-α-l-arabinopyranosyl(1 → 6)]-β-d-glucopyranoside, linked at C-3 of esterified derivatives of polyhydroxyoleanene triterpenoids (theasapogenol A and 15α-hydroxy-theasapogenol A). Isolated compounds were evaluated for their cytotoxic activity against KB cell line by a WST-1 assay, and the IC50 values ranged from 3.3 to 5.3 μM. © 2011 Elsevier Ltd. All rights reserved. Source

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