Search results for "SECRETION"

Temporal quantitative phosphoproteomics of ADP stimulation reveals novel central nodes in platelet activation and inhibition

2017

Adenosine diphosphate (ADP) enhances platelet activation by virtually any other stimulant to complete aggregation. It binds specifically to the G-protein-coupled membrane receptors P2Y1 and P2Y12, stimulating intracellular signaling cascades, leading to integrin aIIbb3 activation, a process antagonized by endothelial prostacyclin. P2Y12 inhibitors are among the most successful antiplatelet drugs, however, show remarkable variability in efficacy. We reasoned whether a more detailed molecular understanding of ADP-induced protein phosphorylation could identify (1) critical hubs in platelet signaling toward aggregation and (2) novel molecular targets for antiplatelet treatment strategies. We ap…

Effect of bone sialoprotein coated three-dimensional printed calcium phosphate scaffolds on primary human osteoblasts

2018

The combination of the two techniques of rapid prototyping 3D-plotting and bioactive surface functionalization is presented, with emphasis on the in vitro effect of Bone Sialoprotein (BSP) on primary human osteoblasts (hOBs). Our primary objective was to demonstrate the BSP influence on the expression of distinctive osteoblast markers in hOBs. Secondary objectives included examinations of the scaffolds' surface and the stability of BSP-coating as well as investigations of cell viability and proliferation. 3D-plotted calcium phosphate cement (CPC) scaffolds were coated with BSP via physisorption. hOBs were seeded on the coated scaffolds, followed by cell viability measurements, gene expressi…

2016

Orthopedic implant failure due to aseptic loosening and mechanical instability remains a major problem in total joint replacement. Improving osseointegration at the bone-implant interface may reduce micromotion and loosening. Bone sialoprotein (BSP) has been shown to enhance bone formation when coated onto titanium femoral implants and in rat calvarial defect models. However, the most appropriate method of BSP coating, the necessary level of BSP coating, and the effect of BSP coating on cell behavior remain largely unknown. In this study, BSP was covalently coupled to titanium surfaces via an aminosilane linker (APTES), and its properties were compared to BSP applied to titanium via physiso…

IL-17A/F in Leishmania major-resistant C57BL/6 mice.

2019

Proinflammatory IL-17 plays an important role in various diseases and defence against extracellular microorganisms. Healing of leishmaniasis is promoted by Th1/Tc1 cells, whereas Th2/Treg are associated with worsened disease outcome. In addition, high expression of IL-17A in Leishmania-susceptible BALB/c and artificial overexpression of IL-17A in T cells in resistant C57BL/6 mice worsened disease outcome. Since C57BL/6 mice lacking only IL-17A exhibited no phenotype, and IL-17A and IL-17F share similar receptors, but differentially regulate chemokine secretion, we studied mice lacking both IL-17A and IL-17F (IL-17A/F-/- ) in infections with Leishmania major. Interestingly, lesion volumes an…

Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model

2016

International audience; The metabolic syndrome (MetS) greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL) in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD). By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertrigl…

Impact of plant sterols enrichment dose on gut microbiota from lean and obese subjects using TIM-2 in vitro fermentation model

2019

There are scarce data on plant sterols (PS) and gut microbiota relationship. The purpose of this study is to compare the interaction between PS and gut microbiota through in vitro colonic fermentation studies using a validated system (TIM-2) with a PS-enriched dose (similar to 2 g/day) from two sources (food PS-source ingredient and commercial standard) using microbiota from lean and obese populations. Fecal sterols, short chain fatty acids (SCFA) and microbiota composition were determined by GC/MS, IEC, and 16S-sequencing, respectively.PS-feeding decreased coprostanol and ethylcoprostanol concentration and increased the production of acetate and butyrate (mainly with lean microbiota). In a…

Extracellular Vesicles Shed by Melanoma Cells Contain a Modified Form of H1.0 Linker Histone and H1.0 mRNA-binding Proteins

2016

Extracellular vesicles (EVs) are shed in the extracellular environment by both prokaryotes and eukaryotes. Although produced from both normal and cancer cells, malignant cells release a much higher amount of EVs, which also contain tumor-specific proteins and RNAs. We previously found that G26/24 oligodendroglioma cells shed EVs that contain the pro-apoptotic factors FasL and TRAIL1-2. Interestingly, G26/24 release, via EVs, extracellular matrix remodelling proteases3, and H1° histone protein4, and mRNA. To shed further light on the role of EVs in discarding proteins and mRNAs otherwise able to counteract proliferative signals, we studied a melanoma cell line (A375). We found that also thes…

The Secreted Protein C10orf118 Is a New Regulator of Hyaluronan Synthesis Involved in Tumour-Stroma Cross-Talk.

2021

Simple Summary Hyaluronan is a main glycosaminoglycan in extracellular matrix with an important role in breast cancer progression. Alterations in its synthesis and size may affect tu-mour growth and metastasis. Communication between stromal and breast cancer cells consists of the secretion of factors that provoke a series of cell signalling that influence cell fate and tis-sue microenvironment, by favouring tumour cell survival and motility. Here, we present the c10orf118 protein expressed in high amounts by breast tumour cells as a new regulator in hya-luronan synthesis. This protein is found both in Golgi and secreted in the extracellular matrix, whereas its role is still unknown. The sec…

Tissue Factor-Expressing Tumor-Derived Extracellular Vesicles Activate Quiescent Endothelial Cells via Protease-Activated Receptor-1

2017

Tissue factor (TF)-expressing tumor-derived extracellular vesicles (EVs) can promote metastasis and pre-metastatic niche formation, but the mechanisms by which this occurs remain largely unknown. We hypothesized that generation of activated factor X (FXa) by TF expressed on tumor-derived EV could activate protease-activated receptors (PARs) on non-activated endothelial cells to induce a pro-adhesive and pro-inflammatory phenotype. We obtained EV from TF-expressing breast (MDA-MB-231) and pancreatic (BxPC3 and Capan-1) tumor cell lines. We measured expression of E-selectin and secretion of interleukin-8 (IL-8) in human umbilical vein endothelial cells after exposure to EV and various immunol…

Red wine extract disrupts Th17 lymphocyte differentiation in a colorectal cancer context

2020

International audience; Scope: Scope: It is well established that immune response and inflammation promote tumoral progression. Immune cells communicate through direct contact or through cytokine secretion, and it is the pro-inflammatory status that will tip the balance toward tumor progression or anti-tumor immunity. It is demonstrated here that a red wine extract (RWE) can decrease inflammation through its action on the inflammasome complex. This study determines whether an RWE could impact other key actors of inflammation, including T helper 17 (Th17) immune cells in particular. Methods and results: Methods and results: Using an RWE containing 4.16 g of polyphenols/liter of wine, it is s…