Search results for "activation"
showing 10 items of 2079 documents
Multi-criteria framework as an innovative tradeoff approach to determine the shelf-life of high pressure-treated poultry
2016
International audience; A multi-criteria framework combining safety, hygiene and sensorial quality was developed to investigate the possibility of extending the shelf-life and/or removing lactate by applying High Hydrostatic Pressure (HHP) in a ready-to-cook (RTC) poultry product. For this purpose, Salmonella and Listeria monocytogenes were considered as safety indicators and Escherichia coli as hygienic indicator. Predictive modeling was used to determine the influence of HHP and lactate concentration on microbial growth and survival of these indicators. To that end, probabilistic assessment exposure models developed in a previous study (Lerasle, M., Guillou, S., Simonin, H., Anthoine, V.,…
Can Immunogenic Chemotherapies Relieve Cancer Cell Resistance to Immune Checkpoint Inhibitors?
2019
The unprecedented clinical activity of checkpoint blockade in several types of cancers has formally demonstrated that anti-tumor immune responses are crucial in cancer therapy. Durable responses seen in patients treated with immune checkpoint inhibitors (ICI) show that they can trigger the establishment of long-lasting immunologic memory. This beneficial outcome is however achieved for a limited number of patients. In addition, late relapses are emerging suggesting the development of acquired resistances that compromise the anticancer efficacy of ICI. How can this be prevented through combination therapies? We here review the functions of immune checkpoints, the successes of ICI in treating…
Propeptide glycosylation and galectin‐3 binding decrease proteolytic activation of human proMMP‐9/progelatinase B
2019
Matrix metalloproteinases (MMPs) are secreted as proenzymes, containing propeptides that interact with the catalytic zinc, thereby controlling MMP activation. The MMP‐9 propeptide is unique in the MMP family because of its post‐translational modification with an N‐linked oligosaccharide. ProMMP‐9 activation by MMP‐3 occurs stepwise by cleavage of the propeptide in an aminoterminal (pro‐AT) and carboxyterminal (pro‐CT) peptide. We chemically synthesized aglycosyl pro‐AT and pro‐CT and purified recombinant glycosylated pro‐ATS f−9. First, we report new cleavage sites in the MMP‐9 propeptide by MMP‐3 and neutrophil elastase. Additionally, we demonstrated with the use of western blot analysis a…
Intracellular fluoride influences TASK mediated currents in human T cells.
2019
The expression of Kv1.3 and KCa channels in human T cells is essential for maintaining cell activation, proliferation and migration during an inflammatory response. Recently, an additional residual current, sensitive to anandamide and A293, compounds specifically inhibiting currents mediated by TASK channels, was observed after complete pharmacological blockade of Kv1.3 and KCa channels. This finding was not consistently observed throughout different studies and, an in-depth review of the different recording conditions used for the electrophysiological analysis of K+ currents in T cells revealed fluoride as major anionic component of the pipette intracellular solutions in the initial studie…
In Situ Activation of Pituitary-Infiltrating T Lymphocytes in Autoimmune Hypophysitis
2017
AbstractAutoimmune hypophysitis (AH) is a chronic inflammatory disease characterized by infiltration of T and B lymphocytes in the pituitary gland. The mechanisms through which infiltrating lymphocytes cause disease remain unknown. Using a mouse model of AH we assessed whether T lymphocytes undergo activation in the pituitary gland. Infiltrating T cells co-localized with dendritic cells in the pituitary and produced increased levels of interferon-γ and interleukin-17 upon stimulation in vitro. Assessing proliferation of CD3- and B220-postive lymphocytes by double immunohistochemistry (PCNA-staining) and flow cytometry (BrdU incorporation) revealed that a discrete proportion of infiltrating …
Targeting vascular (endothelial) dysfunction
2016
Abstract Cardiovascular diseases are major contributors to global deaths and disability-adjusted life years, with hypertension a significant risk factor for all causes of death. The endothelium that lines the inner wall of the vasculature regulates essential haemostatic functions, such as vascular tone, circulation of blood cells, inflammation and platelet activity. Endothelial dysfunction is an early predictor of atherosclerosis and future cardiovascular events. We review the prognostic value of obtaining measurements of endothelial function, the clinical techniques for its determination, the mechanisms leading to endothelial dysfunction and the therapeutic treatment of endothelial dysfunc…
Contribution of the commensal microbiota to atherosclerosis and arterial thrombosis
2018
The commensal gut microbiota is an environmental factor that has been implicated in the development of cardiovascular disease. The development of atherosclerotic lesions is largely influenced not only by the microbial-associated molecular patterns of the gut microbiota but also by the meta-organismal trimethylamine N-oxide pathway. Recent studies have described a role for the gut microbiota in platelet activation and arterial thrombosis. This review summarizes the results from gnotobiotic mouse models and clinical data that linked microbiota-induced pattern recognition receptor signalling with atherogenesis. Based on recent insights, we here provide an overview of how the gut microbiota cou…
Glucagon-like peptide-1 receptor signalling reduces microvascular thrombosis, nitro-oxidative stress and platelet activation in endotoxaemic mice
2016
Background and purpose Excessive inflammation in sepsis causes microvascular thrombosis and thrombocytopenia associated with organ dysfunction and high mortality. The present studies aimed to investigate whether inhibition of dipeptidyl peptidase-4 (DPP-4) and supplementation with glucagon-like peptide-1 (GLP-1) receptor agonists improved endotoxaemia-associated microvascular thrombosis via immunomodulatory effects. Experimental approach Endotoxaemia was induced in C57BL/6J mice by a single injection of LPS (17.5 mg kg-1 for survival and 10 mg kg-1 for all other studies). For survival studies, treatment was started 6 h after LPS injection. For all other studies, drugs were injected 48 h bef…
Eomes broadens the scope of CD8 T-cell memory by inhibiting apoptosis in cells of low affinity.
2020
The memory CD8 T-cell pool must select for clones that bind immunodominant epitopes with high affinity to efficiently counter reinfection. At the same time, it must retain a level of clonal diversity to allow recognition of pathogens with mutated epitopes. How the level of diversity within the memory pool is controlled is unclear, especially in the context of a selective drive for antigen affinity. We find that preservation of clones that bind the activating antigen with low affinity depends on expression of the transcription factor Eomes in the first days after antigen encounter. Eomes is induced at low activating signal strength and directly drives transcription of the prosurvival protein…
Activin Receptor Ligand Blocking and Cancer Have Distinct Effects on Protein and Redox Homeostasis in Skeletal Muscle and Liver
2019
Muscle wasting in cancer cachexia can be alleviated by blocking activin receptor type 2 (ACVR2) ligands through changes in protein synthesis/degradation. These changes in cellular and protein metabolism may alter protein homeostasis. First, we elucidated the acute (1–2 days) and 2-week effects of blocking ACVR2 ligands by soluble activin receptor 2B (sACVR2B-Fc) on unfolded protein response (UPR), heat shock proteins (HSPs) and redox balance in a healthy mouse skeletal muscle. Second, we examined UPR, autophagy and redox balance with or without sACVR2B-Fc administration in muscle and liver of C26 tumor-bearing mice. The indicators of UPR and HSPs were not altered 1–2 days after a single sAC…