scholarly journals Human Cytokine Response to ex vivo Amyloid-β Stimulation is Mediated by Genetic Factors

2005 ◽  
Vol 8 (2) ◽  
pp. 132-137 ◽  
Author(s):  
Danielle Posthuma ◽  
Ingrid Meulenbelt ◽  
Anton J.M. de Craen ◽  
Eco J.C. de Geus ◽  
P. Eline Slagboom ◽  
...  
Keyword(s):  
Genetic Factors ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Cytokine Response ◽  
Human Cytokine

scholarly journals Human Cytokine Response to ex vivo Amyloid-β Stimulation is Mediated by Genetic Factors

2005 ◽  
Vol 8 (2) ◽  
pp. 132-137 ◽  
Author(s):  
Danielle Posthuma ◽  
Ingrid Meulenbelt ◽  
Anton J. M. de Craen ◽  
Eco J. C. de Geus ◽  
P. Eline Slagboom ◽  
...  
Keyword(s):  
Neuronal Degeneration ◽  
Ex Vivo ◽  
Production Capacity ◽  
Amyloid Β ◽  
Cytokine Response ◽  
Tnf Alpha ◽  
Chronic Inflammatory Response ◽  
Alpha Production ◽  
Twin Families ◽  
Human Cytokine

AbstractThrough its ability to induce the enhanced release and production of cytokines, amyloid-β is responsible for the chronic inflammatory response that contributes to Alzheimer's disease (AD). Determining whether the response of monocytes to amyloid-β stimulation is under genetic control may help understand the basis of why some people are more prone to develop neuronal degeneration than others. In the current study we investigated the heritability of the cytokine (IL-10, IL-6, IL-1β, IL-1ra, TNF-[.alpha]) production capacity upon ex vivo stimulation with amyloid-β in whole blood samples of 222 twins and 85 singleton siblings from 139 extended twin families. It was found that individual differences in amyloid-β-induced cytokine production capacity are to a large extent of genetic origin, with heritability estimates ranging from 55% (IL-1β) to 68% (IL-6). We conclude that genes influencing amyloid-β-induced cytokine response may provide clues to the progression of AD pathology.

Phenolic Acids Exert Anticholinesterase and Cognition-Improving Effects

2018 ◽  
Vol 15 (6) ◽  
pp. 531-543 ◽  
Author(s):  
Dominik Szwajgier ◽  
Ewa Baranowska-Wojcik ◽  
Kamila Borowiec
Keyword(s):  
Phenolic Acids ◽  
Ex Vivo ◽  
Amyloid Β ◽  
Inhibitory Effect ◽  
In Vivo Studies ◽  
Amyloid Β Peptide ◽  
Beneficial Effects ◽  
Aβ Fibrils

Numerous authors have provided evidence regarding the beneficial effects of phenolic acids and their derivatives against Alzheimer's disease (AD). In this review, the role of phenolic acids as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) is discussed, including the structure-activity relationship. In addition, the inhibitory effect of phenolic acids on the formation of amyloid β-peptide (Aβ) fibrils is presented. We also cover the in vitro, ex vivo, and in vivo studies concerning the prevention and treatment of the cognitive enhancement.

scholarly journals Mouse Susceptibility to Anthrax Lethal Toxin Is Influenced by Genetic Factors in Addition to Those Controlling Macrophage Sensitivity

2004 ◽  
Vol 72 (8) ◽  
pp. 4439-4447 ◽  
Author(s):  
Mahtab Moayeri ◽  
Nathaniel W. Martinez ◽  
Jason Wiggins ◽  
Howard A. Young ◽  
Stephen H. Leppla
Keyword(s):  
Genetic Factors ◽  
Inbred Mouse ◽  
Inbred Strains ◽  
Lethal Toxin ◽  
Cytokine Response ◽  
Mouse Strains ◽  
Anthrax Lethal Toxin ◽  
Toll Like Receptor 4 ◽  
Oxide Synthase

ABSTRACT Bacillus anthracis lethal toxin (LT) produces symptoms of anthrax in mice and induces rapid lysis of macrophages (Mφ) derived from certain inbred strains. We used nine inbred strains and two inducible nitric oxide synthase (iNOS) knockout C57BL/6J strains polymorphic for the LT Mφ sensitivity Kif1C locus to analyze the role of Mφ sensitivity (to lysis) in LT-mediated cytokine responses and lethality. LT-mediated induction of cytokines KC, MCP-1/JE, MIP-2, eotaxin, and interleukin-1β occurred only in mice having LT-sensitive Mφ. However, while iNOS knockout C57BL/6J mice having LT-sensitive Mφ were much more susceptible to LT than the knockout mice with LT-resistant Mφ, a comparison of susceptibilities to LT in the larger set of inbred mouse strains showed a lack of correlation between Mφ sensitivity and animal susceptibility to toxin. For example, C3H/HeJ mice, harboring LT-sensitive Mφ and having the associated LT-mediated cytokine response, were more resistant than mice with LT-resistant Mφ and no cytokine burst. Toll-like receptor 4 (Tlr4)-deficient, lipopolysaccharide-nonresponsive mice were not more resistant to LT. We also found that CAST/Ei mice are uniquely sensitive to LT and may provide an economical bioassay for toxin-directed therapeutics. The data indicate that while the cytokine response to LT in mice requires Mφ lysis and while Mφ sensitivity in the C57BL/6J background is sufficient for BALB/cJ-like mortality of that strain, the contribution of Mφ sensitivity and cytokine response to animal susceptibility to LT differs among other inbred strains. Thus, LT-mediated lethality in mice is influenced by genetic factors in addition to those controlling Mφ lysis and cytokine response and is independent of Tlr4 function.

scholarly journals MHC-Independent Genetic Factors Control the Magnitude of CD4+ T Cell Responses to Amyloid-β Peptide in Mice through Regulatory T Cell-Mediated Inhibition

2011 ◽  
Vol 187 (9) ◽  
pp. 4492-4500 ◽  
Author(s):  
Cécile Toly-Ndour ◽  
Gabrielle Lui ◽  
Maria Manuel Nunes ◽  
Martine Bruley-Rosset ◽  
Pierre Aucouturier ◽  
...  
Keyword(s):  
T Cell ◽  
Regulatory T Cell ◽  
Genetic Factors ◽  
Amyloid Β ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Amyloid Β Peptide ◽  
Cell Responses

scholarly journals SPECT imaging of distribution and retention of a brain-penetrating bispecific amyloid-β antibody in a mouse model of Alzheimer’s disease

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Tobias Gustavsson ◽  
Stina Syvänen ◽  
Paul O’Callaghan ◽  
Dag Sehlin
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Ex Vivo ◽  
Photon Emission ◽  
Amyloid Β ◽  
Emission Computed Tomography ◽  
Brain Uptake ◽  
Brain Distribution ◽  
Model Of Alzheimer’S Disease ◽  
The Brain

Abstract Background Alzheimer’s disease (AD) immunotherapy with antibodies targeting amyloid-β (Aβ) has been extensively explored in clinical trials. The aim of this study was to study the long-term brain distribution of two radiolabeled monoclonal Aβ antibody variants – RmAb158, the recombinant murine version of BAN2401, which has recently demonstrated amyloid removal and reduced cognitive decline in AD patients, and the bispecific RmAb158-scFv8D3, which has been engineered for enhanced brain uptake via transferrin receptor-mediated transcytosis. Methods A single intravenous injection of iodine-125 (125I)-labeled RmAb158-scFv8D3 or RmAb158 was administered to AD transgenic mice (tg-ArcSwe). In vivo single-photon emission computed tomography was used to investigate brain retention and intrabrain distribution of the antibodies over a period of 4 weeks. Activity in blood and brain tissue was measured ex vivo and autoradiography was performed in combination with Aβ and CD31 immunostaining to investigate the intrabrain distribution of the antibodies and their interactions with Aβ. Results Despite faster blood clearance, [125I]RmAb158-scFv8D3 displayed higher brain exposure than [125I]RmAb158 throughout the study. The brain distribution of [125I]RmAb158-scFv8D3 was more uniform and coincided with parenchymal Aβ pathology, while [125I]RmAb158 displayed a more scattered distribution pattern and accumulated in central parts of the brain at later times. Ex vivo autoradiography indicated greater vascular escape and parenchymal Aβ interactions for [125I]RmAb158-scFv8D3, whereas [125I]RmAb158 displayed retention and Aβ interactions in lateral ventricles. Conclusions The high brain uptake and uniform intrabrain distribution of RmAb158-scFv8D3 highlight the benefits of receptor-mediated transcytosis for antibody-based brain imaging. Moreover, it suggests that the alternative transport route of the bispecific antibody contributes to improved efficacy of brain-directed immunotherapy.

Antibodies to β-Amyloid Decrease the Blood-to-Brain Transfer of β-Amyloid Peptide1

2002 ◽  
Vol 227 (8) ◽  
pp. 609-615 ◽  
Author(s):  
Weihong Pan ◽  
Beka Solomon ◽  
Lawrence M. Maness ◽  
Abba J. Kastin
Keyword(s):  
Ex Vivo ◽  
Amyloid Β ◽  
Brain Perfusion ◽  
Brain Parenchyma ◽  
Amyloid Angiopathy ◽  
Β Amyloid ◽  
Blocking Antibodies ◽  
The Brain

Amyloid-β peptides (Aβ) play an important role in the pathophysiology of dementia of the Alzheimer's type and in amyloid angiopathy. Aβ outside the CNS could contribute to plaque formation in the brain where its entry would involve interactions with the blood-brain barrier (BBB). Effective antibodies to Aβ have been developed in an effort to vaccinate against Alzheimer's disease. These antibodies could interact with Aβ in the peripheral blood, block the passage of Aβ across the BBB, or prevent Aβ deposition within the CNS. To determine whether the blocking antibodies act at the BBB level, we examined the influx of radiolabeled Aβ (125I-Aβ1-40) into the brain after ex-vivo incubation with the antibodies. Antibody mAb3D6 (élan Company) reduced the blood-to-brain influx of Aβ after iv bolus injection. It also significantly decreased the accumulation of Aβ in brain parenchyma. To confirm the in-vivo study and examine the specificity of mAb3D6, in-situ brain perfusion in serum-free buffer was performed after incubation of 125I-Aβ1-40 with another antibody mAbmc1 (DAKO Company). The presence of mAbmc1 also caused significant reduction of the influx of Aβ into the brain after perfusion. Therefore, effective antibodies to Aβ can reduce the influx of Aβ1-40 into the brain.

scholarly journals Development and Optimization of a Fluorescent Imaging System to Detect Amyloid-β Proteins: Phantom Study

2018 ◽  
Vol 9 ◽  
pp. 117959721878108 ◽  
Author(s):  
David Tes ◽  
Karl Kratkiewicz ◽  
Ahmed Aber ◽  
Luke Horton ◽  
Mohsin Zafar ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Imaging System ◽  
Ex Vivo ◽  
Amyloid Β ◽  
The United States ◽  
Fluorescent Imaging ◽  
Fluorescent Properties ◽  
In Vivo Experiments ◽  
The Brain

Alzheimer disease is the most common form of dementia, affecting more than 5 million people in the United States. During the progression of Alzheimer disease, a particular protein begins to accumulate in the brain and also in extensions of the brain, ie, the retina. This protein, amyloid-β (Aβ), exhibits fluorescent properties. The purpose of this research article is to explore the implications of designing a fluorescent imaging system able to detect Aβ proteins in the retina. We designed and implemented a fluorescent imaging system with a range of applications that can be reconfigured on a fluorophore to fluorophore basis and tested its feasibility and capabilities using Cy5 and CRANAD-2 imaging probes. The results indicate a promising potential for the imaging system to be used to study the Aβ biomarker. A performance evaluation involving ex vivo and in vivo experiments is planned for future study.

scholarly journals Rupintrivir reduces RV-induced TH-2 cytokine IL-4 in precision-cut lung slices (PCLS) of HDM-sensitized mice ex vivo

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Olga Danov ◽  
Lisa Lasswitz ◽  
Helena Obernolte ◽  
Christina Hesse ◽  
Armin Braun ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Antiviral Drug ◽  
Cytokine Response ◽  
Experimental Conditions ◽  
Tnf Α ◽  
Dust Mite ◽  
Ifn Γ ◽  
Inflammatory Immune Response ◽  
Precision Cut Lung Slices

Abstract Background Antiviral drugs such as rupintrivir may have an immune-modulatory effect in experimentally induced allergic asthma with subsequent RV infection. We infected lung slices of house-dust mite (HDM)-sensitized asthmatic mice ex vivo with human rhinovirus (RV) and investigated the effect of the antiviral drug rupintrivir on RV-induced cytokine response in lung tissue of HDM-sensitized mice ex vivo. Methods Mice were sensitized with HDM. Precision-cut lung slices (PCLS) were prepared from HDM-sensitized or non-sensitized mice. Lung slices were infected ex vivo with RV or RV together with rupintrivir. Modulation of immune responses was evaluated by cytokine secretion 48 h post infection. Results In vivo HDM sensitization resulted in a TH-2/TH-17-dominated cytokine response that persisted in PCLS ex vivo. RV infection of PCLS from non-sensitized mice resulted in the induction of an antiviral and pro-inflammatory immune response, as indicated by the secretion of IFN-α, IFN-β, IFN-γ, TNF-α, MCP-1, IP-10, IL-10, and IL-17A. In contrast, PCLS from HDM-sensitized mice showed an attenuated antiviral response, but exaggerated IL-4, IL-6, and IL-10 secretion upon infection. Rupintrivir inhibited exaggerated pro-inflammatory cytokine IL-6 and TH-2 cytokine IL-4 in HDM-sensitized mice. Conclusions In summary, this study demonstrates that treatment with rupintrivir influences virus-induced IL-4 and IL-6 cytokine release under experimental conditions ex vivo.

scholarly journals Exposure of Cord Blood to Mycobacterium bovis BCG Induces an Innate Response but Not a T-Cell Cytokine Response

2008 ◽  
Vol 15 (11) ◽  
pp. 1666-1673 ◽  
Author(s):  
M. L. V. Watkins ◽  
P. L. Semple ◽  
B. Abel ◽  
W. A. Hanekom ◽  
G. Kaplan ◽  
...  
Keyword(s):  
Cord Blood ◽  
Mycobacterium Bovis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Nk Cell ◽  
Ex Vivo ◽  
Cytokine Response ◽  
Healthy Human ◽  
Blood Samples ◽  
Ifn Γ

ABSTRACT Despite routine vaccination with Mycobacterium bovis bacillus Calmette-Guérin (BCG) soon after birth, tuberculosis in babies and adults remains epidemic in South Africa. The immune responses of the naïve newborn child and how they are affected by vaccination with BCG are as yet not fully understood. Immunity during pregnancy and in healthy human newborns may be skewed toward type 2 cytokine production; however, it is type 1 cytokines that are required for protection against M. tuberculosis infection. To better understand neonatal cytokine responses prior to and following exposure to mycobacteria, we have collected cord blood and peripheral blood samples and evaluated the cytokine response following ex vivo incubation with BCG. Gamma interferon (IFN-γ), interleukin 10 (IL-10), IL-12, and low levels of IL-13 and IL-5 but no IL-4 were secreted into the culture supernatant of cord blood mononuclear cells. Intracellular staining showed that IL-10 and IL-12 were produced by monocytes and that IFN-γ was produced by natural killer (NK) cells but not by CD4+ or CD8+ T cells. In contrast, in the peripheral blood samples collected from babies 13 weeks post-BCG vaccination, IFN-γ was detected within CD4+ and CD8+ cells. Taken together, the data suggest a central role for Th1 cytokines in naïve as well as BCG-vaccinated neonates in the protective immune response to tuberculosis. NK cell-derived IFN-γ produced in naïve neonates likely plays a key protective role via monocyte activation and the priming of a subsequent adaptive Th1 response.

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