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.

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

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 FOXP3 expression accurately defines the population of intratumoral regulatory T cells that selectively accumulate in metastatic melanoma lesions

Blood ◽  
2008 ◽  
Vol 112 (13) ◽  
pp. 4953-4960 ◽  
Author(s):  
Mojgan Ahmadzadeh ◽  
Aloisio Felipe-Silva ◽  
Bianca Heemskerk ◽  
Daniel J. Powell ◽  
John R. Wunderlich ◽  
...  
Keyword(s):  
T Cells ◽  
Tumor Microenvironment ◽  
Metastatic Melanoma ◽  
Treg Cell ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Production Capacity ◽  
Biological Marker ◽  
Foxp3 Expression ◽  
Treg Cells

Abstract Regulatory T (Treg) cells are often found in human tumors; however, their functional characteristics have been difficult to evaluate due to low cell numbers and the inability to adequately distinguish between activated and Treg cell populations. Using a novel approach, we examined the intracellular cytokine production capacity of tumor-infiltrating T cells in the single-cell suspensions of enzymatically digested tumors to differentiate Treg cells from effector T cells. Similar to Treg cells in the peripheral blood of healthy individuals, tumor-infiltrating FOXP3+CD4 T cells, unlike FOXP3− T cells, were unable to produce IL-2 and IFN-γ upon ex vivo stimulation, indicating that FOXP3 expression is a valid biological marker for human Treg cells even in the tumor microenvironment. Accordingly, we enumerated FOXP3+CD4 Treg cells in intratumoral and peritumoral sections of metastatic melanoma tumors and found a significant increase in proportion of FOXP3+CD4 Treg cells in the intratumoral compared with peritumoral areas. Moreover, their frequencies were 3- to 5-fold higher in tumors than in peripheral blood from the same patients or healthy donors, respectively. These findings demonstrate that the tumor-infiltrating CD4 Treg cell population is accurately depicted by FOXP3 expression, they selectively accumulate in tumors, and their frequency in peripheral blood does not properly reflect tumor microenvironment.

TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls

2015 ◽  
Vol 44 (6) ◽  
pp. 590-601 ◽  
Author(s):  
Mehrdad Farrokhi ◽  
Masoud Etemadifar ◽  
Maryam Sadat Jafary Alavi ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Mohaddeseh Behjati ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Peripheral Blood ◽  
Tnf Alpha ◽  
Healthy Controls ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Alpha Production ◽  
Multiple Sclerosis Patients

Modulation by dexamethasone of phospholipase A2 activities in endotoxemic guinea pigs

1995 ◽  
Vol 79 (4) ◽  
pp. 1271-1277 ◽  
Author(s):  
C. M. De Castro ◽  
M. F. Bureau ◽  
M. A. Nahori ◽  
C. H. Dumarey ◽  
B. B. Vargaftig ◽  
...  
Keyword(s):  
Bronchoalveolar Lavage ◽  
Phospholipase A2 ◽  
Alveolar Macrophages ◽  
Guinea Pigs ◽  
Ex Vivo ◽  
Neutrophil Infiltration ◽  
Tnf Alpha ◽  
Necrosis Factor Alpha ◽  
Intracellular Enzyme ◽  
Lps Challenge

One hour after lipopolysaccharide (LPS) administration (intravenous) in guinea pigs, alveolar macrophages are primed for an ex vivo increased secretion of arachidonic acid metabolites from the cyclooxygenase and the lipoxygenase pathways, with challenge by a second stimulus. At the same time, maximal levels of tumor necrosis factor-alpha (TNF-alpha) are observed in the circulation and in the bronchoalveolar lavage fluid. An extracellular form of phospholipase A2, corresponding probably to the low-molecular-mass type II enzyme, known to accumulate in inflammatory exudates, appears later in the serum of guinea pigs, to reach maximal levels 6 h after the LPS. Unlike the intracellular enzyme, extracellular phospholipase A2 is not increased by LPS in alveolar macrophages or in bronchoalveolar lavage fluids. After 24 h, at the time when neither TNF-alpha nor extracellular phospholipase A2 is present and priming of macrophages is over, maximal neutrophil infiltration is observed in the alveolar space of LPS-treated guinea pigs. Dexamethasone administered repeatedly during 3 days (subcutaneous) before the LPS challenge prevented both early events such as the macrophage priming and the TNF-alpha appearance and later events such as extracellular phospholipase A2 release and neutrophil recruitment.

scholarly journals Decreased whole blood TNFα production capacity after acute alcohol exposure and LPS stimulation ex vivo

Critical Care ◽  
2010 ◽  
Vol 14 (Suppl 1) ◽  
pp. P13 ◽  
Author(s):  
A Gavala ◽  
K Venetsanou ◽  
C Kittas ◽  
E Manolis ◽  
A Yiambides ◽  
...  
Keyword(s):  
Whole Blood ◽  
Ex Vivo ◽  
Production Capacity ◽  
Alcohol Exposure

scholarly journals Mitochondrial Dysfunction Induces Epigenetic Dysregulation by H3K27 Hyperacetylation to Perturb Active Enhancers in Parkinson’s Disease Models

2019 ◽  
Author(s):  
Minhong Huang ◽  
Dan Lou ◽  
Adhithiya Charli ◽  
Dehui Kong ◽  
Huajun Jin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Neuronal Degeneration ◽  
Ex Vivo ◽  
Genetic Mutation ◽  
Common Mechanism ◽  
Enhancer Activity ◽  
Active Enhancer ◽  
Environmental Component

AbstractGenetic mutations explain only 10-15% of cases of Parkinson’s disease (PD), while an overriding environmental component has been implicated in the etiopathogenesis of PD. But regardless of where the underlying triggers for the onset of familial and sporadic PD fall on the gene-environment axis, mitochondrial dysfunction emerges as a common mediator of dopaminergic neuronal degeneration. Herein, we employ a multidisciplinary approach to convincingly demonstrate that neurotoxicant exposure- and genetic mutation-driven mitochondrial dysfunction share a common mechanism of epigenetic dysregulation. Under both scenarios, lysine 27 acetylation of likely variant H3.2 (H3.2K27ac) increased in dopaminergic neuronal models of PD, thereby opening that region to active enhancer activity via H3K27 hyperacetylation. These vulnerable epigenomic loci represent potential transcription factor motifs for PD pathogenesis. We further confirmed the mitochondrial dysfunction induced H3K27ac during neurodegeneration in ex vivo models of PD. Our results reveal an exciting axis of ‘exposure/mutation-mitochondrial dysfunction-metabolism-H3K27ac-transcriptome’ for PD pathogenesis. Collectively, the novel mechanistic insights presented here interlinks mitochondrial dysfunction to epigenetic transcriptional regulation in dopaminergic degeneration as well as offer potential new epigenetic intervention strategies for PD.

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