scholarly journals MicroRNA-21 Negatively Regulates Treg Cells Through a TGF-β1/Smad-Independent Pathway in Patients with Coronary Heart Disease

2015 ◽  
Vol 37 (3) ◽  
pp. 866-878 ◽  
Author(s):  
Sihui Li ◽  
Qian Fan ◽  
Shaolin He ◽  
Tingting Tang ◽  
Yuhua Liao ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Pain Syndrome ◽  
Treg Cells ◽  
Protective Role ◽  
Negative Control ◽  
Peripheral Blood Mononuclear ◽  
Tgf Β1

Background: CD4+CD25+FoxP3+ regulatory T cells (Treg cells) play a protective role against the development and progression of the inflammatory disease atherosclerosis (AS). MicroRNA-21 (miR-21) is expressed in Treg cells and is up-regulated in the context of AS and other inflammatory diseases. Aims: This study aimed to determine the role of miR-21 in Treg cell regulation and gene expression during the development of AS in patients with coronary heart disease (CHD). Methods and Results: MiR-21 expression in peripheral blood mononuclear cells (PBMCs) was significantly up-regulated in patients with CHD (acute myocardial infarction (AMI) group, n=24; unstable angina (UA) group, n=21; stable angina (SA) group, n=24) compared with patients with chest pain syndrome (CPS, n=27), and miR-21 expression showed an increasing trend from SA to UA to AMI patients. Moreover, flow cytometry analysis indicated that the frequencies of circulating Treg cells decreased in a manner proportionate opposite with the level of miR-21. Quantitative real-time PCR (qRT-PCR) revealed a decrease in mRNA expression of forkhead box P3 (foxp3), transforming cell growth factor beta 1(TGF-β1) and smad7 (a known target gene of miR-21). ELISA analysis revealed a decrease in TGF-β1 secreted into the plasma. In addition, we transfected PBMCs with a miRNA negative control (NS-m), a miR-21 mimic (miR-21-m), a miRNA inhibitor negative control (NS-i), or a miR-21 inhibitor(miR-21-i). Up-regulation of miR-21 decreased the frequency of circulating Treg cells, decreased the expression levels of foxp3, TGF-β1 and smad7, and decreased the amount of TGF-β1 secreted into the plasma. Consistent with these observations, miR-21 down-regulation increased the frequency of circulating Treg cells, increased the expression of foxp3, TGF-β1 and smad7, and increased the amount of TGF-β1 secreted into the plasma. Conclusions: Because the smad7 expression pattern was similar to that of TGF-β, our study suggests that miR-21 can negatively regulate the frequency of circulating Treg cells through a TGF-β1/smad-independent signaling pathway in PBMCs.

Circular RNA expression profiles and bioinformatic analysis in coronary heart disease

Epigenomics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 439-454 ◽  
Author(s):  
Fangpu Yu ◽  
Yuanyuan Tie ◽  
Ya Zhang ◽  
Zunzhe Wang ◽  
Liwen Yu ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Coronary Arteries ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Peripheral Blood Mononuclear ◽  
Qrt Pcr ◽  
Blood Mononuclear Cells

Aim: We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary heart disease (CHD). Materials & methods: We performed sequence analysis of circRNAs in peripheral blood mononuclear cells of 70 CHD patients and 30 controls. Eight selected circRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in human atherosclerotic coronary arteries. Results: In total, 2283 downregulated and 85 upregulated circRNAs were identified in CHD. Parental genes of top 100 dysregulated-circRNAs are related to metabolism and protein modification, and 12 circRNAs might upregulate their CHD-related parental genes through miRNA sponges. Of the eight circRNAs validated in atherosclerotic coronary arteries by qRT-PCR, six were consistent with sequencing results of peripheral blood mononuclear cells. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in CHD pathophysiology.

Wine and Grape Juice Modulate Interferon-y-induced Neopterin Production and Tryptophan Degradation in Human PBMC

Pteridines ◽  
2004 ◽  
Vol 15 (1) ◽  
pp. 1-9 ◽  
Author(s):  
Gabriele Neurauter ◽  
Barbara Wirleitner ◽  
Katharina Schroecksnadel ◽  
Harald Schennach ◽  
Dietmar Fuchs
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Heart Diseases ◽  
Grape Juice ◽  
Alcoholic Beverages ◽  
Peripheral Blood Mononuclear ◽  
White Wines ◽  
Tryptophan Degradation

Abstract Population-based studies suggest moderate and regular consumption of alcoholic beverages and especially of red wine to reduce morbidity and mortality from coronary heart disease. These beverages may interfere with immune activation cascades crucial in the pathogenesis of coronary heart diseases. Neopterin concentrations in human body tluids were found to increase in the course of coronary heart disease indicating the activity of the atherogenetic process. In this study, human peripheral blood mononuclear cells (PBMC) stimulated with mitogens phytohaemagglutinin and concanavalin A were exposed to red and white wines, to ethanol and to grape juice as a non-alcoholic control in vitro. Neopterin production and tryptophan degradation were measured in supcrnalants. Both biochemical effects are induced by Th 1-type cytokine interferon-y and allow monitoring of immune actnation. In stimulated PBMC increased production of neopterin and degradation of tryptophan was observed Red and white wines, as well as grape juice inhibited these stimulation-induced effects, higher concentrations being more cffective. Ethanol had comparably small if any effect, Red and white wines as well as grape juice down regulate cytokine-mediated effects in PBMC. Most likely, antioxidant ingredients of wine and grape juice such as resveratrol are capable of interfering with immunologic pathways which appear to be of relevance, e g.. in the pathogenesis of cardiovascular disease.

scholarly journals Differentiation of T-helper cells in distinct phases of atopic dermatitis involves Th1/Th2 and Th17/Treg

2017 ◽  
Vol 15 (1) ◽  
pp. 46-52 ◽  
Author(s):  
Chuanli Su ◽  
Tao Yang ◽  
Zhihong Wu ◽  
Jiang Zhong ◽  
Yunshu Huang ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Mononuclear Cells ◽  
Treg Cells ◽  
Th2 Cells ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Th Cell ◽  
Blood Mononuclear Cells ◽  
Ifn Γ ◽  
Tgf Β1

The aim of this article is to study T-helper (Th) cell differentiation in the progression of acute, subacute, and chronic atopic dermatitis. Skin biopsies from 48 patients with acute, subacute, and chronic atopic dermatitis were studied using immunohistochemistry with antibodies to TARC/CCL17, CTACK/CCL27, and RANTES/CCL5. Peripheral blood mononuclear cells were studied in 17 patients using flow cytometry to measure the content of Th1/Th2 cells and Th17/Treg cells. Levels of interferon (IFN)-γ, interleukin (IL)-4, IL-17A, and transforming growth factor (TGF)-β1 were evaluated with enzyme-linked immunosorbent assay (ELISA). Distinctive expressions of T-cell-specific chemokines TARC/CCL17, CTACK/CCL27, and RANTES/CCL5 were observed at different stages of atopic dermatitis, which were consistent with the differentiation of the Th cell subsets, Th2/Th1, and Th17/Treg. Th2 and Th17 were acute-phase subsets, while Th1 and Treg were chronic-phase subsets. At an early stage of atopic dermatitis, Th17 and Th2 cells were found in peripheral blood mononuclear cells, followed by Th1 cells, Treg cells, and eosinophils; in late-stage or subacute and chronic atopic dermatitis, Th17 and Th2 cell numbers decreased. The levels of the IFN-γ and TGF-β1 increased during the progression of atopic dermatitis from acute to chronic forms. The levels of IL-17A and IL-4 decreased during the progression of atopic dermatitis from acute to chronic forms. The differentiation of Th subsets at distinct phases in atopic dermatitis may form the basis for further studies on the classification or control of this increasingly common clinical condition.

scholarly journals Identification of Promiscuous African Swine Fever Virus T-Cell Determinants Using a Multiple Technical Approach

Vaccines ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 29
Author(s):  
Laia Bosch-Camós ◽  
Elisabet López ◽  
María Jesús Navas ◽  
Sonia Pina-Pedrero ◽  
Francesc Accensi ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
African Swine Fever Virus ◽  
African Swine Fever ◽  
Cd8 T Cell ◽  
Protective Role ◽  
Full Length ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear

The development of subunit vaccines against African swine fever (ASF) is mainly hindered by the lack of knowledge regarding the specific ASF virus (ASFV) antigens involved in protection. As a good example, the identity of ASFV-specific CD8+ T-cell determinants remains largely unknown, despite their protective role being established a long time ago. Aiming to identify them, we implemented the IFNγ ELISpot as readout assay, using as effector cells peripheral blood mononuclear cells (PBMCs) from pigs surviving experimental challenge with Georgia2007/1. As stimuli for the ELISpot, ASFV-specific peptides or full-length proteins identified by three complementary strategies were used. In silico prediction of specific CD8+ T-cell epitopes allowed identifying a 19-mer peptide from MGF100-1L, as frequently recognized by surviving pigs. Complementarily, the repertoire of SLA I-bound peptides identified in ASFV-infected porcine alveolar macrophages (PAMs), allowed the characterization of five additional SLA I-restricted ASFV-specific epitopes. Finally, in vitro stimulation studies using fibroblasts transfected with plasmids encoding full-length ASFV proteins, led to the identification of MGF505-7R, A238L and MGF100-1L as promiscuously recognized antigens. Interestingly, each one of these proteins contain individual peptides recognized by surviving pigs. Identification of the same ASFV determinants by means of such different approaches reinforce the results presented here.

Meta-inflammation in monocytes of patients with Acute Coronary Syndrome

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
F Canonico ◽  
R Vinci ◽  
D Pedicino ◽  
E Pisano ◽  
P Ciampi ◽  
...  
Keyword(s):  
Protein Identification ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Glycolytic Enzyme ◽  
Potential Interaction ◽  
Limiting Factor ◽  
Funding Source ◽  
Peripheral Blood Mononuclear ◽  
Coronary Syndrome ◽  
Key Enzyme

Abstract Background Several studies suggest that an alteration of monocyte metabolism might be implicated in inflammatory diseases. Enhanced glycolysis might be a hallmark of pro-inflammatory monocyte subsets. Improved glycolysis enables the immune cells to generate sufficient ATP and biosynthetic intermediates to carry out its particular effector functions. For macrophages this includes phagocytosis and inflammatory cytokine production. Pyruvate Kinase isozyme M2 (PKM-2) catalyzes the final step of glycolysis producing pyruvate and ATP. Latest studies have shown that a member of Jumonji family (JMJD8) acts as a positive regulator in TNF-induced NF-kB signaling leading to pro-inflammatory pathways in macrophages and is involved in angiogenesis and cellular metabolism through interacting with PKM-2 in endothelial cells. Purpose The aims of the study are to assess the expression of the glycolytic key enzyme PKM-2 in CD14+ monocytes obtained from patients with non-ST-elevation myocardial infarction (NSTEMI) or with stable angina (SA). Furthermore, the expression of JMJD8 was evaluated. Methods 30 patients with NSTEMI and 30 patients with SA were enrolled. Peripheral blood mononuclear cells were obtained from whole blood samples. For cytoplasmatic protein identification, cells were fixed and permeabilized and then incubated with fluorochrome-conjugated mAbs anti-CD14, anti-PKM-2 and anti-JMJD8. For analysis we used Two-tailed Mann-Whitney non parametric Comparison test. Results CD14+ monocytes from NSTEMI patients showed reduced expression of the key glycolytic enzyme PKM-2 as compared to CD14+ monocytes from SA patients (p=0.02) (Figure 1). JMJD8 expression in NSTEMI patients is increased compared with SA patients (p=0.02) (Figure 2). Conclusion This study introduces a role for immune-metabolism in the immunity dysregulation described in ACS patients and provides novel insights into the mechanisms responsible for coronary instability. Taking their potential interaction into account, our data suggest that in acute setting glycolysis key enzyme PKM2 expression is downregulated. Besides, JMJD8 protein levels increase in NSTEMI patients acting as potential limiting factor of PKM2 function. Moreover, our data propose the potential roles of immune-metabolism to detect novel therapeutic targets, associated with an accurate patient stratification based on immune-metabolic profiles, for prevention and treatment of atherosclerosis, in the perspective of a personalized medicine approach. Funding Acknowledgement Type of funding source: Private hospital(s). Main funding source(s): Fondazione Policlinico A. Gemelli

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