scholarly journals Differential Expression of Apoptotic and Low-Grade Inflammatory Markers in Alzheimer Disease Compared to Diabetes Mellitus Type 1 and 2

2019 ◽  
Vol 3 (6) ◽  
pp. 1003-1013 ◽  
Author(s):  
Krystallenia I Alexandraki ◽  
Nikolaos V Apostolopoulos ◽  
Christos Adamopoulos ◽  
Evangelia Stamouli ◽  
Georgia Dalagiorgou ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Fas Ligand ◽  
Mononuclear Cells ◽  
Plasma Concentrations ◽  
Diabetes Mellitus Type 1 ◽  
Low Grade ◽  
Peripheral Blood Mononuclear ◽  
Reactive Protein ◽  
Before And After

Abstract Background Neuroinflammation, impaired brain insulin signaling, and neuronal apoptosis may be interrelated in the pathophysiology of people with Alzheimer disease (AD) and diabetes, either type 1 or 2 diabetes (T1D or T2D, respectively). Methods We studied 116 patients: 41 with AD, 20 with T1D, 21 with T2D, and 34 healthy controls. The number (n) of cytokine-secreting peripheral blood mononuclear cells (PBMCs) before and after mitogenic stimulation was determined for interleukin 1β (IL1β), interleukin 6 (IL6), tumor necrosis factor (TNF) by the enzyme-linked-immuno-spot assay. Serum concentrations of C-reactive protein (CRP) and Fas ligand (FASLG) were determined by ELISA. Results The studied subgroups did not differ in sex but differed in age. Higher CRP concentrations were detected in the AD group than in the T1D group (P = 0.02) and lower in controls (P < 0.001). The nPBMCs was higher in AD patients after stimulation than in basal conditions: after stimulation in nTNF (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.001 vs control), nIL6 (P = 0.039 vs T2D; P < 0.001 vs T1D; P = 0.007 vs control), and nIL1β (P = 0.03 vs control). The nPBMCs increased after stimulation with ΡΜA in all the subgroups (P < 0.001). FASLG in the AD group displayed statistically higher concentrations than in all other subgroups (P < 0.001 vs T2D; P < 0.001 vs T1D; P = 0.012 vs control). The nPBMCs was positively correlated with plasma concentrations of FASLG in the AD subgroup. Conclusions Patients with AD display a low-grade systemic inflammation compared to people with diabetes. The FAS–FASLG pathway has a potential role because FASLG concentrations are positively correlated with the inflammatory response in AD. However, this positive correlation cannot be seen in people with diabetes, at least not with the apoptotic markers used in the present study.

scholarly journals Increased levels of circulating LPS during Tuberculosis prevails in patients with advanced pulmonary involvement

PLoS ONE ◽  
2021 ◽  
Vol 16 (9) ◽  
pp. e0257214
Author(s):  
Georgina Gallucci ◽  
Natalia Santucci ◽  
Ariana Díaz ◽  
Bettina Bongiovanni ◽  
Diego Bértola ◽  
...  
Keyword(s):  
Mononuclear Cells ◽  
Plasma Concentrations ◽  
Pulmonary Involvement ◽  
C Reactive Protein ◽  
Proinflammatory Response ◽  
Peripheral Blood Mononuclear ◽  
Reactive Protein ◽  
Gastrointestinal Bacteria ◽  
Elisa Technique ◽  
Ifn Γ

Our earlier studies in tuberculosis (TB) patients indicate that in those where the process evolves to a larger pulmonary involvement, the immune endocrine response may promote an unfavorable environment. Chronic infectious diseases, and their persistent proinflammatory response, may affect mucosal barriers integrity favoring the translocation of gastrointestinal bacteria, leading to an increase of circulating lipopolysaccharides (LPS). Consequently, we quantified LPS levels in TB patients, with different degrees of pulmonary involvement, and controls (Co) and analyzed the possible relationship between LPS and inflammatory mediators i.e., C reactive protein (CRP), interleukin 6 (IL-6) and Interferon-gamma (IFN-γ), Erythrocyte Sedimentation Rate (ESR), steroid hormones (Cortisol and Dehydroepiandrosterone, DHEA), and inflammatory transcripts from peripheral blood mononuclear cells (IL-1β, IL-6, IFN-γ). LPS was assessed by the Limulus amoebocyte lysate assay and the ELISA technique was used to quantify hormones and cytokines in the plasma samples. Cytokine transcripts from PBMC were evaluated by qRT-PCR. Non-parametric tests were used. LPS levels were increased in TB patients, as did levels of CRP, IL-6, IFN-γ, cortisol and ESR. Severe patients had the highest amounts of circulating LPS; with moderate and severe cases showing much higher levels of CRP, ESR, IL-6, IFN-γ and cortisol/DHEA ratio, as an endocrine imbalance. Only in PBMC from severe cases was mRNA for IL-1β increased. Correlation analysis showed that levels of LPS from severe patients were positively associated with IL-6 and IFN-γ plasma concentrations and with IL-1β transcripts, while IL-6 had a positive correlation with the cortisol/DHEA ratio. The higher levels of circulating LPS during progressive TB may emerge as a contributing factor for the persistence of the greater immune endocrine imbalance distinctive of advanced disease, which might suggest a vicious cycle among LPS, inflammation and endocrine imbalance.

Expression of Nod-Like Receptor Protein 3 (NLRP3) in Peripheral Blood Mononuclear Cells of Patients with Sepsis

2020 ◽  
Vol 10 (2) ◽  
pp. 271-275
Author(s):  
Ying Li ◽  
Yongshan Tang
Keyword(s):  
Immune Responses ◽  
Mononuclear Cells ◽  
Receptor Protein ◽  
Control Group ◽  
C Reactive Protein ◽  
Peripheral Blood Mononuclear ◽  
Reactive Protein ◽  
Adaptive Immune ◽  
Caspase 1 ◽  
Before And After

Sepsis is a common clinical disease. The NLRP3 inflammasome is a multiprotein complex that is involved in both innate and adaptive immune responses. However, the expression of NLRP3 in patients with sepsis has not been elucidated. 98 patients with sepsis before and after treatment were selected and 106 healthy volunteers were used as the control group. PBMCs were isolated from each group to measure NLRP3 and Caspase 1 level Real time PCR. The expression of serum procalcitonin (PCT), C-reactive protein (CRP), IL-1β and IL-18 was analyzed by ELISA. NLRP3 and Caspase 1 level was significantly increased in sepsis patients before treatment with increased secretion of IL-1β and IL-18 in serum and elevated level of PCT and CRP (P < 0.05). NLRP3, Caspase 1 expression, IL-1β and IL-18 secretion were positively correlated with serum PCT and CRP in patients with sepsis (P < 0.05). After treatment, NLRP3 and Caspase 1 mRNA expression was significantly decreased and serum IL-1β and IL-18 secretion was significantly decreased (P < 0.05). NLRP3 is increased in sepsis and IL-1β and IL-18 secretion is elevated, implying the involvement of NLRP3 in the occurrence and development of sepsis.

Cortisol-induced CXCR4 augmentation mobilizes T lymphocytes after acute physical stress

2005 ◽  
Vol 288 (3) ◽  
pp. R591-R599 ◽  
Author(s):  
Mitsuharu Okutsu ◽  
Kenji Ishii ◽  
Kai Jun Niu ◽  
Ryoichi Nagatomi
Keyword(s):  
T Lymphocytes ◽  
Mononuclear Cells ◽  
Cxcr4 Expression ◽  
Peripheral Blood Mononuclear ◽  
Cycling Exercise ◽  
Ru 486 ◽  
Before And After ◽  
Stromal Cell Derived Factor ◽  
Chemokine Receptor 4

The aim of this study was to elucidate the mechanism responsible for lymphopenia after exercise. Seven young healthy men volunteered for this study. Peripheral blood mononuclear cells (PBMC) were cultured with cortisol and analyzed for C-X-C motif chemokine receptor 4 (CXCR4) expression by flow cytometry. To determine the effects of exercise, subjects performed exhaustive cycling exercise. PBMC were cultured with plasma obtained before and after the cycling exercise. Alternatively, PBMC obtained before and after exercise were cultured without plasma or glucocorticoid to examine whether PBMC were primed in vivo for CXCR4 expression. We analyzed cortisol- or plasma-treated PBMC to determine their ability to migrate through membrane filters in response to stromal cell-derived factor 1α/CXCL12. Cortisol dose- and time-dependently augmented CXCR4 expression on T lymphocytes, with <6 h of treatment sufficient to augment CXCR4 on T lymphocytes. Postexercise plasma also augmented CXCR4 expression. Cortisol or postexercise plasma treatment markedly enhanced migration of T lymphocytes toward CXCL12. Augmentation of CXCR4 on T lymphocytes by cortisol or plasma was effectively blocked by the glucocorticoid receptor antagonist RU-486. Thus exercise-elicited endogenous cortisol effectively augments CXCR4 expression on T lymphocytes, which may account for lymphopenia after exercise.

scholarly journals Activation of Peripheral Blood Mononuclear Cells and Leptin Secretion: New Potential Role of Interleukin-2 and High Mobility Group Box (HMGB)1

2021 ◽  
Vol 22 (15) ◽  
pp. 7988
Author(s):  
Andrea Coppola ◽  
Barbara Capuani ◽  
Francesca Pacifici ◽  
Donatella Pastore ◽  
Roberto Arriga ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Interleukin 2 ◽  
High Mobility ◽  
High Mobility Group ◽  
Low Grade ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Activation of innate immunity and low-grade inflammation contributes to hyperglycemia and an onset of Type 2 Diabetes Mellitus (T2DM). Interleukin-2 (IL-2), leptin, High Mobility Group Box-1 (HMGB-1), and increased glucose concentrations are mediators of these processes also by modulating peripheral blood mononuclear cells (PBMCs) response. The aim of this study was to investigate if HMGB-1 and IL-2 turn on PBMCs and their leptin secretion. In isolated human PBMCs and their subpopulations from healthy individuals and naïve T2DM patients, leptin release, pro-inflammatory response and Toll-like Receptors (TLRs) activation was measured. After treatment with IL-2 and HMGB1, NK (Natural Killer) have the highest amount of leptin secretion, whilst NK-T have the maximal release in basal conditions. TLR4 (TAK242) and/or TLR2 (TLR2-IgA) inhibitors decreased leptin secretion after IL-2 and HMGB1 treatment. A further non-significant increase in leptin secretion was reported in PBMCs of naive T2DM patients in response to IL-2 and HMGB-1 stimulation. Finally, hyperglycemia or hyperinsulinemia might stimulate leptin secretion from PBMCs. The amount of leptin released from PBMCs after the different treatments was enough to stimulate the secretion of IL-1β from monocytes. Targeting leptin sera levels and secretion from PBMCs could represent a new therapeutic strategy to counteract metabolic diseases such as T2DM.

scholarly journals Effects of 30 min of aerobic exercise on gene expression in human neutrophils

2008 ◽  
Vol 104 (1) ◽  
pp. 236-243 ◽  
Author(s):  
Shlomit Radom-Aizik ◽  
Frank Zaldivar ◽  
Szu-Yun Leu ◽  
Pietro Galassetti ◽  
Dan M. Cooper
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Cycle Ergometer ◽  
Human Neutrophils ◽  
Peripheral Blood Mononuclear ◽  
False Discovery ◽  
Ergometer Exercise ◽  
Before And After ◽  
Ease Score ◽  
Repair Genes

Relatively brief bouts of exercise alter gene expression in peripheral blood mononuclear cells (PBMCs), but whether exercise changes gene expression in circulating neutrophils (whose numbers, like PBMCs, increase) is not known. We hypothesized that exercise would activate neutrophil genes involved in apoptosis, inflammation, and cell growth and repair, since these functions in leukocytes are known to be influenced by exercise. Blood was sampled before and immediately after 30 min of constant, heavy (∼80% peak O2uptake) cycle ergometer exercise in 12 healthy men (19–29 yr old) of average fitness. Neutrophils were isolated using density gradients; RNA was hybridized to Affymetrix U133+2 Genechip arrays. With false discovery rate (FDR) <0.05 with 95% confidence, a total of 526 genes were differentially expressed between before and after exercise. Three hundred and sixteen genes had higher expression after exercise. The Jak/STAT pathway, known to inhibit apoptosis, was significantly activated (EASE score, P < 0.005), but 14 genes were altered in a way likely to accelerate apoptosis as well. Similarly, both proinflammatory (e.g., IL-32, TNFSF8, and CCR5) and anti-inflammatory (e.g., ANXA1) were affected. Growth and repair genes like AREG and FGF2 receptor genes (involved in angiogenesis) were also activated. Finally, a number of neutrophil genes known to be involved in pathological conditions like asthma and arthritis were altered by exercise, suggesting novel links between physical activity and disease or its prevention. In summary, brief heavy exercise leads to a previously unknown substantial and significant alteration in neutrophil gene expression.

Exercise elevates plasma levels but not gene expression of IL-1β, IL-6, and TNF-α in blood mononuclear cells

2000 ◽  
Vol 89 (4) ◽  
pp. 1499-1504 ◽  
Author(s):  
Andrei I. Moldoveanu ◽  
Roy J. Shephard ◽  
Pang N. Shek
Keyword(s):  
Gene Expression ◽  
Oxygen Uptake ◽  
Mononuclear Cells ◽  
Plasma Concentrations ◽  
Peak Oxygen Uptake ◽  
Cytokine Gene Expression ◽  
Mrna Accumulation ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells

Physical activity induces a subclinical inflammatory response, mediated in part by leukocytes, and manifested by elevated concentrations of circulating proinflammatory cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α (TNF-α). However, the source of the cytokines that appear during exercise remains unknown. In this study, we examined exercise-induced changes in plasma cytokine concentrations and their corresponding mRNA expression in peripheral blood mononuclear cells. Ten healthy [peak oxygen uptake = 48.8 ± 6.5 (SD) ml · kg−1 · min−1] but untrained men [age = 25 ± 5 (SD) yr] undertook 3 h of exercise (cycling and inclined walking) at 60–65% peak oxygen uptake. Circulating leukocyte subset counts were elevated during and 2 h postexercise but returned to normal within 24 h. Plasma concentrations of IL-1β, IL-6, and TNF-α peaked at the end of exercise and remained elevated at 2 h (IL-6) and up to 24 h (IL-1β and TNF-α) postexercise. Cytokine gene expression in circulating mononuclear cells was measured by using the reverse transcriptase-polymerase chain reaction; mRNA accumulation did not change with exercise. In conclusion, mRNA accumulation of IL-1β, IL-6, and TNF-α in circulating mononuclear cells is not affected by 3 h of moderate endurance exercise and does not seem to account for the observed increases in plasma cytokines.

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