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.

Molecular Biomarkers of Anti-TNF Response in Patients with Rheumatoid Arthritis

2020 ◽  
Author(s):  
Niyaz Yoosuf ◽  
Mateusz Maciejewski ◽  
Daniel Ziemek ◽  
Scott Jelinsky ◽  
Lasse Folkersen ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Flow Cytometry ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Treatment Initiation ◽  
Cell Types ◽  
Proteomics Data ◽  
Peripheral Blood Mononuclear ◽  
Before And After

Abstract BackgroundAdvances in immunotherapy by blocking TNF have remarkably improved treatment outcomes for rheumatoid arthritis (RA) patients. Although treatment specifically targets TNF-α, the downstream mechanisms of immune suppression are not completely understood, and the reason for the reduced efficacy in a significant fraction of patients remains unclear. Hence this study was designed to detect biomarkers and expression signatures of response to TNF inhibition.MethodsIn this study, we included 39 female patients diagnosed with RA who were non-responders to methotrexate treatment. The blood samples were collected before anti-TNF treatment initiation, and three months into treatment. The clinical evaluations were performed based on European League Against Rheumatism (EULAR) and classified 23 patients as responders and 16 as non-responders after three months following the initiation of anti-TNF treatment. We investigated differences in gene expression in peripheral blood mononuclear cells (PBMCs), the proportion of cell types and cell phenotypes in peripheral blood using flow cytometry, the level of proteins in serum, as well as clinical and demographic factors.ResultsWe performed analyses to identify differences between responders and non-responders at both time points (before and after treatment initiation) as well as to detect the changes induced during the treatment using transcriptomics, flow cytometry and proteomics data. The gene expression analysis before treatment revealed notably a higher expression of EPPK1 and BCL6-AS1 in future responders. We further detected suppression of genes and proteins during treatment, most notably a suppression of expression of the gene, T-cell inhibitor CHI3L1 and its protein YKL-40 measured from flow cytometry. We identified an increase in the proportion of T- and B cells, whereas the proportion of granulocytes was suppressed during treatment in responders. Finally, our machine learning models mainly based on transcriptomics data showed high predictive utility (ROC AUC ± SEM: 0.81 ± 0.17) in classifying response before anti-TNF treatment initiation.ConclusionsOur comprehensive analyses resulted in several useful insights regarding the transcriptional and translational regulations of anti-TNF treatment in RA patients. The study reports first transcriptomics analysis using RNA sequencing of isolated PBMCs from anti-TNF naïve and anti-TNF treated RA patients to study biomarkers and predict anti-TNF response.

scholarly journals Differential Expression of MMP2 and TIMP2 in Peripheral Blood Mononuclear Cells After Roux-en-Y Gastric Bypass

2021 ◽  
Vol 8 ◽  
Author(s):  
Carla Barbosa Nonino ◽  
Natália Yumi Noronha ◽  
Maysa de Araújo Ferreira-Julio ◽  
Lígia Moriguchi Watanabe ◽  
Karen Francislaine Cassia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Weight Loss ◽  
Gastric Bypass ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Ecm Remodeling ◽  
Blood Mononuclear Cells ◽  
Before And After

Matrix metalloproteinases (MMP) and their endogenous inhibitor, the tissue inhibitor of metalloproteinases (TIMP), are expressed in many different cell types and play an important role in physiologic and pathological degradation of extracellular matrix (ECM). Starting from these observations and considering the activation state of peripheral blood mononuclear cells (PBMCs) in obesity, we investigated the gene expression of metalloproteinases before and after Roux-en-Y gastric bypass (RYBG). The study was performed in the Ribeirão Preto Medical School University Hospital. Seventy-three women were divided into a study group (SG), composed of 53 individuals with severe obesity before and after 6 months of RYGB, and a control group (CG), composed of 20 normal-weight individuals. Anthropometric and body composition data were collected, and peripheral blood for ribonucleic acid (RNA) extraction. The biological samples were submitted to a quantitative real-time polymerase chain reaction to evaluate the expression of MMP2 and TIMP2 genes. Alterations in weight loss, body mass index (BMI), and fat mass (FM) were observed after 6 months of RYGB (p &lt; 0.05). A reduction of gene expression of TIMP2 was observed after 6 months of RYGB, contributing positively to the weight loss (R2 = 0.33 p = 0.04). The enrichment analyses highlighted the interaction between TIMP2 and MMP2 genes and the molecular pathways involving the ECM remodeling in the obesity condition. RYGB contributes significantly to weight loss, improved BMI, reduced FM, and reduced TIMP2 expression in PBMCs, which might contribute to the ECM remodeling in the obesity and could be useful as a circulating biomarker.

scholarly journals Expression Profiling of Transcriptome and Its Associated Disease Risk in Yang Deficiency Constitution of Healthy Subjects

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ruoxi Yu ◽  
Yin Yang ◽  
Yuanyuan Han ◽  
Pengwei Hou ◽  
Yingshuai Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Clinical Medicine ◽  
Disease Risk ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Molecular Evidence ◽  
Chinese Han ◽  
Peripheral Blood Mononuclear

Objectives. Differences among healthy subjects and associated disease risks are of substantial interest in clinical medicine. According to the theory of “constitution-disease correlation” in traditional Chinese medicine, we try to find out if there is any connection between intolerance of cold in Yang deficiency constitution and molecular evidence and if there is any gene expression basis in specific disorders. Methods. Peripheral blood mononuclear cells were collected from Chinese Han individuals with Yang deficiency constitution (n=20) and balanced constitution (n=8) (aged 18–28) and global gene expression profiles were determined between them using the Affymetrix HG-U133 Plus 2.0 array. Results. The results showed that when the fold change was ≥1.2 and q ≤ 0.05, 909 genes were upregulated in the Yang deficiency constitution, while 1189 genes were downregulated. According to our research differential genes found in Yang deficiency constitution were usually related to lower immunity, metabolic disorders, and cancer tendency. Conclusion. Gene expression disturbance exists in Yang deficiency constitution, which corresponds to the concept of constitution and gene classification. It also suggests people with Yang deficiency constitution are susceptible to autoimmune diseases, enteritis, arthritis, metabolism disorders, and cancer, which provides molecular evidence for the theory of “constitution-disease correlation.”

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 Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise

2011 ◽  
Vol 43 (14) ◽  
pp. 895-902 ◽  
Author(s):  
Lindsey B. Gano ◽  
Anthony J. Donato ◽  
Gary L. Pierce ◽  
Hamza M. Pasha ◽  
Katherine A. Magerko ◽  
...  
Keyword(s):  
Gene Expression ◽  
Older Adults ◽  
Aerobic Exercise ◽  
Exercise Intervention ◽  
Mononuclear Cells ◽  
Maximal Oxygen Consumption ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Maximal Heart Rate ◽  
Peripheral Blood Mononuclear ◽  
Monocyte Chemoattractant Protein 1

We tested the hypothesis that peripheral blood mononuclear cells (PBMC) of older adults demonstrate a proinflammatory/-oxidative gene expression profile that can be improved by regular aerobic exercise. PBMC were isolated from young ( n = 25, 18–33 yr) and middle-aged/older ( n = 40, 50–76 yr) healthy adults. The older adults had greater mRNA expression (real-time RT-PCR) of the proinflammatory/-oxidant transcription factor nuclear factor-κB (1.58-fold, P < 0.05) and receptor for advanced glycation end products (1.12-fold, P < 0.05), the proinflammatory cytokines tumor necrosis factor-α (1.90-fold, P < 0.05) and monocyte chemoattractant protein-1 (1.47-fold, P < 0.05), and the oxidant-producing enzymes nicotinamide adenine dinucleotide phosphate-oxidase (0.91-fold, P < 0.05) and inducible nitric oxide synthase (2.60-fold, P < 0.05). In 11 subjects (58–70 yr), maximal oxygen consumption (+11%) and exercise time (+19%) were increased (both P < 0.001), and expression of the above proinflammatory/-oxidative genes was or tended to be decreased in PBMC after vs. before 2 mo of aerobic exercise (brisk walking ∼6 days/wk, 50 min/day, 70% of maximal heart rate). Expression of interleukin-6 was not different with age or exercise intervention. Age group- and exercise intervention-related differences in gene expression were independent of other factors. PBMC of healthy older adults demonstrate increased expression of several genes associated with inflammation and oxidative stress, which is largely ameliorated by habitual aerobic exercise. This proinflammatory/-oxidative gene signature may represent a therapeutic target for lifestyle and pharmacological prevention and treatment strategies.

scholarly journals Peripheral Blood Gene Expression and IgG Glycosylation Profiles as Markers of Tocilizumab Treatment in Rheumatoid Arthritis

2012 ◽  
Vol 39 (5) ◽  
pp. 916-928 ◽  
Author(s):  
BERTALAN MESKO ◽  
SZILARD POLISKA ◽  
SZILVIA SZAMOSI ◽  
ZOLTAN SZEKANECZ ◽  
JANOS PODANI ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Peripheral Blood ◽  
Multiple Testing ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Quantitative Polymerase Chain Reaction ◽  
Response To Treatment ◽  
Peripheral Blood Mononuclear ◽  
Gene Sets

Objective.Tocilizumab, a humanized anti-interleukin-6 receptor monoclonal antibody, has recently been approved as a biological therapy for rheumatoid arthritis (RA) and other diseases. It is not known if there are characteristic changes in gene expression and immunoglobulin G glycosylation during therapy or in response to treatment.Methods.Global gene expression profiles from peripheral blood mononuclear cells of 13 patients with RA and active disease at Week 0 (baseline) and Week 4 following treatment were obtained together with clinical measures, serum cytokine levels using ELISA, and the degree of galactosylation of the IgG N-glycan chains. Gene sets separating responders and nonresponders were tested using canonical variates analysis. This approach also revealed important gene groups and pathways that differentiate responders from nonresponders.Results.Fifty-nine genes showed significant differences between baseline and Week 4 and thus correlated with treatment. Significantly, 4 genes determined responders after correction for multiple testing. Ten of the 12 genes with the most significant changes were validated using real-time quantitative polymerase chain reaction. An increase in the terminal galactose content of N-linked glycans of IgG was observed in responders versus nonresponders, as well as in treated samples versus samples obtained at baseline.Conclusion.As a preliminary report, gene expression changes as a result of tocilizumab therapy in RA were examined, and gene sets discriminating between responders and nonresponders were found and validated. A significant increase in the degree of galactosylation of IgG N-glycans in patients with RA treated with tocilizumab was documented.

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