scholarly journals LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals with Diabetes

2021 ◽  
Author(s):  
Icaro Bonyek-Silva ◽  
Antônio Fernando Araújo Machado ◽  
Thiago Cerqueira-Silva ◽  
Sara Nunes ◽  
Márcio Rivison Silva Cruz ◽  
...  
Keyword(s):  
Intensive Care ◽  
Mononuclear Cells ◽  
Serum Levels ◽  
Low Grade ◽  
Receptor System ◽  
Peripheral Blood Mononuclear ◽  
Early Markers ◽  
Patients With Diabetes ◽  
Care Assistance ◽  
Low Grade Inflammation

Diabetes is a known risk factor for severe COVID-19, the disease caused by the new coronavirus SARS-CoV-2. However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. Therefore, we aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of hospitalized patients for COVID-19, with diabetes and without diabetes. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of SARS-CoV-2 main receptor system (<i>ACE2/TMPRSS2</i>) and main molecule of LTB<sub>4</sub> pathway (<i>ALOX5</i>). We found that diabetes activates LTB<sub>4</sub> pathway, and during COVID-19, it increases <i>ACE2/TMPRSS2</i> as well as <i>ALOX5</i> expression. Diabetes was also associated with COVID-19-related disorders, such as reduced SpO2/FiO2 and PaO2/FiO2 levels, and increased disease duration. In addition, the expression of <i>ACE2</i> and <i>ALOX5</i> are positively correlated, with increased expression in COVID-19 patients with diabetes requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB<sub>4</sub> is significantly increased in individuals with diabetes. Besides, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB<sub>4</sub> and IL-6 systemic levels, as well as, <i>ACE2</i><i>/ALOX5</i> blood expression could be early markers of severe COVID-19 in individuals with diabetes.

scholarly journals LTB4-Driven Inflammation and Increased Expression of ALOX5/ACE2 During Severe COVID-19 in Individuals with Diabetes

2021 ◽  
Author(s):  
Icaro Bonyek-Silva ◽  
Antônio Fernando Araújo Machado ◽  
Thiago Cerqueira-Silva ◽  
Sara Nunes ◽  
Márcio Rivison Silva Cruz ◽  
...  
Keyword(s):  
Intensive Care ◽  
Mononuclear Cells ◽  
Serum Levels ◽  
Low Grade ◽  
Receptor System ◽  
Peripheral Blood Mononuclear ◽  
Early Markers ◽  
Patients With Diabetes ◽  
Care Assistance ◽  
Low Grade Inflammation

Diabetes is a known risk factor for severe COVID-19, the disease caused by the new coronavirus SARS-CoV-2. However, there is a lack of knowledge about the mechanisms involved in the evolution of COVID-19 in individuals with diabetes. Therefore, we aimed to evaluate whether the chronic low-grade inflammation of diabetes could play a role in the development of severe COVID-19. We collected clinical data and blood samples of hospitalized patients for COVID-19, with diabetes and without diabetes. Plasma samples were used to measure inflammatory mediators and peripheral blood mononuclear cells, for gene expression analysis of SARS-CoV-2 main receptor system (<i>ACE2/TMPRSS2</i>) and main molecule of LTB<sub>4</sub> pathway (<i>ALOX5</i>). We found that diabetes activates LTB<sub>4</sub> pathway, and during COVID-19, it increases <i>ACE2/TMPRSS2</i> as well as <i>ALOX5</i> expression. Diabetes was also associated with COVID-19-related disorders, such as reduced SpO2/FiO2 and PaO2/FiO2 levels, and increased disease duration. In addition, the expression of <i>ACE2</i> and <i>ALOX5</i> are positively correlated, with increased expression in COVID-19 patients with diabetes requiring intensive care assistance. We confirmed these molecular results at the protein level, where plasma LTB<sub>4</sub> is significantly increased in individuals with diabetes. Besides, IL-6 serum levels are increased only in individuals with diabetes requiring intensive care assistance. Together, these results indicate that LTB<sub>4</sub> and IL-6 systemic levels, as well as, <i>ACE2</i><i>/ALOX5</i> blood expression could be early markers of severe COVID-19 in individuals with diabetes.

scholarly journals Acute Strenuous Exercise Induces an Imbalance on Histone H4 Acetylation/Histone Deacetylase 2 and Increases the Proinflammatory Profile of PBMC of Obese Individuals

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Gilson P. Dorneles ◽  
Maria Carolina R. Boeira ◽  
Lucas L. Schipper ◽  
Ivy R. V. Silva ◽  
Viviane R. Elsner ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Mononuclear Cells ◽  
Strenuous Exercise ◽  
Low Grade ◽  
Histone H4 ◽  
Peripheral Blood Mononuclear ◽  
Histone Deacetylase 2 ◽  
Histone H4 Acetylation ◽  
Low Grade Inflammation

This study evaluated the response of global histone H4 acetylation (H4ac), histone deacetylase 2 (HDAC2) activity, as well as the production of proinflammatory cytokines and monocyte phenotypes of lean and obese males after exercise. Ten lean and ten obese sedentary men were submitted to one session of strenuous exercise, and peripheral blood mononuclear cells (PBMC) were stimulated in vitro with lipopolysaccharide (LPS). Global H4ac levels, HDAC2 activity in PBMC, and IL-6, IL-8, and TNF-α production were analyzed. Monocyte phenotype was determined in accordance with the expression of CD14 and CD16. At rest, obese individuals presented higher frequency of proinflammatory CD14+CD16+ monocytes. LPS induced a significant augment in global H4ac and in the production of IL-6, IL-8, and TNF-α mainly in obese individuals. After exercise, the increased production of IL-8 and TNF-α and peripheral frequency of CD14+CD16+ were observed in both groups. In addition, exercise also induced a significant hyperacetylation of histone H4 and decreased HDAC2 activity in both nonstimulated and LPS-stimulated PBMC of obese individuals. Our data indicate that the obesity impacts on H4ac levels and that strenuous exercise leads to an enhanced chronic low-grade inflammation profile in obesity via an imbalance on H4ac/HDAC2.

Increased Serum Interleukin 22 in Patients with Rheumatoid Arthritis and Correlation with Disease Activity

2012 ◽  
Vol 39 (7) ◽  
pp. 1320-1325 ◽  
Author(s):  
LAURINDO FERREIRA da ROCHA ◽  
ÂNGELA LUZIA BRANCO PINTO DUARTE ◽  
ANDRÉA TAVARES DANTAS ◽  
HENRIQUE ATAÍDE MARIZ ◽  
IVAN da ROCHA PITTA ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Mononuclear Cells ◽  
Activity Index ◽  
Elevated Serum ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Additional Tool ◽  
Bone Erosions ◽  
Interleukin 22

Objective.To analyze the role of interleukin 22 (IL-22) in rheumatoid arthritis (RA).Methods.IL-22 serum levels were measured in 83 patients with established RA under treatment with disease-modifying antirheumatic drugs and in 30 healthy controls matched for age and sex. Patients were assessed for clinical and laboratory variables. Correlations of IL-22 serum levels with disease activity measures [Clinical Disease Activity Index (CDAI) and Disease Activity Score for 28 joints (DAS28)], serological markers, bone erosions, and demographic factors were assessed. Peripheral blood mononuclear cells (PBMC) from 30 patients with RA and 14 controls were purified and stimulatedin vitrowith phorbol myristate acetate (PMA)/ionomycin. IL-22 production by PBMC and in serum was investigated by ELISA.Results.IL-22 levels were increased in patients with RA compared with controls (mean 432.37 pg/ml and 67.45 pg/ml, respectively; p < 0.001). Levels of IL-22 correlated with DAS28 and CDAI measures. Rheumatoid factor (RF) positivity was correlated with higher levels of IL-22 in patients with RA (mean 575.08 pg/ml; p = 0.001). The presence of bone erosions was associated with high IL-22 levels (p = 0.0001). PBMC stimulated with PMA/ionomycin expressed higher levels of IL-22 in patients with RA than controls but this was not significant (mean 584.75 pg/ml and 295.57 pg/ml; p = 0.553).Conclusion.IL-22 is elevated in the serum of patients with established RA. Elevated serum IL-22 allows discrimination between patients with different clinical and laboratory measures and indicates the potential of IL-22 as an additional tool for assessment of activity in RA, particularly in patients with RF antibodies and longterm disease. IL-22 is associated with bone-destructive disease.

An investigation of the inflammatory cytokine and chemokine network in systemic sclerosis

2011 ◽  
Vol 70 (6) ◽  
pp. 1115-1121 ◽  
Author(s):  
Veronica Codullo ◽  
Helen M Baldwin ◽  
Mark D Singh ◽  
Alasdair R Fraser ◽  
Catherine Wilson ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Mononuclear Cells ◽  
Platelet Rich Plasma ◽  
Critical Role ◽  
Serum Levels ◽  
Pcr Analysis ◽  
Peripheral Blood Mononuclear ◽  
Matrix Deposition ◽  
Disease Subtype ◽  
Inflammatory Chemokines

ObjectivesSystemic sclerosis (SSc) is characterised by vasculopathy, an aberrantly activated immune system and excessive extracellular matrix deposition. Inflammatory chemokines control migration of cells to sites of tissue damage; their removal from inflamed sites is essential for resolution of the inflammatory response. The atypical chemokine receptor D6 has a critical role in this physiological balance. To explore potential deregulation of this system in SSc, inflammatory chemokine and D6 expression were compared with that in healthy controls (HC).MethodsSerum levels of inflammatory mediators were assessed by luminex analysis. Peripheral blood mononuclear cells (PBMCs) were used in molecular and immunocytochemical analysis. Platelet-rich plasma was collected and assessed by western blotting for D6 expression levels. Sex-matched HC were used for comparison.Results72 patients with SSc and 30 HC were enrolled in the study. The chemokines MCP-1/CCL2, MIP-1α/CCL3, MIP-1β/CCL4 and IL-8/CXCL8 were significantly increased in patients with SSc, regardless of disease subtype and phase. Quantitative PCR analysis revealed a significant 10-fold upregulation of D6 transcripts in patients with SSc compared with controls, and this was paralleled by increased D6 protein expression in the PBMCs of patients with SSc. Platelet lysates also showed strong D6 expression in patients with SSc but not in controls. Importantly, high levels of D6 expression correlated with reduced levels of its ligands in serum.ConclusionsInflammatory chemokines and the regulatory receptor D6 are significantly upregulated in SSc and high D6 levels are associated with lower systemic chemokine levels, indicating that some patients control systemic chemokine levels using D6. These results suggest that chemokines may represent a therapeutic target in SSc.

scholarly journals The immunoregulatory function of peripheral blood CD71+ erythroid cells in systemic-onset juvenile idiopathic arthritis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hikaru Kanemasa ◽  
Masataka Ishimura ◽  
Katsuhide Eguchi ◽  
Tamami Tanaka ◽  
Etsuro Nanishi ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Inflammatory Diseases ◽  
Active Phase ◽  
Serum Levels ◽  
Cell Interaction ◽  
Erythroid Cells ◽  
Peripheral Blood Mononuclear ◽  
Systemic Onset

AbstractCD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell–cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2.

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 Talin-1 Gene Expression as a Tumor Marker in Hepatocellular Carcinoma Patients: A Pilot Study

2020 ◽  
Vol 10 (1) ◽  
pp. 15-22 ◽  
Author(s):  
Amal A. Mohamed ◽  
Naglaa El-Toukhy ◽  
Doaa M. Ghaith ◽  
Ingy Badawy ◽  
Sara M. Abdo ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hepatocellular Carcinoma ◽  
Mononuclear Cells ◽  
Tumor Staging ◽  
Serum Levels ◽  
Peripheral Blood Mononuclear ◽  
Primary Liver Tumor ◽  
Staging Systems ◽  
Diagnostic Role ◽  
Serum Alpha Fetoprotein

Background & Aims: Hepatocellular Carcinoma (HCC) is the most common primary liver tumor. It is the second most common cancer in men and the sixth in women in Egypt. One of the proteins participating in the trans-endothelial migration is Talin-1. It also has a role in the formation and metastasis of different types of cancer. This study aimed to evaluate the diagnostic impact of Talin-1 gene expression in HCC Egyptian patients. Methods: Our study included forty HCC patients, thirty liver cirrhosis patients without HCC and thirty healthy subjects. For all groups, clinical and biochemical parameters were investigated. Tumor characteristics were assessed and tumor staging was done using Okuda, CLIP, VISUM and Tokyo staging systems. In addition, Serum Alpha-Fetoprotein (AFP) levels were assayed using Enzyme Immunoassay (EIA) and Talin-1 gene expression was assessed in the Peripheral Blood Mononuclear Cells (PBMCs) via quantitative real-time Polymerase Chain Reaction (PCR). Results: Talin-1 gene expression was significantly upregulated in HCC patients in comparison to cirrhotic and control subjects. The Receiver Operating Characteristic (ROC) analysis indicated that Talin-1 gene expression surpasses serum levels of AFP in the diagnosis of HCC. In particular, the cut off value of 9.5 (2-∆∆Ct) recorded an AUC of 85.7% with a sensitivity of 93.3% and specificity of 80%. Conclusion: Our data confirmed an évident diagnostic role of Talin-1 gene expression for HCC detection.

scholarly journals A New Vision of IgA Nephropathy: The Missing Link

2019 ◽  
Vol 21 (1) ◽  
pp. 189 ◽  
Author(s):  
Fabio Sallustio ◽  
Claudia Curci ◽  
Vincenzo Di Leo ◽  
Anna Gallone ◽  
Francesco Pesce ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Mononuclear Cells ◽  
Serum Levels ◽  
High Serum ◽  
In Vitro Production ◽  
Peripheral Blood Mononuclear ◽  
Familial Form ◽  
New Vision ◽  
New Perspective

IgA Nephropathy (IgAN) is a primary glomerulonephritis problem worldwide that develops mainly in the 2nd and 3rd decade of life and reaches end-stage kidney disease after 20 years from the biopsy-proven diagnosis, implying a great socio-economic burden. IgAN may occur in a sporadic or familial form. Studies on familial IgAN have shown that 66% of asymptomatic relatives carry immunological defects such as high IgA serum levels, abnormal spontaneous in vitro production of IgA from peripheral blood mononuclear cells (PBMCs), high serum levels of aberrantly glycosylated IgA1, and an altered PBMC cytokine production profile. Recent findings led us to focus our attention on a new perspective to study the pathogenesis of this disease, and new studies showed the involvement of factors driven by environment, lifestyle or diet that could affect the disease. In this review, we describe the results of studies carried out in IgAN patients derived from genomic and epigenomic studies. Moreover, we discuss the role of the microbiome in the disease. Finally, we suggest a new vision to consider IgA Nephropathy as a disease that is not disconnected from the environment in which we live but influenced, in addition to the genetic background, also by other environmental and behavioral factors that could be useful for developing precision nephrology and personalized therapy.

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