Atorvastatin Inhibited ROS Generation and Increased IL-1β And IL-6 Release by Mononuclear Cells from Diabetic Patients

2019 ◽  
Vol 19 (8) ◽  
pp. 1207-1215
Author(s):  
Paula M.F. dos Anjos ◽  
Caroline M.O. Volpe ◽  
Thaís C. Miranda ◽  
José A. Nogueira-Machado
Keyword(s):  
Nadph Oxidase ◽  
Mononuclear Cells ◽  
Cytokine Secretion ◽  
Ros Generation ◽  
Diabetic Patients ◽  
Peripheral Blood Mononuclear ◽  
Mitochondrial Ros ◽  
Healthy Control ◽  
Cholesterol Fraction

Background: Atorvastatin (ATV) inhibits the conversion of 3-Hydroxy-3-Methylglutaryl Coenzyme A (HMG-CoA) to mevalonate formation and promotes lowering of the LDL cholesterol fraction. However, ATV exhibits pleiotropic metabolic actions beyond cholesterol-lowering properties. Objective: We aimed to evaluate the effect of ATV on oxidizing species generation and cytokine secretion in Peripheral Blood Mononuclear Cells (PBMNC) of Type 2 Diabetes Mellitus (T2DM) patients in comparison to healthy control. Methods: Both NADPH-oxidase-dependent and mitochondrial ROS generation were assessed by chemoluminescence luminol-dependent assay and fluorometric experiment, using Dichlorofluorescein Assay (DCFH-DA), respectively. IL-1β and IL-6 were quantified by classical ELISA. Results: ATV inhibited NADPH-oxidase dependent ROS generation, but showed no effect on mitochondrial ROS generation and activated IL-1β and IL-6 secretions in PBMNC from control and T2DM patients. ROS generation and cytokine secretion in the presence of an inhibitor of Protein Kinase Cβ (iPKCβ) and ATV led to similar results. The secretion of IL-1β, PDB-induced in the presence of iPKCβ, but not ATV, was increased. ATV and iPKCβ exacerbated PDB-induced IL-6 secretion. LPS activated the secretion of IL-1β and IL-6 which was potentiated by ATV. Conclusion: ATV inhibited ROS generation and activated IL-1 β/IL-6 secretion in PBMNC of diabetes patients. Its effect was not affected by the hyperglymemia.

scholarly journals Diabetes potentiates ROS production in granulocytes from patients with chronic kidney disease

2021 ◽  
Vol 9 (1) ◽  
pp. 9-14
Author(s):  
Jose Augusto Nogueira-Machado ◽  
Gabriela Rossi Ferreira ◽  
Caroline Maria Oliveira Volpe ◽  
Pedro Henrique Villar-Delfino ◽  
Fabiana Rocha Silva
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Nadph Oxidase ◽  
Ros Generation ◽  
Ros Production ◽  
Clinical Prognosis ◽  
Before And After ◽  
Healthy Control ◽  
Toll Receptor

Background: Type 2 diabetes (DM2) and chronic kidney disease (CKD) are inflammatory pathologies. Diabetes is characterized by hyperglycemia and CKD by the gradual and irreversible loss of kidney function. Both diseases develop oxidative stress, and reactive oxygen species (ROS) play a pivotal role in the pathogenesis. This study aimed to determine ROS production by granulocytes from renal patients (CKD) with or without diabetes. Methods: Granulocytes from patients with DM2, CKD, CKD-DM2, and healthy controls were purified using the Ficoll-Hypaque gradient method. Granulocyte ROS generation in the absence or the presence of PDB (an activator of NADPH-oxidase) or Concanavalin A (Toll- receptor 3,9 activator) was evaluated in a luminol-dependent chemiluminescence method. The cell-free DNA in the serum of DM2, CKD, and CKD-DM2 patients was measured by the fluorescence method before and after hemodialysis. Results: Our results show a significant increase in ROS production by granulocytes from patients with CKD, DM2, and CKD-DM2 compared to healthy control (p<0.05). CKD-DM2 group produced the most significant ROS levels with or without NADPH-oxidase activation. ROS production showed a significant increase in the presence of ConA. In contrast, mitochondrial (internal) ROS showed a different ROS response. DNA extrusion was higher in the CKD-DM2 group after hemodialysis suggesting cell death. Conclusion: The results demonstrated that CKD-DM2 patients produced high ROS generation levels and increased DNA extrusion after hemodialysis. It may suggest that CKD-DM2 disease is more severe and has a worse clinical prognosis.

scholarly journals miR-145 improves metabolic inflammatory disease through multiple pathways

2019 ◽  
Vol 12 (2) ◽  
pp. 152-162 ◽  
Author(s):  
Min He ◽  
Nan Wu ◽  
Man Cheong Leong ◽  
Weiwei Zhang ◽  
Zi Ye ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Therapeutic Strategy ◽  
Mononuclear Cells ◽  
Metabolic Diseases ◽  
Diabetic Patients ◽  
Peripheral Blood Mononuclear ◽  
Reduced Body ◽  
Type 2 Diabetics ◽  
Induced Apoptosis

Abstract Chronic inflammation plays a pivotal role in insulin resistance and type 2 diabetes, yet the mechanisms are not completely understood. Here, we demonstrated that serum LPS levels were significantly higher in newly diagnosed diabetic patients than in normal control. miR-145 level in peripheral blood mononuclear cells decreased in type 2 diabetics. LPS repressed the transcription of miR-143/145 cluster and decreased miR-145 levels. Attenuation of miR-145 activity by anti-miR-145 triggered liver inflammation and increased serum chemokines in C57BL/6 J mice. Conversely, lentivirus-mediated miR-145 overexpression inhibited macrophage infiltration, reduced body weight, and improved glucose metabolism in db/db mice. And miR-145 overexpression markedly reduced plaque size in the aorta in ApoE−/− mice. Both OPG and KLF5 were targets of miR-145. miR-145 repressed cell proliferation and induced apoptosis partially by targeting OPG and KLF5. miR-145 also suppressed NF-κB activation by targeting OPG and KLF5. Our findings provide an association of the environment with the progress of metabolic disorders. Increasing miR-145 may be a new potential therapeutic strategy in preventing and treating metabolic diseases such as type 2 diabetes and atherosclerosis.

scholarly journals Effect of metabolic control on the in vitro proliferation of peripheral blood mononuclear cells in type 1 and type 2 diabetic patients

2006 ◽  
Vol 124 (4) ◽  
pp. 219-222 ◽  
Author(s):  
Maria Cristina Foss-Freitas ◽  
Norma Tiraboschi Foss ◽  
Eduardo Antonio Donadi ◽  
Milton Cesar Foss
Keyword(s):  
Metabolic Control ◽  
Mononuclear Cells ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
In Vitro Proliferation ◽  
Peripheral Blood Mononuclear ◽  
Type 2 Diabetic

CONTEXT AND OBJECTIVE: Diabetes mellitus is a clinical syndrome that frequently leads to the development of chronic complications and high susceptibility to infections. It is probably due to defective immunological defense, which may be related to metabolic control of the disease. The aim of this study was to evaluate the effect of metabolic control on immune-cell behavior in type 1 and type 2 diabetic patients. For this, the in vitro proliferation of peripheral blood mononuclear cells (PBMC) was analyzed in patients with inadequate and adequate metabolic control. DESIGN AND SETTING: Experimental/laboratory study at a university hospital. METHODS: Eleven type 1 and thirteen type 2 diabetic patients were studied, together with 21 healthy individuals divided in two groups (11/10), who were matched by sex and age with those diabetic patients. PBMC cultures stimulated with concanavalin-A (Con-A) were used to measure ³H-thymidine incorporation after 72 hours of cell culturing. For patients with inadequate metabolic control, culturing was performed on the first day of patient hospitalization and again after intensive treatment to achieve adequate control. RESULTS: The proliferation index for Con-A-stimulated cultures from type 1 diabetic patients was significantly greater than that for cultures from healthy individuals and type 2 diabetic patients, independent of metabolic control. A negative correlation between the proliferation cell index and body mass index and serum C-reactive protein levels was also observed. CONCLUSION: The increase in the proliferation capacity of type 1 diabetic T lymphocytes was probably not caused by hyperglycemia and/or insulinopenia related to inadequate metabolic control.

scholarly journals Expression and Significance of MMPs in Synovial Fluid, Serum and PBMC Culture Supernatant Stimulated by LPS in Osteoarthritis Patients With or Without Diabetes

2017 ◽  
Vol 127 (04) ◽  
pp. 195-202 ◽  
Author(s):  
Simin Luo ◽  
Qiping Shi ◽  
Junyuan Chen ◽  
Huajun Wang ◽  
Wenrui Wu ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Mononuclear Cells ◽  
Culture Supernatant ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peripheral Blood Mononuclear ◽  
Pbmc Culture ◽  
Knee Oa ◽  
Healthy Control ◽  
And Function

Abstract Objective Patients with Type 2 Diabetes mellitus (T2DM) are prone to osteoarthritis (OA). Matrix metalloproteinases (MMPs), an essential modulator in cartilage matrix homeostasis, increase in T2DM and OA. We aimed to ascertain the expression difference of MMPs and function in mononuclear cells after stimulating by lipopolysaccharide (LPS) in OA patients with or without diabetes. Methods 30 knee OA patients without T2DM (OA group), 20 knee OA patients with T2DM (DM-OA group) and 5 healthy volunteers recruited as control were enrolled from January 2016 to January 2017. The expression levels of MMPs in both serum and synovial fluid were initially detected in three groups by enzyme-linked immunosorbent assay (ELISA). After stimulation of peripheral blood mononuclear cell (PBMC) with LPS, the release of MMPs were determined and evaluated. Results The expression of MMP-1, -7, -8, -9, -10 and -12 in synovial fluid in DM-OA group were significantly higher than in OA group and healthy control. The expression of MMP-1 and -7 in serum were highest in DM-OA group. LPS significantly promotes the production of MMP-1, -8, -9 and -10 in PBMC of each group after 4 h stimulation. It is worth to note that the LPS-stimulated MMP-8 and -9 elevations were more prominent in DM-OA group compared with their counterparts. Conclusion High levels of MMP-1, -7, -8, -9, -10, and -12 in the synovial fluid might be one of important reasons that diabetes patients are more frequently suffered from OA. Inflammation-induced malfunction of mononuclear cells would stimulate MMP-8 and -9 secretion to various extents.

scholarly journals CD30-mediated signaling promotes the development of human T helper type 2-like T cells.

1995 ◽  
Vol 182 (6) ◽  
pp. 1655-1661 ◽  
Author(s):  
G Del Prete ◽  
M De Carli ◽  
M M D'Elios ◽  
K C Daniel ◽  
F Almerigogna ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
T Cells ◽  
T Cell ◽  
Mononuclear Cells ◽  
Growth Factor Receptor ◽  
Cytokine Secretion ◽  
T Helper ◽  
Peripheral Blood Mononuclear ◽  
Human T Cell

We have recently shown that CD30, a member of the tumor necrosis factor/nerve growth factor receptor superfamily, is preferentially expressed by human T cell clones producing T helper (Th) type 2 cytokines. We report here that costimulation with an agonistic anti-CD30 monoclonal antibody enhanced antigen (Ag)-induced proliferation and cytokine secretion by established human Th2 and Th0 clones. Moreover, costimulation of peripheral blood mononuclear cells with the same anti-CD30 monoclonal antibody resulted in the preferential development of Ag-specific T cell lines and clones showing a Th2-like profile of cytokine secretion. In contrast, early blockade in bulk culture of CD30 ligand-CD30 interaction shifted the development of Ag-specific T cells towards the opposite (Th1-like) phenotype. Taken together, these data suggest that CD30 triggering of activated Th cells by CD30 ligand-expressing Ag-presenting cells may represent an important costimulatory signaling for the development of Th2-type responses.

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