scholarly journals Downregulation of miR-342-3p/miR-342-5p in type 1 diabetes mellitus and vascular health; Case controlled study in peripheral blood mononuclear cells and plasma, CD45dimCD34+CD133+ cells, inflammatory markers, CXCR1/2 and PANEX2 mRNA combined with Ingenuity Pathway Analysis

2020 ◽  
Author(s):  
Sabina L Ray ◽  
David J Coulson ◽  
Megan LY Yeoh ◽  
Sherin Bakhashab ◽  
Alice Tamara ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Inflammatory Cytokines ◽  
Pathway Analysis ◽  
Inflammatory Markers ◽  
Mononuclear Cells ◽  
Vascular Health ◽  
Peripheral Blood Mononuclear ◽  
Tnf Α ◽  
Blood Mononuclear Cells

Abstract BACKGROUND Cardiovascular disease (CVD), the leading causes of death worldwide, correlates with inflammation and shortens life span in type 1 diabetes (T1DM). In animals, miR-342 were shown to be anti-inflammatory in CVD. We hypothesise: proangiogenic miR-342-3p/-5p are downregulated in T1DM whereas inflammatory cytokines are upregulated.METHODS We studied plasma/peripheral blood mononuclear cells (PBMCs) in 29 T1DM and 20 controls (HC). Vascular health was measured by Fibronectin Adhesion Assay (FAA), CD45 dim CD34 + 133 + cells (flow cytometry) and Tissue inhibitor of metalloproteases (TIMP-1). Inflammatory markers IL-7, IL-8, TNFα and VEGF-C were assayed by Mesoscale assay, mRNA for chemokine receptor CXCR1/2, PANX2 and miR 342-3p/5p by qRT-PCR. Analysis: Unpaired Student t test, Pearson correlation and Ingenuity Pathway Analysis (IPA) to predict miR-342-3p/-5p targets.RESULTS In T1DM, pro-inflammatory cytokines IL-8 and TNF-α, IL-7 and growth factor VEGF-C were increased versus HCs; p=0.008, p=0.003, p=0.041 and p=0.013 respectively. MiR-342-3p/-5p were downregulated in PBMCs in T1DM versus HC; p=0.01, but not in plasma. PANX2, CXCR1 and CXCR2 mRNA were increased in PBMCs in T1DM versus HCs; p=0.004, p=0.017 and p<0.001 respectively. MiR-342-3p correlated negatively with TIMP-1, IL-6, IL-8, TNF-α, HbA 1c ; p=0.006, p=0.031, p=0.029, p=0.038, p=0.001, p=0.031 whilst miR-342-5p with TIMP-1, IL-6, IL-8, HbA 1c , p=0.005, p=0.034, p=0.029, p=0.001, p=0.042 respectively. There was positive correlation between miR-342-3p and FAA, CXCR1, CXCR2; p=0.006, p=0.019, p=0.001 and between miR-342 - 5p and FAA, CXCR2; p=0.038, p=0.036 respectively. IPA predicted miR-342-3p/-5p to be anti-inflammatory through the indirect regulation of mitogen-activated protein 3 kinase 1, inhibitor of nuclear factor kappa B kinase regulatory subunit Gamma, Surfactant protein A1 and PANX2 as well as predicting IL-8, TNF-α, IL-7 and glucose to activate the inflammatory response. ROC curve analyses showed: miR-342-3p/-5p to be a biomarker for T1DM: p=0.01, p =0.006 respectively (2) significant downregulation of miR-342-3p/-5p has occured at HbA 1c > 46.45 mmol/mol, p=0.006, p =0.005 respectively.CONCLUSION Our findings validated animal studies. Downregulation of miR-342-3p/-5p by hyperglycaemia and increase in cytokines confirmed inflammation in T1DM. MiR-342-3p/5p correlated with indices of vascular health and defined early CVD at HbA1c of 46.5 mmol/mol cut off point. MiR-342-3p/-5p based either intervention or monitoring may prove to be beneficial in CVD in T1DM.

scholarly journals Type 1 diabetes alters lipid handling and metabolism in human fibroblasts and peripheral blood mononuclear cells

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0188474 ◽  
Author(s):  
Albert R. Jones IV ◽  
Emily L. Coleman ◽  
Nicholas R. Husni ◽  
Jude T. Deeney ◽  
Forum Raval ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Fibroblasts ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Low bone mineral density in patients with type 1 diabetes: association with reduced expression ofIGF1,IGF1RandTGF B 1in peripheral blood mononuclear cells

2016 ◽  
Vol 32 (6) ◽  
pp. 589-595 ◽  
Author(s):  
Karla Simone Costa de Souza ◽  
Marcela Abbott Galvão Ururahy ◽  
Yonara Monique da Costa Oliveira ◽  
Melina Bezerra Loureiro ◽  
Heglayne Pereira Vital da Silva ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Type 1 Diabetes ◽  
Bone Mineral ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Mineral Density ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals Dihydroxylated phenolic acids derived from microbial metabolism reduce lipopolysaccharide-stimulated cytokine secretion by human peripheral blood mononuclear cells

2009 ◽  
Vol 102 (2) ◽  
pp. 201-206 ◽  
Author(s):  
María Monagas ◽  
Nasiruddin Khan ◽  
Cristina Andrés-Lacueva ◽  
Mireia Urpí-Sardá ◽  
Mónica Vázquez-Agell ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Phenolic Acids ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Phenolic Metabolites ◽  
Tnf Α ◽  
Blood Mononuclear Cells ◽  
Pro Inflammatory Cytokines

Oligomers and polymers of flavan-3-ols (proanthocyanidins) are very abundant in the Mediterranean diet, but are poorly absorbed. However, when these polyphenols reach the colon, they are metabolised by the intestinal microbiota into various phenolic acids, including phenylpropionic, phenylacetic and benzoic acid derivatives. Since the biological properties of these metabolites are not completely known, in the present study, we investigated the effect of the following microbial phenolic metabolites: 3,4-dihydroxyphenylpropionic acid (3,4-DHPPA), 3-hydroxyphenylpropionic acid, 3,4-dihydroxyphenylacetic acid (3,4-DHPAA), 3-hydroxyphenylacetic acid, 4-hydroxybenzoic acid and 4-hydroxyhippuric acid (4-HHA), on modulation of the production of the main pro-inflammatory cytokines (TNF-α, IL-1β and IL-6). The production of these cytokines by lipopolysaccharide (LPS)-stimulated peripheral blood mononuclear cells (PBMC) pre-treated with the phenolic metabolites was studied in six healthy volunteers. With the exception of 4-HHA for TNF-α secretion, only the dihydroxylated compounds, 3,4-DHPPA and 3,4-DHPAA, significantly inhibited the secretion of these pro-inflammatory cytokines in LPS-stimulated PBMC. Mean inhibition of the secretion of TNF-α by 3,4-DHPPA and 3,4-DHPAA was 84·9 and 86·4 %, respectively. The concentrations of IL-6 in the culture supernatant were reduced by 88·8 and 92·3 % with 3,4-DHPPA and 3,4-DHPAA pre-treatment, respectively. Finally, inhibition was slightly higher for IL-1β, 93·1 % by 3,4-DHPPA and 97·9 % by 3,4-DHPAA. These results indicate that dihydroxylated phenolic acids derived from microbial metabolism present marked anti-inflammatory properties, providing additional information about the health benefits of dietary polyphenols and their potential value as therapeutic agents.

scholarly journals Circulating and cell-bound antibodies increase coxsackievirus B4-induced production of IFN-α by peripheral blood mononuclear cells from patients with type 1 diabetes

2002 ◽  
Vol 83 (9) ◽  
pp. 2169-2176 ◽  
Author(s):  
Didier Hober ◽  
Wassim Chehadeh ◽  
Jacques Weill ◽  
Christine Hober ◽  
Marie-Christine Vantyghem ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Coxsackievirus B4 ◽  
Blood Mononuclear Cells

Increased levels of IFN-α have been found in patients with type 1 diabetes who have detectable levels of coxsackievirus B4 (CVB4) RNA in their blood. The IFN-α-inducing activity of CVB4 in vitro is weak but can be enhanced by human IgGs. Therefore, it was investigated in vitro whether a preferential IFN-α response of peripheral blood mononuclear cells (PBMCs) to CVB4 exists in patients with type 1 diabetes (n=56) compared with healthy subjects (n=20) and whether antibodies play a role. In patients, the levels of IFN-α obtained after stimulation by PBMCs with CVB4 were higher (P=0·008), an individual IFN-α response by PBMCs to CVB4 was more frequent (P=0·0004) and increased levels of IFN-α were observed in CVB4-infected whole blood cultures. The IFN-α-inducing activity of patients plasma and IgGs mixed with CVB4 and then added to PBMCs was high in comparison with healthy subjects (P<0·001) and was inhibited by preincubating the cells with anti-FcγRII, anti-FcγRIII and anti-CAR (coxsackievirus and adenovirus receptor) antibodies. The strong IFN-α responsiveness of PBMCs to CVB4 suggested that IgGs bound to the cell surface might play a role. A short 56 °C incubation of PBMCs from patients responsive to CVB4 generated supernatants, which, when added to cells, exhibited IFN-α-enhancing activity in combination with CVB4, whereas those of controls did not. Specific antibodies for FcγRI, FcγRII and CAR inhibited this activity. These studies demonstrate that CVB4, through interactions with circulating and/or cell-bound IgGs, can strongly induce the production of IFN-α by PBMCs from patients with type 1 diabetes.

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