The inflammatory state of adipose tissue is not affected by the anti-inflammatory response of the A2a-adenosine system and miR-221/PTEN
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Obesity is a chronic inflammatory state with cytokines, adipokines, and miRNAs. The A2a-adenosine system decreases activation and cytokine release in immune cells. MiR-221 is upregulated in carcinogenesis and inflammatory processes, where its targets PTEN and ETS-1, negatively regulates the Akt pathway and induces the release of pro-inflammatory cytokines, respectively. However, the roles of the A2a-adenosine system and miR-221 in adipose tissue are unknown. The aim of this work was to evaluate the A2a-adenosine and miRNA pathways as immune modulators in adipose tissue. We collected aspirate of adipose tissue from patients with BMI < 25 kg/m 2 (BMI < 25) and BMI ≥ 25 kg/m 2 (BMI ≥ 25) who underwent liposuction; the adipose tissue was digested with collagenase, and then a Ficoll gradient was performed to obtain mononuclear cells from adipose tissue (MCAT). We evaluated the A2a levels by quantitative Retro-transcriptase Polymerase Chain Reaction (RT-qPCR) and flow cytometry and the A2a-adenosine function with a proliferation assay or cytokine levels in the presence or absence of NAD%2b, activators, and inhibitors of the system. We also analyzed miR-221, ETS-1 and PTEN levels by qRT-PCR. First, we detected that MCAT presented higher basal proliferation than mononuclear cells from peripheral blood; however, activation of the A2a receptor downregulated cell proliferation and cytokine release. Interestingly, while miR-221 was downregulated in MCAT from subjects with BMI ≥ 25 compared to BMI < 25, their targets ETS-1 and PTEN, were increased. In conclusion, the A2a-adenosine system is decreased in MCAT, but it maintains its function; moreover, miR-221 could participate in promoting inflammation in adipose tissue. © 2018 Elsevier Ltd
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A2a receptor; Adipose tissue and obesity; Inflammation; miR-221 adenosine A1 receptor; adenosine A2a receptor; adenosine A2b receptor; adenosine A3 receptor; gamma interferon; interleukin 10; interleukin 17; interleukin 1beta; interleukin 2; interleukin 6; microRNA; microRNA 221; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; transcription factor Ets 1; tumor necrosis factor; adenosine A2a receptor; microRNA; MIRN221 microRNA, human; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; PTEN protein, human; adipose tissue; Article; body mass; cell proliferation; controlled study; cytokine release; female; human; human cell; inflammation; liposuction; male; mononuclear cell; obesity; peripheral blood mononuclear cell; adipose tissue; adult; gene expression regulation; genetics; inflammation; metabolism; pathology; Adipose Tissue; Adult; Female; Gene Expression Regulation; Humans; Inflammation; Male; MicroRNAs; PTEN Phosphohydrolase; Receptor, Adenosine A2A
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