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The inflammatory state of adipose tissue is not affected by the anti-inflammatory response of the A2a-adenosine system and miR-221/PTEN

Cortés-Garcia, J.D., Briones-Espinoza, M.J., Vega-Cárdenas, M., Ruíz-Rodríguez, V.M., Mendez-Mancilla, A., Gómez-Otero, Arturo E., Vargas Morales, J.M., García-Hernández, M.H., Portales-Pérez, D.P.
The international journal of biochemistry & cell biology 2018 v.100 pp. 42-48
adipokines, adipose tissue, blood, body mass index, carcinogenesis, cell proliferation, collagenase, cytokines, ficoll, flow cytometry, immunomodulators, inflammation, microRNA, obesity, patients, quantitative polymerase chain reaction, reverse transcriptase polymerase chain reaction
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/m² (BMI < 25) and BMI ≥ 25 kg/m² (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+, 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.