Activation of Peripheral Blood Mononuclear Cells and Leptin Secretion: New Potential Role of Interleukin-2 and High Mobility Group Box (HMGB)1

• Published in: International journal of molecular sciences 2021-08, Vol.22 (15), p.7988
• Main Authors: Coppola, Andrea, Capuani, Barbara, Pacifici, Francesca, Pastore, Donatella, Arriga, Roberto, Bellia, Alfonso, Andreadi, Aikaterini, Di Daniele, Nicola, Lauro, Renato, Della-Morte, David, Sconocchia, Giuseppe, Lauro, Davide
• Format: Article
• Language: English
• Subjects: Blood; Cardiovascular disease; Chronic illnesses; Cytokines; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Glucose; Heart failure; HMGB1; HMGB1 protein; Hyperglycemia; Hyperinsulinemia; IL-1β; Immunoglobulin A; Inflammation; Inflammatory response; Innate immunity; Insulin resistance; Interleukin 2; Leptin; Leukocytes (mononuclear); Ligands; Lymphocytes; Metabolic disorders; Mobility; Monocytes; Pathogenesis; Patients; Peripheral blood mononuclear cells; TLR2 protein; TLR4 protein; Toll-like receptors; toll-like receptors system; Tumor necrosis factor-TNF; type 2 diabetes mellitus
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms22157988

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.