Activation of peripheral blood mononuclear cells and leptin secretion: New potential role of interleukin‐2 and high mobility group box (hmgb)1

Andrea Coppola, Barbara Capuani, Francesca Pacifici, Donatella Pastore, Roberto Arriga, Alfonso Bellia, Aikaterini Andreadi, Nicola Di Daniele, Renato Lauro, David Della‐morte, Giuseppe Sconocchia, Davide Lauro

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number7988
JournalInternational journal of molecular sciences
Volume22
Issue number15
DOIs
StatePublished - Aug 1 2021
Externally publishedYes

Keywords

  • HMGB1
  • Leptin
  • Toll‐like receptors system
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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