Leptin activates human B cells to secrete TNF-α, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway

J Clin Immunol. 2011 Jun;31(3):472-8. doi: 10.1007/s10875-010-9507-1. Epub 2011 Jan 18.

Abstract

Leptin, one of the adipokines, functions as a hormone and a cytokine. In this investigation, we show for the first time that leptin, in a concentration-dependent manner, activates human peripheral blood B cells to induce secretion of IL-6, IL-10, and TNF-α. Leptin increased B cells expressing CD25 and HLA-DR. Leptin induces phosphorylation of Janus activation kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), p38 mitogen-activated protein kinase (p38MAPK), and extracellular signal-regulated kinase (ERK1/2). Furthermore, leptin-induced cytokine secretion by B cells was blocked by inhibitors of JAK2, STAT3, p38MAPK, and ERK1/2. These data demonstrate that leptin activates human B cells to secrete cytokines via activation of JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathways, which may contribute to its inflammatory and immunoregulatory properties.

MeSH terms

  • Autoimmunity
  • B-Lymphocytes* / drug effects
  • B-Lymphocytes* / immunology
  • B-Lymphocytes* / metabolism
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-10 / analysis
  • Interleukin-10 / biosynthesis
  • Interleukin-6 / analysis
  • Interleukin-6 / biosynthesis
  • Janus Kinase 2 / analysis
  • Janus Kinase 2 / biosynthesis
  • Leptin* / pharmacology
  • Lymphocyte Activation
  • Mitogen-Activated Protein Kinase 3 / analysis
  • Mitogen-Activated Protein Kinase 3 / biosynthesis
  • Mitogen-Activated Protein Kinase 6 / analysis
  • Mitogen-Activated Protein Kinase 6 / biosynthesis
  • Mitogen-Activated Protein Kinases / analysis
  • Mitogen-Activated Protein Kinases / biosynthesis
  • Phosphorylation / drug effects
  • Receptors, Leptin / immunology
  • Receptors, Leptin / metabolism*
  • STAT3 Transcription Factor / analysis
  • STAT3 Transcription Factor / biosynthesis
  • Signal Transduction / immunology*
  • Tumor Necrosis Factor-alpha / analysis
  • Tumor Necrosis Factor-alpha / biosynthesis
  • p38 Mitogen-Activated Protein Kinases / analysis
  • p38 Mitogen-Activated Protein Kinases / biosynthesis

Substances

  • Interleukin-6
  • Leptin
  • Receptors, Leptin
  • STAT3 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Janus Kinase 2
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 6
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases