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