Leptin activates human B cells to secrete TNF-α, IL-6, and IL-10 via JAK2/STAT3 and p38MAPK/ERK1/2 signaling pathway.
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.
Laboratories of Cellular and Molecular Immunology, Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
Sudhanshu
S
Agrawal
Sastry
S
Gollapudi
Houfen
H
Su
Sudhir
S
Gupta
D015551:Autoimmunity; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D053614:Janus Kinase 2 / Q000032:analysis / Q000096:biosynthesis; D020738:Leptin / Q000494:pharmacology; D008213:Lymphocyte Activation; D048052:Mitogen-Activated Protein Kinase 3 / Q000032:analysis / Q000096:biosynthesis; D048053:Mitogen-Activated Protein Kinase 6 / Q000032:analysis / Q000096:biosynthesis; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000096:biosynthesis; D010766:Phosphorylation / Q000187:drug effects; D054411:Receptors, Leptin / Q000276:immunology / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000032:analysis / Q000096:biosynthesis; D015398:Signal Transduction / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000032:analysis / Q000096:biosynthesis
D015850:Interleukin-6; D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D053614:Janus Kinase 2; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
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