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PMID: 21243519 Published · ppublish English Journal Article

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

Journal of clinical immunology ·Vol. 31 ·No. 3 ·2011-06-00 ·Pages 472-8

Agrawal S, Gollapudi S, Su H, Gupta S

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,immunology,metabolism Cells, Cultured Dose-Response Relationship, Drug Enzyme-Linked Immunosorbent Assay Humans Inflammation/immunology,metabolism Interleukin-10/analysis,biosynthesis Interleukin-6/analysis,biosynthesis Janus Kinase 2/analysis,biosynthesis Leptin/pharmacology Lymphocyte Activation Mitogen-Activated Protein Kinase 3/analysis,biosynthesis Mitogen-Activated Protein Kinase 6/analysis,biosynthesis Mitogen-Activated Protein Kinases/analysis,biosynthesis Phosphorylation/drug effects Receptors, Leptin/immunology,metabolism STAT3 Transcription Factor/analysis,biosynthesis Signal Transduction/immunology Tumor Necrosis Factor-alpha/analysis,biosynthesis p38 Mitogen-Activated Protein Kinases/analysis,biosynthesis
Chemicals
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
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Agrawal Sudhanshu
Laboratories of Cellular and Molecular Immunology, Division of Basic and Clinical Immunology, University of California, Irvine, CA 92697, USA.
Gollapudi Sastry
Su Houfen
Gupta Sudhir
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Article Info
Journal
Journal of clinical immunology
Abbr.
J Clin Immunol
ISSN
1573-2592
DOI
10.1007/s10875-010-9507-1
Published
2011-06-00
Epub
2011-00-18
Pages
472-8
Language
English
Region
Netherlands
NLM ID
8102137
PMCID
PMC3132280
Subset
IM
External Links
PubMed source DOI: 10.1007/s10875-010-9507-1 PMC Full Text View journal details
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