Adiponectin inhibits pro-inflammatory signaling in human macrophages independent of interleukin-10

J Biol Chem. 2009 Sep 18;284(38):25569-75. doi: 10.1074/jbc.M109.019786. Epub 2009 Jul 18.


Macrophages participate pivotally in the pathogenesis of many chronic inflammatory diseases including atherosclerosis. Adiponectin, a vasculoprotective molecule with insulin-sensitizing and anti-atherogenic properties, suppresses pro-inflammatory gene expression in macrophages by mechanisms that remain incompletely understood. This study investigated the effects of adiponectin on major pro-inflammatory signaling pathways in human macrophages. We demonstrate that pretreatment of these cells with adiponectin inhibits phosphorylation of nuclear factor kappaB inhibitor (IkappaB), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK), induced by either lipopolysaccharide (LPS) or tumor necrosis factor (TNF) alpha, as well as STAT3 phosphorylation induced by interleukin-6 (IL6). Antagonism of IL10 by either neutralizing antibodies or siRNA-mediated silencing did not abrogate the anti-inflammatory actions of adiponectin, indicating that the ability of adiponectin to render human macrophages tolerant to various pro-inflammatory stimuli does not require this cytokine. A systematic search for adiponectin-inducible genes with established anti-inflammatory properties revealed that adiponectin augmented the expression of A20, suppressor of cytokine signaling (SOCS) 3, B-cell CLL/lymphoma (BCL) 3, TNF receptor-associated factor (TRAF) 1, and TNFAIP3-interacting protein (TNIP) 3. These results suggest that adiponectin triggers a multifaceted response in human macrophages by inducing the expression of various anti-inflammatory proteins that act at different levels in concert to suppress macrophage activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiponectin / metabolism
  • Adiponectin / pharmacology
  • B-Cell Lymphoma 3 Protein
  • Cell Line
  • DNA-Binding Proteins
  • Gene Expression Regulation / drug effects
  • Humans
  • I-kappa B Proteins / metabolism
  • Inflammation / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-10 / pharmacology*
  • Interleukin-6 / metabolism
  • Interleukin-6 / pharmacology
  • Intracellular Signaling Peptides and Proteins
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / pharmacology
  • MAP Kinase Signaling System / drug effects*
  • Macrophages / metabolism*
  • Nuclear Proteins / biosynthesis
  • Phosphorylation / drug effects
  • Proteins / metabolism
  • Proto-Oncogene Proteins / biosynthesis
  • STAT3 Transcription Factor / biosynthesis
  • TNF Receptor-Associated Factor 1 / biosynthesis
  • Transcription Factors / biosynthesis
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Tumor Necrosis Factor-alpha / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • ADIPOQ protein, human
  • Adiponectin
  • B-Cell Lymphoma 3 Protein
  • BCL3 protein, human
  • DNA-Binding Proteins
  • I-kappa B Proteins
  • IL10 protein, human
  • IL6 protein, human
  • Interleukin-6
  • Intracellular Signaling Peptides and Proteins
  • Lipopolysaccharides
  • Nuclear Proteins
  • Proteins
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • TNF Receptor-Associated Factor 1
  • TNIP3 protein, human
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3