Quercetin suppresses MIP-1α-induced adipose inflammation by downregulating its receptors CCR1/CCR5 and inhibiting inflammatory signaling

J Med Food. 2014 May;17(5):550-7. doi: 10.1089/jmf.2013.2912. Epub 2013 Dec 10.

Abstract

Obesity-induced inflammation is characterized by recruitment of adipose tissue macrophages that release inflammatory cytokines and chemokines. MIP-1α (macrophage inflammatory protein 1α)/CCL3, a CC chemokine, induces monocyte/macrophage infiltration and thus is implicated in obesity-induced adipose inflammation. Quercetin has been shown to modulate obesity-induced inflammation, but the mechanism of its action remains unclear. Here we demonstrate that quercetin decreases MIP-1α release from adipocytes and macrophages and from cocultured adipocytes/macrophages; it also opposes MIP-1α-induced macrophage infiltration and activation. The inhibitory action of quercetin on the MIP-1α-induced inflammatory responses of macrophages is mediated by downregulation of CCR1/CCR5, and inhibition of activation of JNK, p38 mitogen-activated-protein kinase (MAPK), and IKK as well as IκBα degradation. These findings suggest that quercetin may be a useful agent against obesity-induced adipose tissue inflammation.

Keywords: adipose tissue; chemokine; inflammation; obesity; quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / metabolism
  • Adipose Tissue* / chemistry
  • Animals
  • Cell Line
  • Chemokine CCL3 / antagonists & inhibitors*
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / physiology
  • Chemotaxis / drug effects
  • Coculture Techniques
  • Culture Media, Conditioned
  • Down-Regulation / drug effects
  • Enzyme Activation / drug effects
  • Inflammation / etiology
  • Inflammation / prevention & control*
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • Obesity / complications
  • Quercetin / pharmacology*
  • RNA, Messenger / analysis
  • Receptors, CCR / genetics*
  • Receptors, CCR1 / genetics
  • Receptors, CCR5 / genetics
  • Signal Transduction / drug effects
  • p38 Mitogen-Activated Protein Kinases

Substances

  • Chemokine CCL3
  • Culture Media, Conditioned
  • RNA, Messenger
  • Receptors, CCR
  • Receptors, CCR1
  • Receptors, CCR5
  • Quercetin
  • Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases