Naringin inhibits chemokine production in an LPS-induced RAW 264.7 macrophage cell line

Mol Med Rep. 2012 Dec;6(6):1343-50. doi: 10.3892/mmr.2012.1072. Epub 2012 Sep 10.

Abstract

Naringin has been reported to act as an effective anti-inflammatory compound. In a previous study, we demonstrated that the anti-inflammatory effect of naringin on lipopolysaccharide (LPS)-induced acute lung injury in mice correlated with the inhibition of the nuclear factor-κB (NF-κB) pathway. However, the effects and mechanism of action of naringin on LPS-induced chemokine expression are not yet fully understood. This study aimed to evaluate the effect of naringin on chemokine expression in LPS-induced RAW 264.7 macrophages and to provide insights into the possible underlying mechanisms. We found that the in vitro pre-treatment with naringin led to a significant attenuation in the LPS-induced secretion of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α). RT-qPCR demonstrated that naringin significantly reduced the LPS-induced upregulation of IL-8, MCP-1 and MIP-1α mRNA expression in a dose-dependent manner. Additionally, western blot analysis revealed that naringin effectively suppressed NF-κB activation by inhibiting the degradation of IκB-α and the translocation of p65. Naringin also attenuated MAPK activation by inhibiting the phosphorylation of ERK1/2, JNK and p38 MAPK. Taken together, these demonstrate that naringin reduces IL-8, MCP-1 and MIP-1α secretion and mRNA expression, possibly by blocking the activation of the NF-κB and MAPK signaling pathways in LPS-induced RAW 264.7 macrophages.

Keywords: naringin; lipopolysaccharide; interleukin-8; monocyte chemoattractant protein-1; macrophage inflammatory protein-1α; nuclear factor-κB; mitogen-activated protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Flavanones / pharmacology*
  • Gene Expression / drug effects*
  • I-kappa B Proteins / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / toxicity
  • Macrophages / drug effects
  • Mice
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • RNA, Messenger / metabolism
  • Receptors, CCR2 / genetics
  • Receptors, CCR2 / metabolism
  • Signal Transduction / drug effects
  • Transcription Factor RelA / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Chemokine CCL3
  • Chemokines
  • Flavanones
  • I-kappa B Proteins
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • Nfkbia protein, mouse
  • RNA, Messenger
  • Receptors, CCR2
  • Transcription Factor RelA
  • NF-KappaB Inhibitor alpha
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • p38 Mitogen-Activated Protein Kinases
  • naringin