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The molecular events behind ferulic acid mediated modulation of IL-6 expression in LPS-activated Raw 264.7 cells

Immunobiology. 2016 Mar;221(3):486-93. doi: 10.1016/j.imbio.2015.11.001. Epub 2015 Nov 10.

Abstract

Identification of new antioxidant and anti-inflammatory bioactive molecules is an important tool for selecting effective formulations for the treatment of inflammation. The mouse macrophage cell line RAW 264.7, lipopolysaccharide (LPS)-activated, is associated with an inflammation response. Activated macrophages produce reactive oxygen species (ROS), nitric oxide (NO) and inflammatory cytokines such as IL-6, TNF-α and IL-10. In the present study we have showed that pre-treatment with Ferulic Acid (FA) reduces NO accumulation in the culture medium of LPS-induced macrophage cells. Moreover, real-time experiments have revealed that FA has an inhibitory effect at the transcriptional level on the expression of some inflammatory mediators such as IL-6, TNF-α and iNOS and an activation effect on the expression of some antioxidant molecules such as Metallothioneins (MT-1, MT-2). Importantly, we have found that FA reduced the translocation of NF-E2-related factor 2 (Nrf2) and nuclear transcription factor-κB (NF-κB) into the nuclei through a reduction of the expression of phosphorylated IKK and consequently inhibited IL-6 and NF-κB promoter activity in a luciferase assay. Our data clearly suggest that FA anti-inflammatory effects are mainly mediated through IKK/NF-κB signalling pathway. Therefore, FA could represent a new natural drug extremely useful to improve anti-inflammatory treatment.

Keywords: Ferulic Acid; IL-6; LPS; Metallothioneins; NF-κB; NO; Nrf2; ROS; iNOS.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Cell Line
  • Coumaric Acids / pharmacology*
  • Gene Expression
  • Gene Expression Regulation / drug effects*
  • Genes, Reporter
  • I-kappa B Kinase / metabolism
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism*
  • Lipopolysaccharides / immunology
  • Macrophage Activation / drug effects*
  • Macrophage Activation / immunology*
  • Macrophages / drug effects*
  • Macrophages / immunology
  • Macrophages / metabolism*
  • Mice
  • Models, Molecular
  • NF-kappa B / metabolism
  • Nitric Oxide / metabolism
  • Protein Transport
  • Reactive Oxygen Species / metabolism

Substances

  • Antioxidants
  • Coumaric Acids
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Reactive Oxygen Species
  • Nitric Oxide
  • ferulic acid
  • I-kappa B Kinase