Olive oil phenolic extract regulates interleukin-8 expression by transcriptional and posttranscriptional mechanisms in Caco-2 cells

Mol Nutr Food Res. 2015 Jun;59(6):1217-21. doi: 10.1002/mnfr.201400800. Epub 2015 Apr 27.

Abstract

In this study, we investigated the ability of a phenolic extract from extra virgin olive oil (OPE) to modulate the inflammatory response in intestinal epithelial cells. Undifferentiated and differentiated Caco-2 cells were challenged with LPS (50 μg/mL) or IL-1β (5 ng/mL) to mimic the early and intermediate phase of intestinal inflammation, respectively. The effects of OPE on nuclear factor-κB-driven transcription and IL-8 promoter activity were evaluated in transfection assays, coupled to p65 nuclear translocation. Modulation of IL-8 mRNA levels by OPE was measured by quantitative RT-PCR while effects on protein levels by ELISA. Specific mitogen activated protein kinases inhibitors were used to investigate mRNA stability and the involvement of related signaling pathways. OPE prevented IL-8 expression and secretion in LPS-treated Caco-2 cells. In the presence of IL-1β OPE exhibited opposing effects on IL-8 gene transcription and mRNA/protein levels. While in IL-1β-treated cells IL-8 promoter activity was inhibited by treatment with OPE, IL-8 mRNA stability was strongly enhanced, leading to increased protein expression. Inhibitors of p38 and extracellular signal-regulated kinases partly prevented OPE effect on IL-8 mRNA levels. Intestinal epithelial cells represent a direct target of the action of olive oil phenols where they regulate IL-8 expression by transcriptional and posttranscriptional mechanisms.

Keywords: Extra-virgin olive oil; IL-8; Inflammation; Intestine; Phenols.

MeSH terms

  • Caco-2 Cells
  • Cell Differentiation / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Extracellular Signal-Regulated MAP Kinases / genetics
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Humans
  • Inflammation / metabolism
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Interleukin-8 / genetics
  • Interleukin-8 / metabolism*
  • Lipopolysaccharides / adverse effects
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Olive Oil / pharmacology*
  • Phenols / pharmacology*
  • Plant Extracts / pharmacology*
  • Promoter Regions, Genetic
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction
  • Transcriptional Activation*

Substances

  • CXCL8 protein, human
  • Interleukin-1beta
  • Interleukin-8
  • Lipopolysaccharides
  • NF-kappa B
  • Olive Oil
  • Phenols
  • Plant Extracts
  • RNA, Messenger
  • Extracellular Signal-Regulated MAP Kinases