Chlorogenic Acid (CGA) Isomers Alleviate Interleukin 8 (IL-8) Production in Caco-2 Cells by Decreasing Phosphorylation of p38 and Increasing Cell Integrity

Int J Mol Sci. 2018 Dec 4;19(12):3873. doi: 10.3390/ijms19123873.

Abstract

The objective of this study was to determine the effect of six chlorogenic acid (CGA) isomers known to be present in coffee and other plant foods on modulating the inflammatory response induced by pro-inflammatory cytokines in the Caco-2 human intestinal epithelial cell line. Compared to caffeoylquinic acids (CQA), dicaffeoylquinic acids (DiCQA) had significantly stronger (p < 0.05) capacities to reduce phosphorylation of one of mitogen-activated protein kinases (MAPK) cascades, namely p38. Compared to the control, CQA isomers treatment resulted in around 50% reduction in an interleukin-8 (IL-8) secretion, whereas DiCQA, at the same concentration, resulted in a 90% reduction in IL-8 secretion, compared to the control cells. CGA isomer treatment also showed a significant effect (p < 0.05) on the up-regulation of NFκB subunit p65 nuclear translocation by more than 1.5 times, compared to the control. We concluded that CGA isomers exert anti-inflammatory activity in a mixture of interferon gamma (IFNγ) and phorbol myristate acetate (PMA)-challenged Caco-2 cells, by decreasing the phosphorylation of p38 cascade and up-regulating NFκB signaling.

Keywords: Caco-2 cells; MAPK cascades; NFκB pathway; chlorogenic acid isomers; inflammation.

MeSH terms

  • Caco-2 Cells
  • Chlorogenic Acid / chemistry*
  • Chlorogenic Acid / pharmacology*
  • Electric Impedance
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Humans
  • Interferon-gamma / pharmacology
  • Interleukin-8 / biosynthesis*
  • Isomerism
  • MAP Kinase Signaling System / drug effects
  • NF-kappa B / metabolism
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Time Factors
  • Up-Regulation / drug effects
  • p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

  • Interleukin-8
  • NF-kappa B
  • Chlorogenic Acid
  • Interferon-gamma
  • p38 Mitogen-Activated Protein Kinases
  • Tetradecanoylphorbol Acetate