Pro-inflammatory NF-κB and early growth response gene 1 regulate epithelial barrier disruption by food additive carrageenan in human intestinal epithelial cells

Toxicol Lett. 2012 Jun 20;211(3):289-95. doi: 10.1016/j.toxlet.2012.04.012. Epub 2012 Apr 26.


The widely used food additive carrageenan (CGN) has been shown to induce intestinal inflammation, ulcerative colitis-like symptoms, or neoplasm in the gut epithelia in animal models, which are also clinical features of human inflammatory bowel disease. In this study, the effects of CGN on pro-inflammatory transcription factors NF-κB and early growth response gene 1 product (EGR-1) were evaluated in terms of human intestinal epithelial barrier integrity. Both pro-inflammatory transcription factors were elevated by CGN and only NF-κB activation was shown to be involved in the induction of pro-inflammatory cytokine interleukin-8. Moreover, the integrity of the in vitro epithelial monolayer under the CGN insult was maintained by both activated pro-inflammatory transcription factors NF-κB and EGR-1. Suppression of NF-κB or EGR-1 aggravated barrier disruption by CGN, which was associated with the reduced gene expression of tight junction component zonula occludens 1 and its irregular localization in the epithelial monolayer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Caco-2 Cells
  • Carcinogens / toxicity*
  • Carrageenan / toxicity*
  • Cell Line
  • Early Growth Response Protein 1 / physiology*
  • Electric Impedance
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism*
  • Food Additives / toxicity*
  • Gene Expression / drug effects
  • HT29 Cells
  • Humans
  • Interleukin-8 / biosynthesis
  • Intestinal Absorption / physiology
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / metabolism*
  • Microscopy, Confocal
  • NF-kappa B / physiology*
  • Plasmids / genetics
  • Real-Time Polymerase Chain Reaction
  • Transfection


  • Carcinogens
  • EGR1 protein, human
  • Early Growth Response Protein 1
  • Food Additives
  • Interleukin-8
  • NF-kappa B
  • Carrageenan