κ-carrageenan induces the disruption of intestinal epithelial Caco-2 monolayers by promoting the interaction between intestinal epithelial cells and immune cells

Mol Med Rep. 2013 Dec;8(6):1635-42. doi: 10.3892/mmr.2013.1726. Epub 2013 Oct 14.

Abstract

κ-carrageenan (κ-CGN) is an important food additive that has been demonstrated to induce colitis in animal models. In the present study, the effects of κ-CGN were assessed using an in vitro co-culture system that contained intestinal epithelial Caco-2 cells and activated macrophage-like THP-1 cells. The results demonstrated that in single cultures of Caco-2 and THP-1 cells treated with κ-CGN, the cytotoxicity and the secretion levels of IL-1β, IL-6 and TNF-α were low. In the co-culture system, however, κ-CGN treatment resulted in apoptosis and reduced the transepithelial electrical resistance of the Caco-2 cell monolayers. The secretion levels of TNF-α, IL-1β and IL-6 from the two cell types were increased significantly by κ-CGN treatment. Furthermore, pretreatment of the co-culture system with anti-TNF receptor 1 antibody suppressed the κ-CGN-induced apoptosis and attenuated the changes in the levels of IL-6 and IL-1β in the Caco-2 monolayers. This study indicated that κ-CGN-induced TNF-α secretion is the main contributor to cellular damage in Caco-2 monolayers exposed to κ-CGN.

Keywords: κ-carrageenan; colitis inflammation; co-culture; Caco-2 monolayers; TNF-α.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Annexin A5 / metabolism
  • Antibodies / pharmacology
  • Apoptosis / drug effects
  • Caco-2 Cells
  • Carrageenan / pharmacology*
  • Cell Communication / drug effects*
  • Cell Death / drug effects
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Coculture Techniques
  • Cytokines / metabolism
  • Electric Impedance
  • Enterocytes / drug effects
  • Enterocytes / metabolism
  • Enterocytes / pathology*
  • Fluorescein-5-isothiocyanate / metabolism
  • Humans
  • Inflammation Mediators / metabolism
  • Leukocytes / cytology*
  • Leukocytes / drug effects
  • Leukocytes / metabolism
  • Necrosis
  • Receptors, Tumor Necrosis Factor, Type I / immunology
  • Time Factors

Substances

  • Annexin A5
  • Antibodies
  • Cytokines
  • Inflammation Mediators
  • Receptors, Tumor Necrosis Factor, Type I
  • Carrageenan
  • Fluorescein-5-isothiocyanate