Collagen peptides ameliorate intestinal epithelial barrier dysfunction in immunostimulatory Caco-2 cell monolayers via enhancing tight junctions

Food Funct. 2017 Mar 22;8(3):1144-1151. doi: 10.1039/c6fo01347c.

Abstract

Dysfunction of the intestinal barrier plays a key role in the pathogenesis of inflammatory bowel disease (IBD) and multiple organ failure. The effect of Alaska pollock skin-derived collagen and its 3 tryptic hydrolytic fractions, HCP (6 kDa retentate), MCP (3 kDa retentate) and LCP (3 kDa permeate) on TNF-α induced barrier dysfunction was investigated in Caco-2 cell monolayers. TNF-α induced barrier dysfunction was significantly attenuated by the collagen and its peptide fractions, especially LCP, compared to TNF-α treated controls (P < 0.05). Compared to a negative control, 24 h pre-incubation with 2 mg mL-1 LCP significantly alleviated the TNF-α induced breakdown of the tight junction protein ZO-1 and occludin and inhibited MLC phosphorylation and MLCK expression. The activation of NFκB and Elk-1 was suppressed by LCP. Thus, collagen peptides may attenuate TNF-α induced barrier dysfunction of Caco-2 cells by inhibiting the NFκB and ERK1/2-mediated MLCK pathway with associated decreases in ZO-1 and occludin protein expression.

MeSH terms

  • Animals
  • Caco-2 Cells
  • Collagen / administration & dosage
  • Collagen / chemistry*
  • Fish Proteins / administration & dosage
  • Fish Proteins / chemistry*
  • Fish Proteins / immunology
  • Fishes
  • Humans
  • Inflammatory Bowel Diseases / drug therapy
  • Inflammatory Bowel Diseases / genetics
  • Inflammatory Bowel Diseases / immunology*
  • Intestines / drug effects*
  • Intestines / immunology
  • Occludin / genetics
  • Occludin / immunology
  • Peptides / administration & dosage*
  • Peptides / chemistry
  • Skin / chemistry*
  • Tight Junctions / drug effects*
  • Tight Junctions / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Fish Proteins
  • Occludin
  • Peptides
  • Tumor Necrosis Factor-alpha
  • Collagen