N-Acetyl-D-glucosamine oligosaccharides induce mucin secretion from colonic tissue and induce differentiation of human keratinocytes

J Pharm Pharmacol. 2008 Feb;60(2):197-204. doi: 10.1211/jpp.60.2.0008.

Abstract

Chitin oligosaccharides (DP2, DP3, DP4, DP5 and DP7) were investigated for their effects on epithelial cells and tissue (skin keratinocytes in-vitro and ex-vivo, and gastrointestinal epithelial membranes exvivo). Oligomers DP2, DP3 and DP5 at 10microg mL(-1) significantly stimulated the mitochondrial activity of cultured keratinocytes in-vitro (primary cells and HaCaT cell line), with highest activity observed for the pentamer (150% of untreated control). The effects were dose dependent. This higher energy status of primary cells was triggered into a higher differentiation status, as determined by the early and late differentiation markers keratins K1/K10 and involucrin, respectively. In contrast, increased mitogenic cell proliferation was not induced by the oligosaccharides. Toxic effects on keratinocytes were absent. Additionally for the first time a mucin-stimulating effect of chitin oligosaccharides DP3 and DP5 was observed in an ex-vivo model based on intestinal epithelial mucosa tissue. Mucin secretion was time dependent, leading to the secretion of polymers comparable to those normally secreted under physiological conditions. Mucin induction was observed from colonic tissue isolated from humans and pigs. Also, porcine stomach mucosa was stimulated by DP5, while ileum tissue reacted to only a minor extent. Potential developments towards products with wound-healing capacity and activity against chronic bowel disease are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Chitin / administration & dosage
  • Chitin / chemistry
  • Chitin / pharmacology*
  • Dose-Response Relationship, Drug
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gastrointestinal Tract / cytology
  • Gastrointestinal Tract / metabolism
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mucins / drug effects*
  • Mucins / metabolism
  • Oligosaccharides / administration & dosage
  • Oligosaccharides / chemistry
  • Oligosaccharides / pharmacology*
  • Swine
  • Time Factors

Substances

  • Mucins
  • Oligosaccharides
  • Chitin