Pseudomonas aeruginosa quorum sensing molecule N-(3 oxododecanoyl)-l-homoserine lactone disrupts epithelial barrier integrity of Caco-2 cells

FEBS Lett. 2006 Dec 22;580(30):6921-8. doi: 10.1016/j.febslet.2006.11.057. Epub 2006 Dec 4.

Abstract

Acyl-homoserine lactone (HSL) quorum sensing molecules play an important role in regulation of virulence gene expression in Pseudomonas aeruginosa. Here, we show that 3O-C(12)-HSL can disrupt barrier integrity in human epithelial Caco-2 cells as evidenced by decreased transepithelial electrical resistance (TER), increased paracellular flux, reduction in the expression and distribution of ZO-1 and occludin, and reorganization of F-actin. P. aeruginosa 3O-C(12)-HSL activate p38 and p42/44 kinases, and inhibition of these kinases partly prevented 3O-C(12)-HSL-induced changes in TER, paracellular flux and expression of occludin and ZO-1. These findings demonstrate that P. aeruginosa 3O-C(12)-HSL can modulate tight junction integrity of Caco-2 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / pharmacology
  • Actins / metabolism
  • Caco-2 Cells
  • Cell Adhesion
  • Cell Proliferation
  • Dextrans / pharmacology
  • Electric Impedance
  • Enzyme Activation / drug effects
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Homoserine / analogs & derivatives*
  • Homoserine / pharmacology
  • Humans
  • Membrane Proteins / metabolism
  • Microscopy, Electron, Scanning
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Occludin
  • Phosphoproteins / metabolism
  • Protein Kinase Inhibitors / pharmacology
  • Pseudomonas aeruginosa / chemistry*
  • Quorum Sensing*
  • Zonula Occludens-1 Protein

Substances

  • Actins
  • Dextrans
  • Membrane Proteins
  • N-(3-oxododecanoyl)homoserine lactone
  • OCLN protein, human
  • Occludin
  • Phosphoproteins
  • Protein Kinase Inhibitors
  • TJP1 protein, human
  • Zonula Occludens-1 Protein
  • Homoserine
  • Mitogen-Activated Protein Kinases
  • 4-Butyrolactone