Disruption of epithelial barrier by quorum-sensing N-3-(oxododecanoyl)-homoserine lactone is mediated by matrix metalloproteinases

Sung Yong Eum, Dima Jaraki, Luc Bertrand, Ibolya E. András, Michal Toborek

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


The intestinal epithelium forms a selective barrier maintained by tight junctions (TJs) and separating the luminal environment from the submucosal tissues. N-acylhomoserine lactone (AHL) quorum-sensing molecules produced by gram-negative bacteria in the gut can influence homeostasis of the host intestinal epithelium. In the present study, we evaluated the regulatory mechanisms affecting the impact of two representative long- and short-chain AHLs, N-3-(oxododecanoyl)- homoserine lactone (C12-HSL) and N-butyryl homoserine lactone (C4-HSL), on barrier function of human intestinal epithelial Caco-2 cells. Treatment with C12-HSL, but not with C4-HSL, perturbed Caco-2 barrier function; the effect was associated with decreased levels of the TJ proteins occludin and tricellulin and their delocalization from the TJs. C12-HSL also induced matrix metalloprotease (MMP)-2 and MMP-3 activation via lipid raft- and proteaseactivated receptor (PAR)-dependent signaling. Pretreatment with lipid raft disruptors, PAR antagonists, or MMP inhibitors restored the C12-HSL-induced loss of the TJ proteins and increased permeability of Caco-2 cell monolayers. These results indicate that PAR/lipid raft-dependent MMP-2 and -3 activation followed by degradation of occludin and tricellulin are involved in C12-HSL-induced alterations of epithelial paracellular barrier functions.

Original languageEnglish (US)
Pages (from-to)G992-G1001
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Issue number11
StatePublished - Jun 1 2014


  • Intestinal epithelium
  • Matrix metalloprotease
  • N-acylhomoserine lactone
  • Occludin
  • Tricellulin

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology
  • Hepatology
  • Gastroenterology


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