Infection of human intestinal epithelial cells by invasive bacteria activates NF-kappa B and increases ICAM-1 expression through NOD1

초록

Background/Aims: Nucleotide-binding oligomerization domain 1 (NOD1) is required for primary intestinal epithelial cells (IECs) to respond to natural mucopeptides secreted by gram-negative bacteria. Infection of human IECs with invasive bacteria up-regulates intercellular adhesion molecule-1 (ICAM-1) expression. However, the role of NOD family members in host defense has been largely unknown. The aim of this study was to determine whether there is a functional role for NOD1 in the up-regulation of ICAM-1 expression in invasive bacteria-infected IECs. Methods: ICAM-1 mRNA expression was compared between controls, Caco-2 or HT29 cells transfected with an empty vector, and IECs stably transfected with a dominant-negative (DN) NOD1. Expression was compared using qualitative reverse transcription polymerase chain reaction (RT-PCR), real-time RT-PCR, and flow cytometry after infection with enteroinvasive Escherichia coli O29: NM or Shigella flexneri. Nuclear factor kB (NF-kappa B) activation was determined by electrophoretic mobility shift assays. Results: DN NOD1 significantly inhibited the up-regulation of ICAM-1 expression in response to an enteroinvasive bacterial infection. The Caco-2 cells transfected with DN NOD1 manifested marked inhibition of NF-kappa B activation in response to E. coli O29: NM infection. Conclusions: Signaling through NOD1 may play an essential role in neutrophil trafficking following infection with enteroinvasive bacteria.

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