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Vibrio cholerae OmpU induces IL-8 expression in human intestinal epithelial cells

Jae Seung Yang1, Jun Ho Jeon2, Mi Seon Jang3

  • 1Clinical Research Laboratory, Sciences Unit, International Vaccine Institute, Seoul, Republic of Korea.

Molecular Immunology
|November 18, 2017
PubMed

Insights

Vibrio cholerae outer membrane protein U (OmpU) triggers interleukin-8 (IL-8) secretion in human intestinal cells. This OmpU-mediated IL-8 induction is crucial for V. cholerae

Area of Science:

  • Microbiology
  • Immunology
  • Cell Biology

Background:

  • Vibrio cholerae infection leads to intestinal inflammation, but the underlying molecular mechanisms are not fully understood.
  • Outer membrane protein U (OmpU) is a key factor in V. cholerae's interaction with host immunity.
  • Interleukin-8 (IL-8) is a critical chemokine involved in recruiting immune cells during intestinal inflammation.

Purpose of the Study:

  • To investigate the role of V. cholerae OmpU in inducing IL-8 expression in human intestinal epithelial cells (HT-29).
  • To elucidate the signaling pathways and cellular mechanisms involved in OmpU-mediated IL-8 production.

Main Methods:

  • Treatment of HT-29 cells with recombinant OmpU (rOmpU) and V. cholerae strains.
  • Measurement of IL-8 mRNA and protein levels using quantitative PCR and ELISA.
  • Investigation of cellular uptake mechanisms (lipid rafts, clathrin-coated pits) and signaling pathways (ERK1/2, p38, JNK).
  • Comparison of IL-8 expression and bacterial adherence between wild-type and ompU-deficient V. cholerae strains.

Main Results:

  • Recombinant OmpU induced dose- and time-dependent IL-8 expression at both mRNA and protein levels in HT-29 cells.
  • IL-8 secretion occurred via both apical and basolateral routes upon apical rOmpU exposure.
  • OmpU-mediated IL-8 induction involved lipid raft-dependent endocytosis and activation of ERK1/2 and p38 kinase pathways.
  • V. cholerae lacking OmpU showed reduced IL-8 expression and adherence to HT-29 cells.

Conclusions:

  • V. cholerae OmpU plays a significant role in initiating intestinal inflammation by inducing IL-8 expression in human intestinal epithelial cells.
  • OmpU utilizes specific cellular pathways, including lipid rafts and MAPK signaling, to modulate the host immune response.
  • Understanding OmpU's function provides insights into V. cholerae pathogenesis and potential therapeutic targets.
Keywords:
AdherenceIL-8InflammationIntestinal epithelial cellsOmpUVibrio cholerae

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