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Bacteroides fragilis Toxin Induces IL-8 Secretion in HT29/C1 Cells through Disruption of E-cadherin Junctions

  • Hwang, Soonjae (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju) ;
  • Gwon, Sun-Yeong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju) ;
  • Kim, Myung Sook (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju) ;
  • Lee, Seunghyung (Department of Anatomy & Cell Biology and The Sol Sherry Thrombosis Research Center, Temple University School of Medicine) ;
  • Rhee, Ki-Jong (Department of Biomedical Laboratory Science, College of Health Sciences, Yonsei University at Wonju)
  • Received : 2013.09.03
  • Accepted : 2013.09.27
  • Published : 2013.10.31
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Abstract

Enterotoxigenic Bacteroides fragilis (ETBF) is a human gut commensal bacteria that causes inflammatory diarrhea and colitis. ETBF also promotes colorectal tumorigenesis in the Min mouse model. The key virulence factor is a secreted metalloprotease called B. fragilis toxin (BFT). BFT induces E-cadherin cleavage, cell rounding, activation of the ${\beta}$-catenin pathway and secretion of IL-8 in colonic epithelial cells. However, the precise mechanism by which these processes occur and how these processes are interrelated is still unclear. E-cadherin form homophilic interactions which tethers adjacent cells. Loss of E-cadherin results in detachment of adjacent cells. Prior studies have suggested that BFT induces IL-8 expression by inducing E-cadherin cleavage; cells that do not express E-cadherin do not secrete IL-8 in response to BFT. In the current study, we found that HT29/C1cells treated with dilute trypsin solution induced E-cadherin degradation and IL-8 secretion, consistent with the hypothesis that E-cadherin cleavage causes IL-8 secretion. However, physical damage to the cell monolayer did not induce IL-8 secretion. We also show that EDTA-mediated disruption of E-cadherin interactions without E-cadherin degradation was sufficient to induce IL-8 secretion. Finally, we determined that HT29/C1 cells treated with LiCl (${\beta}$-catenin activator) induced IL-8 secretion in a dose-dependent and time-dependent manner. Taken together, our results suggest that BFT induced IL-8 secretion may occur by the following process: E-cadherin cleavage, disruption of cellular interactions, activation of the ${\beta}$-catenin pathway and IL-8 expression. However, we further propose that E-cadherin cleavage per se may not be required for BFT induced IL-8 secretion.

Keywords

References

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