Bacteroides fragilis Toxin Induces IL-8 Secretion in HT29/C1 Cells through Disruption of E-cadherin Junctions.
- Author:
Soonjae HWANG
1
;
Sun Yeong GWON
;
Myung Sook KIM
;
Seunghyung LEE
;
Ki Jong RHEE
Author Information
- Publication Type:Brief Communication
- Keywords: Bacteroides fragilis toxin; Interleukin-8; E-cadherin; beta-catenin; EDTA; LiCl
- MeSH: Animals; Bacteria; Bacterial Toxins; Bacteroides fragilis*; Bacteroides*; beta Catenin; Cadherins*; Cell Transformation, Neoplastic; Colitis; Colon; Diarrhea; Edetic Acid; Epithelial Cells; Fibrinogen; Humans; Interleukin-8*; Metalloendopeptidases; Mice; Trypsin
- From:Immune Network 2013;13(5):213-217
- CountryRepublic of Korea
- Language:English
- 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.
