Bacteroides fragilis Toxin Induces Intestinal Epithelial Cell Secretion of Interleukin-8 by the E-Cadherin/β-Catenin/NF-κB Dependent Pathway.
Chang-Gun LeeSoonjae HwangSun-Yeong GwonChanoh ParkMinjeong JoJu-Eun HongKi-Jong RheePublished in: Biomedicines (2022)
Enterotoxigenic Bacteroides fragilis (ETBF) has emerged as a gut microbiome pathogen that can promote colitis associated cancer in humans. ETBF secretes the metalloprotease, B. fragilis toxin (BFT), which can induce ectodomain cleavage of E-cadherin and IL-8 secretion through the β-catenin, NF-κB, and MAPK pathways in intestinal epithelial cells. However, it is still unclear whether E-cadherin cleavage is required for BFT induced IL-8 secretion and the relative contribution of these signaling pathways to IL-8 secretion. Using siRNA knockdown and CRISPR knockout studies, we found that E-cadherin cleavage is required for BFT mediated IL-8 secretion. In addition, genetic ablation of β-catenin indicates that β-catenin is required for the BFT induced increase in transcriptional activity of NF-κB, p65 nuclear localization and early IL-8 secretion. These results suggest that BFT induced β-catenin signaling is upstream of NF-κB activation. However, despite β-catenin gene disruption, BFT still activated the MAPK pathway, suggesting that the BFT induced activation of the MAPK signaling pathway is independent from the E-cadherin/β-catenin/NF-κB pathway. These findings show that E-cadherin and β-catenin play a critical role in acute inflammation following ETBF infection through the inflammatory response to BFT in intestinal epithelial cells.
Keyphrases
- signaling pathway
- epithelial mesenchymal transition
- pi k akt
- oxidative stress
- cell proliferation
- diabetic rats
- induced apoptosis
- high glucose
- drug induced
- lps induced
- escherichia coli
- squamous cell carcinoma
- genome wide
- crispr cas
- gene expression
- liver failure
- dna binding
- intensive care unit
- acute respiratory distress syndrome
- inflammatory response
- extracorporeal membrane oxygenation
- atrial fibrillation
- squamous cell
- aortic dissection