Transcription Factor NF-κB Signals Antianoikic Function of Trefoil Factor 3 on Intestinal Epithelial Cells

2000 ◽  
Vol 274 (3) ◽  
pp. 576-582 ◽  
Author(s):  
Yi-Hua Chen ◽  
Yu Lu ◽  
Isabelle G. De Plaen ◽  
Li-Ya Wang ◽  
Xiao-Di Tan
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Trefoil Factor ◽  
Trefoil Factor 3

scholarly journals TFF3 modulates NF-κB and a novel negative regulatory molecule of NF-κB in intestinal epithelial cells via a mechanism distinct from TNF-α

2005 ◽  
Vol 289 (5) ◽  
pp. C1085-C1093 ◽  
Author(s):  
Ya-Qin Zhu ◽  
Xiao-Di Tan
Keyword(s):  
Tumor Necrosis Factor ◽  
Epithelial Cells ◽  
Tumor Necrosis ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Trefoil Factor ◽  
Trefoil Factor 3 ◽  
Twist Protein ◽  
Factor Α ◽  
Necrosis Factor

Trefoil factor 3 (intestinal trefoil factor) is a cytoprotective factor in the gut. Herein we compared the effect of trefoil factor 3 with tumor necrosis factor-α on 1) activation of NF-κB in intestinal epithelial cells; 2) expression of Twist protein (a molecule essential for downregulation of nuclear factor-κB activity in vivo); and 3) production of interleukin-8. We showed that Twist protein is constitutively expressed in intestinal epithelial cells. Tumor necrosis factor-α induced persistent degradation of Twist protein in intestinal epithelial cells via a signaling pathway linked to proteasome, which was associated with prolonged activation of NF-κB. In contrast to tumor necrosis factor, trefoil factor 3 triggered transient activation of NF-κB and prolonged upregulation of Twist protein in intestinal epithelial cells via an ERK kinase-mediated pathway. Unlike tumor necrosis factor-α, transient activation of NF-κB by trefoil factor 3 is not associated with induction of IL-8 in cells. To examine the role of Twist protein in intestinal epithelial cells, we silenced the Twist expression by siRNA. Our data showed that trefoil factor 3 induced interleukin-8 production after silencing Twist in intestinal epithelial cells. Together, these observations indicated that 1) trefoil factor 3 triggers a diverse signal from tumor necrosis factor-α on the activation of NF-κB and its associated molecules in intestinal epithelial cells; and 2) trefoil factor 3-induced Twist protein plays an important role in the modulation of inflammatory cytokine production in intestinal epithelial cells.

Activation of NF-κB in intestinal epithelial cells by enteropathogenicEscherichia coli

1997 ◽  
Vol 273 (4) ◽  
pp. C1160-C1167 ◽  
Author(s):  
Suzana D. Savkovic ◽  
Athanasia Koutsouris ◽  
Gail Hecht
Keyword(s):  
Transcription Factor ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Bacterial Flora ◽  
Inflammatory Cells ◽  
Initial Response ◽  
Intestinal Epithelial ◽  
E Coli ◽  
Normal Bacterial Flora ◽  
First Time

The initial response to infection is recruitment of acute inflammatory cells to the involved site. Interleukin (IL)-8 is the prototypical effector molecule for this process. Transcription of the IL-8 gene is primarily governed by the nuclear transcription factor (NF)-κB. Intestinal epithelial cells produce IL-8 in response to infection by enteric pathogens yet remain quiescent in a milieu where they are literally bathed in normal bacterial flora. We therefore sought to investigate NF-κB activation in response to enteropathogenic Escherichia coli (EPEC), nonpathogenic E. coli, and bacterial lipopolysaccharide in an intestinal epithelial cell (T84) model and to determine whether EPEC-induced activation of NF-κB factor is causally linked to IL-8 production. We report herein that NF-κB is activated by EPEC, yet such a response is not extended to nonpathogenic organisms or purified E. coli lipopolysaccharide. Transcription factor decoys significantly diminished IL-8 production in response to EPEC, demonstrating a causal relationship. Furthermore, deletion of specific EPEC virulence genes abrogates the NF-κB-activating property of this pathogen, suggesting that specific bacterial factors are crucial for inducing this response. These studies show for the first time that infection of intestinal epithelial cells with EPEC activates NF-κB, which in turn initiates IL-8 transcription, and highlight the differential response of these cells to bacterial pathogens vs. nonpathogens.

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