scholarly journals Toll-Like Receptor 2 andMuc2Expression on Human Intestinal Epithelial Cells by Gymnophalloides seoi Adult Antigen

2010 ◽  
Vol 96 (1) ◽  
pp. 58-66 ◽  
Author(s):  
Ki-Deok Lee ◽  
Sang-Mee Guk ◽  
Jong-Yil Chai
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
Human Intestinal Epithelial Cells ◽  
Toll Like Receptor 2

Flagellin-induced tolerance of the Toll-like receptor 5 signaling pathway in polarized intestinal epithelial cells

2007 ◽  
Vol 292 (3) ◽  
pp. G767-G778 ◽  
Author(s):  
Jun Sun ◽  
Pamela E. Fegan ◽  
Anjali S. Desai ◽  
James L. Madara ◽  
Michael E. Hobert
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Prior Exposure ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
Proinflammatory Response ◽  
Gram Negative ◽  
Human Intestinal Epithelial Cells ◽  
Induced Tolerance ◽  
Toll Like Receptor 5

Salmonella typhimurium is a gram-negative enteric pathogen that invades the mucosal epithelium and is associated with diarrheal illness in humans. Flagellin from S. typhimurium and other gram-negative bacteria has been shown to be the predominant proinflammatory mediator through activation of the basolateral Toll-like receptor 5 (TLR5). Recent evidence has shown that prior exposure can render immune cells tolerant to subsequent challenges by TLR ligands. Accordingly, we examined whether prior exposure to purified flagellin would render human intestinal epithelial cells insensitive to future contact. We found that flagellin-induced tolerance is common to polarized epithelial cells and prevents further activation of proinflammatory signaling cascades by both purified flagellin and Salmonella bacteria but does not affect TNF-α stimulation of the same pathways. Flagellin tolerance is a rapid process that does not require protein synthesis, and that occurs within 1 to 2 h of flagellin exposure. Prolonged flagellin exposure blocks activation of the NF-κB, MAPK, and phosphoinositol 3-kinase signaling pathways and results in the internalization of a fraction of the basolateral TLR5 without affecting the polarity or total expression of TLR5. After removal of flagellin, cells require more than 24 h to fully recover their ability to mount a normal proinflammatory response. We have found that activation of phosphoinositol 3-kinase and Akt by flagellin has a small damping effect in the early stages of flagellin signaling but is not responsible for tolerance. Our study indicates that inhibition of TLR5-associated IL-1 receptor-associated kinase-4 activity occurs during the development of flagellin tolerance and is likely to be the cause of tolerance.

scholarly journals Campylobacter-Induced Interleukin-8 Secretion in Polarized Human Intestinal Epithelial Cells Requires Campylobacter-Secreted Cytolethal Distending Toxin- and Toll-Like Receptor-Mediated Activation of NF-κB

2008 ◽  
Vol 76 (10) ◽  
pp. 4498-4508 ◽  
Author(s):  
Jie Zheng ◽  
Jianghong Meng ◽  
Shaohua Zhao ◽  
Ruby Singh ◽  
Wenxia Song
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelium ◽  
Intestinal Epithelial Cells ◽  
Interleukin 8 ◽  
Cytolethal Distending Toxin ◽  
Intestinal Epithelial ◽  
Toll Like Receptor ◽  
T84 Cells ◽  
Human Intestinal Epithelial Cells ◽  
Tnf Α

ABSTRACT Campylobacter jejuni and Campylobacter coli colonize and infect the intestinal epithelium and cause acute inflammatory diarrhea. The intestinal epithelium serves as a physical barrier to, and a sensor of, bacterial infection by secreting proinflammatory cytokines. This study examined the mechanisms for Campylobacter-induced secretion of the proinflammatory chemokine interleukin-8 (IL-8) by using polarized T84 human colonic epithelial cells as a model. C. jejuni increased the secretion of both IL-8 and tumor necrosis factor alpha (TNF-α) in polarized epithelial cells. However, the increase in IL-8 secretion was independent of Campylobacter-stimulated TNF-α secretion. Polarized T84 cells secreted IL-8 predominantly to the basolateral medium independently of the inoculation direction. While there was a significant correlation between the levels of IL-8 secretion and Campylobacter invasion, all 11 strains tested increased IL-8 secretion by polarized T84 cells despite their differences in adherence, invasion, and transcytosis efficiencies. Cell-free supernatants of Campylobacter-T84-cell culture increased IL-8 secretion to levels similar to those induced by live bacterial inoculation. The ability of the supernatant to induce IL-8 secretion was reduced by flagellum and cytolethal distending toxin (CDT) gene mutants, treatment of the supernatant with protease K or heat, or treatment of T84 cells with the Toll-like receptor (TLR) inhibitor MyD88 inhibitory peptide or chloroquine. NF-κB inhibitors or cdtB mutation plus MyD88 inhibitor, but not flaA cdtB double mutations, abolished the ability of the supernatant to induce IL-8 secretion. Taken together, our results demonstrate that Campylobacter-induced IL-8 secretion requires functional flagella and CDT and depends on the activation of NF-κB through TLR signaling and CDT in human intestinal epithelial cells.

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