scholarly journals Lamina Propria CD4+T Lymphocytes Synergize with Murine Intestinal Epithelial Cells to Enhance Proinflammatory Response Against an Intracellular Pathogen

2002 ◽  
Vol 168 (6) ◽  
pp. 2988-2996 ◽  
Author(s):  
Franck J. D. Mennechet ◽  
Lloyd H. Kasper ◽  
Nicolas Rachinel ◽  
Wen Li ◽  
Alain Vandewalle ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Epithelial Cells ◽  
Lamina Propria ◽  
Intestinal Epithelial Cells ◽  
Intracellular Pathogen ◽  
Intestinal Epithelial ◽  
Proinflammatory Response

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 Endoplasmic Reticulum Stress and Intestinal Inflammation: A Perilous Union

2020 ◽  
Vol 11 ◽  
Author(s):  
Sanchez Preethi Eugene ◽  
Vadde Sudhakar Reddy ◽  
Jamma Trinath
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Er Stress ◽  
Lamina Propria ◽  
Immune Cells ◽  
Intestinal Inflammation ◽  
Intestinal Epithelial Cells ◽  
Pharmacological Intervention ◽  
Intestinal Epithelial ◽  
Exogenous Origin

The intestinal tract encompasses the largest mucosal surface fortified with a fine layer of intestinal epithelial cells along with highly sophisticated network of the lamina propria immune cells that are indispensable to sustain gut homeostasis. However, it can be challenging to uphold homeostasis when these cells in the intestine are perpetually exposed to insults of both endogenous and exogenous origin. The complex networking and dynamic microenvironment in the intestine demand highly functional cells ultimately burdening the endoplasmic reticulum (ER) leading to ER stress. Unresolved ER stress is one of the primary contributors to the pathogenesis of inflammatory bowel diseases (IBD). Studies also suggest that ER stress can be the primary cause of inflammation and/or the consequence of inflammation. Therefore, understanding the patterns of expression of ER stress regulators and deciphering the intricate interplay between ER stress and inflammatory pathways in intestinal epithelial cells in association with lamina propria immune cells contribute toward the development of novel therapies to tackle IBD. This review provides imperative insights into the molecular markers involved in the pathogenesis of IBD by potentiating ER stress and inflammation and briefly describes the potential pharmacological intervention strategies to mitigate ER stress and IBD. In addition, genetic mutations in the biomarkers contributing to abnormalities in the ER stress signaling pathways further emphasizes the relevance of biomarkers in potential treatment for IBD.

PKCζ participates in activation of inflammatory response induced by enteropathogenicE. coli

2003 ◽  
Vol 285 (3) ◽  
pp. C512-C521 ◽  
Author(s):  
Suzana D. Savkovic ◽  
Athanasia Koutsouris ◽  
Gail Hecht
Keyword(s):  
Epithelial Cells ◽  
Kinase Activity ◽  
Intestinal Epithelial Cells ◽  
Fold Increase ◽  
Serine Phosphorylation ◽  
Intestinal Epithelial ◽  
Proinflammatory Response ◽  
Independent Events ◽  
Iκb Kinase ◽  
Iκbα Phosphorylation

We showed previously that enteropathogenic Escherichia coli (EPEC) infection of intestinal epithelial cells induces inflammation by activating NF-κB and upregulating IL-8 expression. We also reported that extracellular signal-regulated kinases (ERKs) participate in EPEC-induced NF-κB activation but that other signaling molecules such as PKCζ may be involved. The aim of this study was to determine whether PKCζ is activated by EPEC and to investigate whether it also plays a role in EPEC-associated inflammation. EPEC infection induced the translocation of PKCζ from the cytosol to the membrane and its activation as determined by kinase activity assays. Inhibition of PKCζ by the pharmacological inhibitor rottlerin, the inhibitory myristoylated PKCζ pseudosubstrate (MYR-PKCζ-PS), or transient expression of a nonfunctional PKCζ significantly suppressed EPEC-induced IκBα phosphorylation. Although PKCζ can activate ERK, MYR-PKCζ-PS had no effect on EPEC-induced stimulation of this pathway, suggesting that they are independent events. PKCζ can regulate NF-κB activation by interacting with and activating IκB kinase (IKK). Coimmunoprecipitation studies showed that the association of PKCζ and IKK increased threefold 60 min after infection. Kinase activity assays using immunoprecipitated PKCζ-IKK complexes from infected intestinal epithelial cells and recombinant IκBα as a substrate showed a 2.5-fold increase in IκBα phosphorylation. PKCζ can also regulate NF-κB by serine phosphorylation of the p65 subunit. Serine phosphorylation of p65 was increased after EPEC infection but could not be consistently attenuated by MYR-PKCζ-PS, suggesting that other signaling events may be involved in this particular arm of NF-κB regulation. We speculate that EPEC infection of intestinal epithelial cells activates several signaling pathways including PKCζ and ERK that lead to NF-κB activation, thus ensuring the proinflammatory response.

scholarly journals Cell Surface-Associated Elongation Factor Tu Mediates the Attachment of Lactobacillus johnsonii NCC533 (La1) to Human Intestinal Cells and Mucins

2004 ◽  
Vol 72 (4) ◽  
pp. 2160-2169 ◽  
Author(s):  
Dominique Granato ◽  
Gabriela E. Bergonzelli ◽  
Raymond David Pridmore ◽  
Laure Marvin ◽  
Martine Rouvet ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Binding Capacity ◽  
Elongation Factor ◽  
Mass Spectrometry Analysis ◽  
Intestinal Cells ◽  
Elongation Factor Tu ◽  
Intestinal Epithelial ◽  
Lactobacillus Johnsonii ◽  
Proinflammatory Response

ABSTRACT The aim of this work was to identify Lactobacillus johnsonii NCC533 (La1) surface molecules mediating attachment to intestinal epithelial cells and mucins. Incubation of Caco-2 intestinal epithelial cells with an L. johnsonii La1 cell wall extract led to the recognition of elongation factor Tu (EF-Tu) as a novel La1 adhesin-like factor. The presence of EF-Tu at the surface of La1 was confirmed by analysis of purified outer surface protein extract by immunoblotting experiments, by electron microscopy, and by enzyme-linked immunosorbent assays of live bacteria. Furthermore, tandem mass spectrometry analysis proved that EF-TU was expressed at the La1 surface as an intact molecule. Using recombinant La1 EF-Tu protein, we were able to determine that its binding to intestinal cells and to mucins is pH dependent. Competition experiments suggested that EF-Tu has an important role in La1 mucin binding capacity. In addition, immunomodulation studies performed on HT29 cells showed that EF-Tu recombinant protein can induce a proinflammatory response in the presence of soluble CD14. Our in vitro results indicate that EF-Tu, through its binding to the intestinal mucosa, might participate in gut homeostasis.

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