Responsiveness of intestinal epithelial cell lines to lipopolysaccharide is correlated with Toll-like receptor 4 but not Toll-like receptor 2 or ... View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2003-01

AUTHORS

Ulrich Böcker, Oleksandr Yezerskyy, Peter Feick, Tobias Manigold, Asit Panja, Uwe Kalina, Frank Herweck, Siegbert Rossol, Manfred V. Singer

ABSTRACT

BACKGROUND AND AIMS: Luminal bacteria have been implicated in the pathogenesis of inflammatory bowel diseases. Exposure of intestinal epithelial cells (IEC) to bacterial components potentially initiates intestinal inflammation by release of chemokines and recruitment of inflammatory cells. We analyzed receptor expression and signaling pathways involved in activation of human primary IEC and carcinoma-derived cell lines by lipopolysaccharide (LPS). MATERIALS AND METHODS: HT-29/p, HT-29/MTX, and Caco-2 cells were stimulated by LPS. IL-8 content in supernatants was analyzed by ELISA, and expression of CD14, Toll-like receptor (TLR) 2 and TLR 4 was determined by RT-PCR. Presence of TLR 4 protein was assessed by western blot analysis. LPS response was modulated by sCD14, LPS-binding protein, neutralization of CD14, and inhibitors of early signal activation. RESULTS: LPS dose-dependently induced secretion of IL-8 in undifferentiated HT-29/p cells while Caco-2 and permanently differentiated HT-29/MTX cells were unresponsive. Differently to HT-29/MTX, both HT-29/p and Caco-2 cells constitutively expressed transcripts for CD14. However, CD14 was not required for LPS-mediated induction of IL-8 in HT-29/p cells since neutralizing anti-CD14 antibodies left IL-8 levels unchanged. Unresponsiveness of Caco-2 and HT-29/MTX cells to LPS persisted in the presence of sCD14 and/or LPS-binding protein. Neither cell line expressed TLR 2 transcripts while only responsive HT-29/p cells expressed TLR 4 mRNA and TLR 4 protein. Butyrate down-regulated TLR 4 expression and significantly diminished LPS-dependent IL-8 secretion. Inhibition of G protein dependent kinase activation reduced IL-8 levels to 50%; the phosphatidyl-inositol-3'-kinase inhibitor LY294002 abrogated the response. CONCLUSION: Responsiveness of IEC lines to LPS is positively correlated with TLR 4 expression. Strategies targeting TLR 4 expression or TLR 4 mediated signaling may antagonize IEC activation by LPS. More... »

PAGES

25-32

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s00384-002-0415-6

DOI

http://dx.doi.org/10.1007/s00384-002-0415-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1016697468

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/12458377


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N-Triples is a line-based linked data format ideal for batch operations.

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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1007/s00384-002-0415-6'


 

This table displays all metadata directly associated to this object as RDF triples.

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