TLR signaling at the intestinal epithelial interface

Maria T Abreu, Lisa S. Thomas, Elizabeth T. Arnold, Katie Lukasek, Kathrin S. Michelsen, Moshe Arditi

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

The intestinal epithelium provides a critical interface between lumenal bacteria and the mucosal immune system. Whereas normal commensal flora do not trigger acute inflammation, pathogenic bacteria trigger a potent inflammatory response. Our studies emanate from the hypothesis that the intestinal epithelium is normally hyporesponsive to commensal pathogen-associated molecular patterns (PAMPs) such as LPS. Our data demonstrate that normal human colonic epithelial cells and lamina propria cells express low levels of TLR4 and its co-receptor MD-2. This expression pattern is mirrored by intestinal epithelial cell (IEC) lines. Co-expression of TLR4 and MD-2 is necessary and sufficient for LPS responsiveness in IEC. Moreover, LPS sensing occurs along the basolateral membrane of polarized IEC in culture. Expression of MD-2 is regulated by IFN-γ. Cloning of the MD-2 promoter demonstrates that promoter activity is increased by IFN-γ and blocked by the STAT inhibitor SOCS3. We conclude from our studies that the intestinal epithelium down-regulates expression of TLR4 and MD-2 and is LPS unresponsive. The Th1 cytokine IFN-γ up-regulates expression of MD-2 in a STAT-dependent fashion. The results of our studies have important implications for understanding human inflammatory bowel diseases.

Original languageEnglish
Pages (from-to)322-331
Number of pages10
JournalJournal of Endotoxin Research
Volume9
Issue number5
DOIs
StatePublished - Oct 10 2003
Externally publishedYes

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Intestinal Mucosa
Epithelial Cells
Bacteria
Cloning
Immune system
Inflammatory Bowel Diseases
Organism Cloning
Immune System
Mucous Membrane
Up-Regulation
Down-Regulation
Cell Culture Techniques
Cytokines
Inflammation
Membranes
Cell Line

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Toxicology

Cite this

Abreu, M. T., Thomas, L. S., Arnold, E. T., Lukasek, K., Michelsen, K. S., & Arditi, M. (2003). TLR signaling at the intestinal epithelial interface. Journal of Endotoxin Research, 9(5), 322-331. https://doi.org/10.1179/096805103225002593

TLR signaling at the intestinal epithelial interface. / Abreu, Maria T; Thomas, Lisa S.; Arnold, Elizabeth T.; Lukasek, Katie; Michelsen, Kathrin S.; Arditi, Moshe.

In: Journal of Endotoxin Research, Vol. 9, No. 5, 10.10.2003, p. 322-331.

Research output: Contribution to journalArticle

Abreu, MT, Thomas, LS, Arnold, ET, Lukasek, K, Michelsen, KS & Arditi, M 2003, 'TLR signaling at the intestinal epithelial interface', Journal of Endotoxin Research, vol. 9, no. 5, pp. 322-331. https://doi.org/10.1179/096805103225002593
Abreu MT, Thomas LS, Arnold ET, Lukasek K, Michelsen KS, Arditi M. TLR signaling at the intestinal epithelial interface. Journal of Endotoxin Research. 2003 Oct 10;9(5):322-331. https://doi.org/10.1179/096805103225002593
Abreu, Maria T ; Thomas, Lisa S. ; Arnold, Elizabeth T. ; Lukasek, Katie ; Michelsen, Kathrin S. ; Arditi, Moshe. / TLR signaling at the intestinal epithelial interface. In: Journal of Endotoxin Research. 2003 ; Vol. 9, No. 5. pp. 322-331.
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