Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFalpha-dependent manner

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2010
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Noti, Mario
Corazza, Nadia
Tuffin, Gèrald
Schoonjans, Kristina
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The FASEB Journal. 2010, 24(5), pp. 1340-1346. ISSN 0892-6638. eISSN 1530-6860. Available under: doi: 10.1096/fj.09-140913
Zusammenfassung

Stringent control of immune responses in the intestinal mucosa is critical for the maintenance of immune homeostasis and prevention of tissue damage, such as observed during inflammatory bowel disease. Intestinal epithelial cells, primarily thought to form a simple physical barrier, critically regulate intestinal immune cell functions by producing immunoregulatory glucocorticoids on T-cell activation. In this study we investigated whether stimulation of cells of the innate immune system results in the induction of intestinal glucocorticoids synthesis and what role TNF-α plays in this process. Stimulation of the innate immune system with lipopolysaccharide (LPS) led to an up-regulation of colonic steroidogenic enzymes and the induction of intestinal glucocorticoid synthesis. The observed induction was dependent on macrophage effector functions, as depletion of macrophages using clodronate-containing liposomes, but not absence of T and B cells, inhibited intestinal glucocorticoid synthesis. LPS-induced glucocorticoid synthesis was critically dependent on TNF-α as it was significantly decreased in TNF-α-deficient animals. Both TNF receptor-1 and -2 were found to be equally involved in LPS- and T-cell-induced intestinal GC synthesis. These results describe a novel and critical role of TNF-α in immune cell-induced intestinal glucocorticoid synthesis.—Noti, M., Corazza, N., Tuffin, G., Schoonjans, K., Brunner, T. Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFα-dependent manner.

Zusammenfassung in einer weiteren Sprache
Fachgebiet (DDC)
570 Biowissenschaften, Biologie
Schlagwörter
inflammatory bowel disease, tumor necrosis factor α, intestinal epithelial cells, macrophages, TNF receptors
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ISO 690NOTI, Mario, Nadia CORAZZA, Gèrald TUFFIN, Kristina SCHOONJANS, Thomas BRUNNER, 2010. Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFalpha-dependent manner. In: The FASEB Journal. 2010, 24(5), pp. 1340-1346. ISSN 0892-6638. eISSN 1530-6860. Available under: doi: 10.1096/fj.09-140913
BibTex
@article{Noti2010-05Lipop-13536,
  year={2010},
  doi={10.1096/fj.09-140913},
  title={Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFalpha-dependent manner},
  number={5},
  volume={24},
  issn={0892-6638},
  journal={The FASEB Journal},
  pages={1340--1346},
  author={Noti, Mario and Corazza, Nadia and Tuffin, Gèrald and Schoonjans, Kristina and Brunner, Thomas}
}
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