Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFalpha-dependent manner

Noti, Mario; Corazza, Nadia; Tuffin, Gérald; Schoonjans, Kristina; Brunner, Thomas (2010). Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFalpha-dependent manner. FASEB journal, 24(5), pp. 1340-6. Bethesda, Md.: Federation of American Societies for Experimental Biology 10.1096/fj.09-140913

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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-alpha 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-alpha as it was significantly decreased in TNF-alpha-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-alpha in immune cell-induced intestinal glucocorticoid synthesis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Service Sector > Institute of Pathology

UniBE Contributor:

Corazza, Nadia and Brunner, Thomas

ISSN:

0892-6638

Publisher:

Federation of American Societies for Experimental Biology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:09

Last Modified:

04 May 2014 23:04

Publisher DOI:

10.1096/fj.09-140913

PubMed ID:

20056718

Web of Science ID:

000277158900007

URI:

https://boris.unibe.ch/id/eprint/799 (FactScience: 200871)

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