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Lipopolysaccharide induces intestinal glucocorticoid synthesis in a TNFα‐dependent manner
Author(s) -
Noti Mario,
Corazza Nadia,
Tuffin Gérald,
Schoonjans Kristina,
Brunner Thomas
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-140913
Subject(s) - glucocorticoid , lipopolysaccharide , immune system , tumor necrosis factor alpha , innate immune system , glucocorticoid receptor , stimulation , interleukin 22 , intestinal mucosa , inflammation , biology , immunology , chemistry , endocrinology , cytokine , medicine , microbiology and biotechnology , interleukin
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 immunoregu‐latory 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. FASEB J. 24, 1340–1346 (2010). www.fasebj.org