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Publication : TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis.

First Author  Noti M Year  2010
Journal  J Exp Med Volume  207
Issue  5 Pages  1057-66
PubMed ID  20439544 Mgi Jnum  J:160930
Mgi Id  MGI:4456320 Doi  10.1084/jem.20090849
Citation  Noti M, et al. (2010) TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis. J Exp Med 207(5):1057-66
abstractText  Although tumor necrosis factor (alpha) (TNF) exerts proinflammatory activities in a variety of diseases, including inflammatory bowel disease, there is increasing evidence for antiinflammatory actions of TNF. In contrast, glucocorticoids (GCs) are steroid hormones that suppress inflammation, at least in part by regulating the expression and action of TNF. We report that TNF induces extraadrenal production of immunoregulatory GCs in the intestinal mucosa during acute intestinal inflammation. The absence of TNF results in a lack of colonic GC synthesis and exacerbation of dextran sodium sulfate-induced colitis. TNF seems to promote local steroidogenesis by directly inducing steroidogenic enzymes in intestinal epithelial cells. Therapeutic administration of TNF induces GC synthesis in oxazolone-induced colitis and ameliorates intestinal inflammation, whereas inhibition of intestinal GC synthesis abrogates the therapeutic effect of TNF. These data show that TNF suppresses the pathogenesis of acute intestinal inflammation by promoting local steroidogenesis.
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