TNF suppresses acute intestinal inflammation by inducing local glucocorticoid synthesis.
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.
Noti
Mario
M
Division of Experimental Pathology, Institute of Pathology, University of Bern, 3010 Bern, Switzerland.
Corazza
Nadia
N
Mueller
Christoph
C
Berger
Barbara
B
Brunner
Thomas
T
D000818:Animals; D003424:Crohn Disease / Q000517:prevention & control; D004195:Disease Models, Animal; D005938:Glucocorticoids / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control*; D015212:Inflammatory Bowel Diseases / Q000517:prevention & control; D007410:Intestinal Diseases / Q000378:metabolism / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005938:Glucocorticoids; D014409:Tumor Necrosis Factor-alpha