Einleitung: Glukokortikoide (GC) sind, unter in Kaufnahme erheblicher Nebenwirkungen wie u.a. die Hemmung der Wundheilung, weiterhin die am häufigsten eingesetzten Substanzen in der Behandlung chronisch entzündlicher Darmerkrankungen (CED).

with a Limulus Amoebocyte Lysate assay; OVA absorption was detected by adoptive T-cell (DO11.10)transfer.RESULTS: Fasted mice gavaged with LPS absorbed 3-times more LPS into blood and MLN when subsequently gavaged with triolein (long-chain fat) than when gavaged with tributyrin (short-chain fat).Triolein-dependent absorption was abolished by an inhibitor of CM formation, Pluronic L-81.Absorbed LPS was associated with plasma CM remnants in LDL-R knockout mice suggesting that the LPS was secreted on chylomicrons.P38 MAPK phosphorylation in MLN lymphocytes was higher after gavage with triolein than with tributyrin, suggesting that LPS absorption resulted in lymphocyte activation.CaCo-2 cells pretreated with LPS secreted more LPS from cell-associated pools into the basolateral medium when stimulated with oleic acid than with butyric acid, and LPS secretion correlated with secretion of apolipoprotein B-48.Oleic acid-dependent LPS secretion by CaCo-2 cells was Pluronic L-81 sensitive.T84 cells, which do not secrete chylomicrons, did not secrete LPS upon incubation with oleic acid.Balb/C mice adoptively transfered with CFSE-labeled DO11.10 CD4 T-cells and subsequently gavaged with OVA and triolein had markedly more CFSE-labeled cells in MLN and spleen than mice gavaged with OVA and tributyrin; T-cell proliferation was also elevated.CONCLUSION: In this study we show that dietary fat affects the intestinal immune system by modulating absorption and MLN delivery of gut antigens.Fatty acids therefore may not only directly but also indirectly affect immune cells by modulating antigen absorption.

Einleitung: Kortikosteroide gelten, unter Inkaufnahme zahlreicher systemischer Nebenwirkungen, nach wie vor als hochwirksame Standardsubstanzen in der Therapie chronisch entzündlicher Darmerkrankungen (CED). Das bessere Verständnis deren transrepressiver und transaktivierender Eigenschaften führte zur Entwicklung neuer dissoziierter selektiver Glukokortikoid Rezeptor Agonisten (SEGRAs), mit deutlich geringerem Nebenwirkungsprofil bei erhaltener antiinflammatorischer Wirkung. Wir charakterisieren im Vergleich zu Dexamethason (Dex), den nicht-steroidalen, selektiven GR-Agonisten Compound A (CpdA; PNAS 2005) in vitro und in vivo, im Hinblick auf antiinflammatorische Potenz sowie sein Nebenwirkungsprofil an einem in vitro Wundheilungsmodel.