原创力文档selective non-steroidal glucocorticoid receptor agonists attenuate inflammation but do not impair intestinal epithelial cell restitution in vitro选择性非甾体类糖皮质激素受体受体激动剂减弱炎症但不损害肠道上皮细胞体外归还.pdfVIP
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selective non-steroidal glucocorticoid receptor agonists attenuate inflammation but do not impair intestinal epithelial cell restitution in vitro选择性非甾体类糖皮质激素受体受体激动剂减弱炎症但不损害肠道上皮细胞体外归还
Selective Non-Steroidal Glucocorticoid Receptor
Agonists Attenuate Inflammation but Do Not Impair
Intestinal Epithelial Cell Restitution In Vitro
1 1 2 1 ¨ 1,3,4
Kerstin C. Reuter , Stefan M. Loitsch , Axel U. Dignass , Dieter Steinhilber , Jurgen Stein *
1 Institute of Pharmaceutical Chemistry, Goethe University Frankfurt/Main, Campus Riedberg, Frankfurt/Main, Germany, 2 Department of Medicine I, Markus Hospital,
Frankfurt/Main, Germany, 3 Department of Internal Medicine, Elisabethen Hospital, Frankfurt/Main, Germany, 4 Crohn Colitis Centrum Frankfurt, Frankfurt/Main, Germany
Abstract
Introduction: Despite the excellent anti-inflammatory and immunosuppressive action of glucocorticoids (GCs), their use for
the treatment of inflammatory bowel disease (IBD) still carries significant risks in terms of frequently occurring severe side
effects, such as the impairment of intestinal tissue repair. The recently-introduced selective glucocorticoid receptor (GR)
agonists (SEGRAs) offer anti-inflammatory action comparable to that of common GCs, but with a reduced side effect profile.
Methods: The in vitro effects of the non-steroidal SEGRAs Compound A (CpdA) and ZK216348, were investigated in
intestinal epithelial cells and compared to those of Dexamethasone (Dex). GR translocation was shown by
immunfluorescence and Western blot analysis. Trans-repressive effects were studied by means of NF-kB/p65 activity and
IL-8 levels, trans-activation potency by reporter gene assay. Flow cytometry was used to assess apoptosis of cells exposed to
SEGRAs. The effects on IEC-6 and HaCaT cell restitution were determined using an in vitro wound
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