PWE-110 A Role For Peroxiredoxin-4 In A Murine Colitis Model Of Intestinal Inflammation.

Authors:
S Pfeuffer, N Trost, K Aden, S Schreiber, S Lipinski, P Rosenstiel
Year of publication:
2014
Volume:
63 Suppl 1
Issue:
-
Issn:
0017-5749
Journal title abbreviated:
GUT
Journal title long:
Gut : journal of the British Society of Gastroenterology
Impact factor:
14.921
Abstract:
We found that during DSS-induced colitis Prdx4 (-/-) mice lost significantly more weight and had a more pronounced disease activity than their wild-type littermates. However, no such differences were observed in Prdx4 (ΔIEC/ΔIEC) mice, compared to their Prdx4 (floxed/floxed) littermates. Likewise, colon histopathology and endoscopy did not reveal significant differences. We next examined Prdx4 expression in dissociated intestinal segments and found that Prdx4 levels in the lamina propria exceeded those of the intestinal epithelium (foldchange >2). In addition, already under basal conditions, lamina propria immune cell composition differed significantly between Prdx4 (-/-) and wild-type mice.Peroxiredoxins are a family of highly conserved antioxidant proteins. Beside its role in the reduction of peroxides, Peroxiredoxin-4 (Prdx4) has been shown to play a role in the modulation of pro-inflammatory signalling cascades. Our group has previously demonstrated that Prdx4 is expressed in the intestinal mucosa and upregulated upon stimulation with the bacterial cell wall component muramyl-dipeptide (MDP). In addition, siRNA-mediated downregulation of Prdx4 increased MDP-induced NF-κB signalling. We therefore generated a murine Prdx4-knockout model to address the relevance of Prdx4 in the intestinal immune response in vivo .In this study, two different Prdx4-knockout mouse lines were used: A constitutive Prdx4(‑/-) knockout strain, in which global Prdx4 expression was deleted and a conditional mouse line that specifically lacked Prdx4 in the intestinal epithelium (Prdx4 (ΔIEC/ΔIEC)). Intestinal inflammation was induced by administration of dextran-sodium-sulfate (DSS) in the drinking water of Prdx4 (-/-), Prdx4 (ΔIEC/ΔIEC) and respective littermate control mice. Mice were assessed for weight loss, disease severity, histopathology and endoscopic appearance.Our data assign a protective role of Peroxiredoxin-4 in intestinal inflammation which does not arise from the intestinal epithelium but presumably from the lamina propria. Further studies will be needed to determine the functional basis and molecular mechanisms of the observed effects.None Declared.