title: Prdx6 Deficiency Ameliorates DSS Colitis: Relevance of Compensatory Antioxidant Mechanisms.
abstract: OBJECTIVE
  An imbalance between cellular antioxidant defence system[s] and reactive oxygen species [ROS]-driven oxidative stress has been implicated in the pathogenesis of inflammatory bowel disease. Peroxiredoxin [PRDX] 6 contributes to an appropriate redox balance by clearing ROS and reducing peroxidized membrane phospholipids. We here studied the role of PRDX6 in acute and chronic dextran sodium sulphate [DSS]-induced colitis.
  
  
  METHODS
  To investigate the impact of PRDX6 on intestinal inflammation, we used wild type [WT], Prdx6 knock-out mice [Prdx6-/-] and transgenic mice [Prdx6tg/tg], overexpressing Prdx6. Acute and chronic colitis was induced by DSS in WT, Prdx6-/- and Prdx6tg/tg mice. Colitis was evaluated by endoscopy, colon length, histopathological assessment and myeloperoxidase [MPO] activity. Changes in mRNA and protein expression of pro-inflammatory cytokines and antioxidant enzymes were evaluated by real-time quantitative polymerase chain reaction [RT-qPCR] and western blot. Total glutathione [GSH] levels in colon samples were determined.
  
  
  RESULTS
  Prdx6-/- mice exposed to acute and chronic DSS showed a significant decrease in the clinical parameters and in colonic expression of pro-inflammatory cytokines compared with WT mice. mRNA expression of antioxidant enzymes in colon samples was significantly increased in Prdx6-/- compared with WT mice exposed to acute and chronic DSS. In addition, total GSH levels were increased in Prdx6-/- mice treated with DSS in comparison with WT. Overexpression of Prdx6 did not significantly influence acute and chronic colitis.
  
  
  CONCLUSIONS
  Our data indicate that a lack of the antioxidant enzyme PRDX6 protects against the development of acute and chronic experimental colitis and is associated with increased expression and function of other antioxidant enzymes, suggesting effective compensatory mechanisms.
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich,Zurich, Switzerland.
authors.forename: Hassan
authors.initials: H
authors.lastname: Melhem
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich,Zurich, Switzerland.
authors.forename: Marianne R
authors.initials: MR
authors.lastname: Spalinger
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich,Zurich, Switzerland.
authors.forename: Jesus
authors.initials: J
authors.lastname: Cosin-Roger
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich,Zurich, Switzerland.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Atrott
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich,Zurich, Switzerland.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lang
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich,Zurich, Switzerland.
authors.forename: Kacper A
authors.initials: KA
authors.lastname: Wojtal
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.|Division of Gastroenterology and Hepatology, Triemli Hospital, Zurich, Switzerland.|Zurich Center for Integrative Human Physiology [ZIHP], University of Zurich, Zurich, Switzerland.
authors.forename: Stephan R
authors.initials: SR
authors.lastname: Vavricka
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.|Division of Gastroenterology and Hepatology, Triemli Hospital, Zurich, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.affiliation: Department of Gastroenterology and Hepatology, University Hospital Zurich, Zurich, Switzerland.|Division of Gastroenterology and Hepatology, Triemli Hospital, Zurich, Switzerland.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Frey-Wagner
mesh_terms: D000208:Acute Disease; D000818:Animals; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D003106:Colon / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D016264:Dextran Sulfate; D016099:Endoscopy, Gastrointestinal; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D005981:Glutathione Synthase / Q000235:genetics; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D061105:Peroxiredoxin III / Q000235:genetics; D054465:Peroxiredoxin VI / Q000235:genetics* / Q000378:metabolism; D054464:Peroxiredoxins / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D016207:Cytokines; C000611649:IFNG protein, mouse; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; C516116:Prdx3 protein, mouse; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D007371:Interferon-gamma; D016264:Dextran Sulfate; C515977:PRDX6 protein, human; D061105:Peroxiredoxin III; D054465:Peroxiredoxin VI; D054464:Peroxiredoxins; C515981:Prdx4 protein, mouse; C515983:Prdx6 protein, mouse; D009195:Peroxidase; D052247:Nitric Oxide Synthase Type II; C560749:GCLM protein, mouse; D005721:Glutamate-Cysteine Ligase; D005981:Glutathione Synthase; D005978:Glutathione
keywords: IBD; Prdx6; ROS; antioxidant enzymes; colitis