Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression

Biol Chem. 2003 Apr;384(4):597-607. doi: 10.1515/BC.2003.067.


Selenium-dependent glutathione peroxidase isoenzymes-1 and -2 are the major glutathione-dependent H2O2-reducing activities in the epithelium of the mid- to lower gastrointestinal tract. The two isoenzymes protect mice against ileocolitis. We have found that luminal microflora are required for colitis to develop in mice deficient in GPX-1 and GPX-2 activity (GPX-DKO). Within 7 days of association with microflora, previously asymptomatic germ-free GPX-DKO mice developed severe acute colitis while their littermates with at least one wild-type Gpx1 or Gpx2 gene remained virtually symptom-free. Microflora also affected Gpx2 gene expression. Gpx2, but not Gpx1, mRNA levels were elevated 4-5 fold in the ileum and colon in conventionally reared or microflora-associated adult mice compared with germ-free mice. Since the gastrointestinal tract microflora undergo major changes 2-3 weeks after birth, from relatively benign to a potentially stressful composition, we examined postnatal Gpx2 gene expression. The jejunal and ileal GPX-2 activity levels were low in two to three week-old mice and increased 5-7 fold during the next two weeks. GPX-2 activity levels were correlated with the mRNA levels. Colon Gpx2 mRNA levels held steady at about 50% of adult levels from 12-21 days of age but were several times higher than ileal levels. Our results suggest that ileal Gpx2 mRNA and GPX-2 activity levels are induced by luminal microflora. This response is consistent with a role for GPX as an anti-inflammatory activity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Aging / physiology
  • Animals
  • Antibodies / analysis
  • Colitis / enzymology*
  • Colitis / microbiology*
  • Colitis / pathology
  • Colon / microbiology
  • Colon / pathology
  • Gene Expression Regulation, Enzymologic / physiology*
  • Germ-Free Life
  • Glutathione Peroxidase / biosynthesis*
  • Glutathione Peroxidase / deficiency*
  • Glutathione Peroxidase / genetics
  • Ileum / growth & development
  • Ileum / microbiology
  • Ileum / pathology
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Selenium / metabolism*


  • Antibodies
  • RNA, Messenger
  • Gpx2 protein, mouse
  • Glutathione Peroxidase
  • Selenium