| First Author | Esworthy RS | Year | 2003 |
| Journal | Biol Chem | Volume | 384 |
| Issue | 4 | Pages | 597-607 |
| PubMed ID | 12751789 | Mgi Jnum | J:103116 |
| Mgi Id | MGI:3608474 | Doi | 10.1515/BC.2003.067 |
| Citation | Esworthy RS, et al. (2003) Microflora trigger colitis in mice deficient in selenium-dependent glutathione peroxidase and induce Gpx2 gene expression. Biol Chem 384(4):597-607 |
| abstractText | 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. |
