DSS-induced colitis is exacerbated in STAT-6 knockout mice

Inflamm Bowel Dis. 2005 Oct;11(10):883-9. doi: 10.1097/01.mib.0000182871.76434.57.


Background: Several transcription factors have been proposed to regulate IBD including the signal transducer and activator of transcription-6 (STAT-6).

Methods: The role of STAT-6 was examined in the 5% dextran sulfate sodium (DSS)-induced murine model of colitis using STAT-6 and wildtype mice.

Results: The disease activity index (DAI) revealed a significant increase in DAI in STAT-6 mice over STAT-6 mice given DSS. Both STAT-6 and wildtype mice displayed severe inflammation and crypt damage. Additionally, STAT-6 mice showed significant injury to the proximal colon compared with their littermate controls. Furthermore, STAT-6 mice receiving DSS had dramatically higher levels of serum nitrite/nitrate than all other groups. STAT-6 animals also displayed higher levels of inteferon-gamma than wildtype mice.

Conclusions: Because STAT-6 has been reported to regulate the expression and activity of inducible NO synthase (iNOS), our data suggest that, in DSS colitis, STAT-6 may modulate iNOS, to limit NO formation and control the extent of inflammation in the colon. We conclude that STAT-6 may normally play an important regulatory role in the pathogenesis of inflammatory bowel disease, possibly through modulation of iNOS and interferon-gamma.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Colitis / chemically induced
  • Colitis / metabolism*
  • Colitis / pathology*
  • Dextran Sulfate
  • Disease Models, Animal
  • Interferon-gamma / blood
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Nitrates / blood
  • Nitric Oxide Synthase Type II / blood
  • Nitrites / blood
  • STAT6 Transcription Factor / physiology*
  • Severity of Illness Index


  • Nitrates
  • Nitrites
  • STAT6 Transcription Factor
  • Stat6 protein, mouse
  • Interferon-gamma
  • Dextran Sulfate
  • Nitric Oxide Synthase Type II