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

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.