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.
Elrod
John W
JW
Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center, Shreveport, 71130, USA.
Laroux
F Stephen
FS
Houghton
Jeffrey
J
Carpenter
April
A
Ando
Tomoaki
T
Jennings
Merilyn H
MH
Grisham
Matt
M
Walker
Nicole
N
Alexander
J Steven
JS
D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007371:Interferon-gamma / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009566:Nitrates / Q000097:blood; D052247:Nitric Oxide Synthase Type II / Q000097:blood; D009573:Nitrites / Q000097:blood; D050800:STAT6 Transcription Factor / Q000502:physiology*; D012720:Severity of Illness Index
D009566:Nitrates; D009573:Nitrites; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D007371:Interferon-gamma; D016264:Dextran Sulfate; D052247:Nitric Oxide Synthase Type II