Metallothionein overexpression does not protect against inflammatory bowel disease in a murine colitis model.
BACKGROUND
We evaluated whether modulation of metallothionein (MT, and subsequent oxidative stress) would influence the development and progression of colitis.


METHODS
MT-transgenic (MT-TG), MT-knockout (MT-KO), and wild-type (WT) mice were treated with Dextran Sodium Sulfate (DSS) to induce colitis compared to controls (no DSS).


RESULTS
The DSS treated MT-TG and MT-KO mice responded in a manner similar to that of DSS treated WT mice, with all groups developing severe colitis. The colonic MT content in DSS treated animals increased drastically when compared to controls. The colonic and blood levels of the antioxidant, glutathione (GSH), were significantly reduced in DSS treated MT-TG and MT-KO mice. Howevei there was no significant difference in the cysteine levels in these mice. The subeellular level of MT was highest in intestinal crypts loci of MT-TG mice and was not observed in MT-KO mice as well as in the inflammatory lesions.


CONCLUSIONS
We conclude that MT does not appear to influence the development or progression of intestinal pathology in the DSS animal model of IBD.
Oz
Helieh S
HS
Department of Medicine, Division of Digestive Diseases and Nutrition, University of Kentucky Medical Center, Lexington, KY 40536, USA. helieh.oz@uky.edu
Chen
Theresa
T
de Villiers
Willem J S
WJ
McClain
Craig J
CJ
D000818:Animals; D003092:Colitis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D003106:Colon / Q000378:metabolism / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000473:pathology; D008668:Metallothionein / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic
D008668:Metallothionein; D016264:Dextran Sulfate